Abstract

Introduction: Thyroid nodules are frequently found in the general population, though malignancy is confirmed in only a minority of cases. Distinguishing between benign and malignant nodules before surgery is vital for appropriate clinical management. The utility of preoperative serum thyroglobulin (Tg) levels as a diagnostic marker in thyroid carcinomas remains controversial. This study aimed to provide a descriptive overview of patients with markedly elevated preoperative Tg levels (>500 ng/mL) and their corresponding histopathological outcomes.

Methods: A retrospective, single-center study was conducted at Smart Health Tower, which included patients who underwent surgical interventions for thyroid disorders between 2019 and 2025, with preoperative serum Tg levels exceeding 500 ng/mL. Patients were excluded if they had incomplete medical records. Patient demographics, clinical features, preoperative findings, surgical details, and final histopathology were retrieved from electronic medical records.

Results: A total of 260 patients were included, predominantly female (73.08%), with a median age of 49 years (QR: 38–61). Neck swelling was the most common symptom (63.08%). Ultrasonography showed follicular nodular disease in 60.0%. Fine-needle aspiration cytology revealed Bethesda II in 20.0%, IV in 13.85%, and VI in 11.15% of cases. Total thyroidectomy was performed in 74.62% of cases. Histopathology showed benign lesions in 70.77% and malignant lesions in 29.23% of the cases.

Conclusion: Preoperative Tg levels may be elevated in both benign and malignant thyroid disorders; however, Tg may not possess adequate diagnostic precision to be used as a sole indicator of malignancy.

Introduction

Thyroid nodules are highly prevalent in the general population, with ultrasonography identifying them in up to 60% of individuals. Despite their frequency, approximately 5% are malignant [1, 2].

Primary thyroid carcinoma is the most common endocrine malignancy and is broadly classified into follicular epithelial-derived and non-follicular epithelial-derived tumors. Tumors of follicular epithelial origin include differentiated thyroid carcinoma (DTC), poorly differentiated carcinoma, and undifferentiated (anaplastic) carcinoma. DTC, which encompasses papillary thyroid carcinoma (PTC), follicular thyroid carcinoma, and oncocytic (previously Hürthle), accounts for approximately 95% of all thyroid malignancies [3, 4].

Accurate preoperative identification of thyroid nodules as benign or malignant is essential for guiding appropriate treatment decisions [3]. Initial evaluation commonly involves thyroid ultrasound, which plays a vital role in differentiating benign from malignant nodules. Complementary diagnostic techniques, such as contrast-enhanced ultrasound and ultrasonic elastography, provide additional insight. Among these, ultrasound-guided fine needle aspiration (FNA) is considered the most reliable method for diagnosing DTC prior to surgery. However, the accuracy of both ultrasound and FNA can be affected by factors including nodule size, sonographic features, and the clinician’s experience [5].

Reliable serum biomarkers are also essential for diagnosing and managing DTC. Thyroglobulin (Tg), a large glycoprotein composed of 2750 amino acids with a molecular weight of approximately 330 kilodaltons, is synthesized and secreted by thyroid follicular epithelial cells. It is primarily localized within thyroid follicular structures, with only minimal quantities circulating in the bloodstream under normal physiological conditions [6]. In patients with DTC who have undergone total thyroidectomy, particularly those who receive radioactive iodine (I-131) therapy, serum Tg functions as a valuable biomarker for assessing residual thyroid tissue, disease recurrence, and distant metastases, as its presence in the circulation postoperatively is typically indicative of persistent or recurrent disease [3].

The clinical significance of preoperative Tg levels as a diagnostic and prognostic tool in thyroid carcinomas remains a subject of ongoing debate [3]. This study aimed to provide a descriptive overview of patients with markedly elevated preoperative Tg levels (>500 ng/mL, reference range 3–40 ng/mL) and their corresponding histopathological findings following thyroid surgery. All references were evaluated for eligibility using reputable predatory journal lists to ensure scholarly integrity [7].

Methods

Study Design

This retrospective, single-center study was conducted at the Smart Health Tower (Sulaymaniyah, Iraq) and included patients who underwent surgical interventions for thyroid disorders between 2019 and 2025. The study received approval from the Kscien Organization’s Ethics Committee under registration number 40 in 2025.

Inclusion Criteria

The study included only patients who had elevated preoperative serum Tg levels exceeding 500 ng/mL. The threshold of 500 ng/mL was selected because it represents a markedly abnormal elevation well beyond the ranges commonly reported in both benign and malignant thyroid disease in previous studies [8–14]. In addition, this value corresponded to the upper reporting limit of our institutional laboratory assay, which does not quantify Tg concentrations above 500 ng/mL.

Exclusion Criteria

Patients were excluded if they had incomplete medical records.

Data Collection

Demographic and clinical data were retrieved from electronic medical records. The variables collected included age, sex, occupation, relevant medical history, presenting symptoms, results of preoperative imaging and laboratory investigations, Bethesda category, type of surgery performed, and final histopathological diagnosis.

Statistical Analysis

All collected data were entered into Microsoft Excel and subsequently analyzed using IBM SPSS (Statistical Package for the Social Sciences), version 27.0. Continuous variables were presented as means with standard deviations or medians with quartile ranges, as appropriate, while categorical variables were summarized using frequencies and percentages.

Results

Patient Demographics

A total of 260 patients were included in this study. The majority were female (n = 190, 73.08%), while the remaining 70 patients (26.92%) were male. The median age was 49 years (QR: 38–61). The highest frequency of patients was observed in the 40–49 age group (n = 61, 23.46%), followed by the 50–59 age group (n = 53, 20.38%). In terms of smoking, 216 patients (83.08%) were non-smokers. The most common occupation among the patients was homemaker (n = 150, 57.69%) (Table 1).

Medical and Surgical History

Two hundred forty-three patients (93.46%) had no past medical conditions. Hypertension was present in 13 patients (5.0%). Most patients (n = 238, 91.54%) had no prior surgical history. Nineteen patients (7.30%) had previously undergone total thyroidectomy, and 2 (0.77%) had undergone right thyroid lobectomy (Table 1).

Presenting Symptoms and Laboratory Findings

The most common presenting symptom was neck swelling, reported in 164 patients (63.08%), while 76 patients (29.23%) were asymptomatic. All patients had preoperative elevated serum Tg levels exceeding 500 ng/mL. Thyroid-stimulating hormone (TSH) levels were within the normal range in 178 patients (68.46%) (Table 2).

Ultrasonographic and Fine-Needle Aspiration Findings

Ultrasonographic evaluation revealed thyroid follicular nodular disease (TFND) in 156 patients (60.0%), right thyroid lobe nodules in 44 (16.92%), and left lobe nodules in 32 (12.31%). According to the TI-RADS classification, most nodules were TR3 (n = 172, 66.15%), followed by TR4 (n = 53, 20.38%) and TR5 (n = 22, 8.46%). FNA findings based on the Bethesda system were available for 141 patients (54.23%). The most frequent categories were Bethesda II (n = 52, 20.0%), Bethesda IV (n = 36, 13.85%), and Bethesda VI (n = 29, 11.15%) (Table 2).

Surgical Intervention

Surgical intervention consisted predominantly of total thyroidectomy (n = 194, 74.62%). Central neck dissection was performed in 18 patients (6.92%), while lateral neck dissection was carried out in 11 patients (4.23%) (Table 3).

Histopathological Findings

Histopathological analysis showed that the most common diagnosis was TFND (n = 115, 44.23%), followed by PTC in 56 patients (21.54%). Among PTC cases, the conventional variant was the most frequent (n = 38, 67.86%). Hyperplastic nodules were reported in 28 patients (10.77%), and adenomatoid nodules in 10 (3.85%). In total, 184 patients (70.77%) were diagnosed with benign pathology, whereas 76 patients (29.23%) were confirmed to have malignant disease (Table 3).

Discussion

The production of Tg is influenced by various internal physiological factors, such as hyperthyroidism due to Graves' disease, TSH levels, and the size of the thyroid gland and nodules [15]. Tg binds covalently to iodine and is stored in the follicular lumen until stimulated by TSH, which triggers its reabsorption into thyroid cells and its enzymatic breakdown into the active thyroid hormones, T3 and T4. These hormones are then released into the bloodstream and can be measured using peripheral blood assays. While T3 and T4 are the primary hormones secreted, small amounts of Tg also enter the circulation and can be detected at low levels in healthy individuals with normal thyroid function. However, in individuals with DTCs originating from follicular cells, Tg appears to be actively secreted [15].

Since Tg is produced solely by thyroid follicular cells, measuring its levels in the blood following a total thyroidectomy for thyroid cancer has become a standard approach for identifying persistent or recurrent disease. A serum Tg concentration of 1.0 ng/mL or higher is considered a highly reliable indicator of tumor recurrence [15].

Ultrasonography and FNA are primary diagnostic tools used to distinguish benign from malignant thyroid nodules before surgery. While FNA is commonly employed for this purpose, both methods have notable limitations, particularly in accurately differentiating benign from malignant follicular tumors [3]. As a result, approximately 20% to 30% of thyroid nodules still require surgical intervention to obtain a definitive pathological diagnosis following FNA [3]. The current study's findings support this observation, as FNA results were available for only about half of the patients (54.23%), and a substantial proportion of nodules, especially those classified as Bethesda category IV or VI, still required surgical confirmation.

Preoperative serum Tg levels are advantageous due to their convenience, rapid availability, and consistent reproducibility. However, their effectiveness in differentiating benign from malignant thyroid nodules before surgery has not been conclusively established. Despite this, many studies have investigated the potential of preoperative Tg levels for this purpose in diverse patient populations [3].

Several studies have demonstrated a significant association between elevated preoperative Tg levels and the presence of thyroid malignancy. Melik et al. (2022) prospectively measured Tg levels in 203 patients undergoing total thyroidectomy and found that patients with PTC had significantly higher Tg levels (105.05 ng/mL) compared to those with benign disease (76.80 ng/mL). A receiver operating characteristic analysis identified a cutoff value of 102 ng/mL, with the difference reaching statistical significance (P < 0.05) [8]. Similarly, Petric et al. (2012) observed higher preoperative Tg levels in PTC patients relative to those with benign nodules [9]. Jin et al. (2022) further supported this association in a cohort study that included 500 PTC patients, 376 with benign nodules, and 125 healthy controls. After excluding patients positive for Tg antibodies, they reported significantly higher Tg levels in PTC patients (42.87 ng/mL) compared to those with benign nodules (33.13 ng/mL) and healthy individuals (14.90 ng/mL), though the difference between the benign and healthy groups was not significant [10]. In the present study, PTC was the most prevalent subtype among malignant cases with thyroglobulin levels exceeding 500 ng/mL, accounting for 73.68% of such cases. The conventional variant was the most common among these, representing 67.86% of the PTC cases.

In a broader evaluation, Lu et al. (2024) conducted a systematic review and meta-analysis. They found that, among patients with indeterminate cytology and negative Tg antibodies, those with malignant nodules had significantly higher serum Tg levels than those with benign nodules (OR = 2.59, 95% CI: 1.59–4.21, P < 0.001) [3].

Conversely, several studies have reported the opposite trend, with lower preoperative Tg levels observed in patients with DTC compared to those with benign thyroid nodules. Zhang et al. (2022) analyzed 1,519 DTC cases and 571 benign cases, finding significantly lower Tg levels in the DTC group (15.7 ng/mL vs. 52.1 ng/mL, P < 0.001) [11]. Aydogu et al. (2023) similarly found that patients with benign nodules had higher Tg levels than those with DTC (85.0 ng/mL vs. 27.15 ng/mL, P < 0.001) [12]. Kang et al. (2022) reported consistent findings, noting lower average Tg levels in DTC patients (238 ± 77 ng/mL) compared to those with benign nodules (532 ± 97 ng/mL, P = 0.02) [13]. Patel et al. (2019) echoed this trend, with a median Tg level of 167.5 ng/mL in benign cases compared to 30.8 ng/mL in malignant ones (P < 0.001) [14].

The present study found that only 29.23% of the cases were diagnosed with thyroid malignancy, primarily PTC, while the majority (70.77%) had benign pathology, predominantly TFND. These results align with those of Zhang et al. [11], Aydogdu et al. [12], Kang et al. [13], and Patel et al. [14], highlighting the limited specificity of preoperative Tg in differentiating malignant from benign thyroid conditions. The high Tg levels observed in both malignant and benign cases suggest that, although Tg may provide supplementary information in certain clinical contexts, it lacks sufficient diagnostic accuracy to be relied upon as a standalone marker for malignancy in the preoperative setting. These findings support the conclusion that preoperative Tg testing alone is unreliable for distinguishing between benign and malignant thyroid nodules.

A key strength of the study is the inclusion of a relatively large sample size from a single tertiary center with standardized surgical and pathological protocols, ensuring consistency in data collection and analysis. Additionally, excluding cases with incomplete records enhanced data reliability, and comparing cytological, radiological, and histopathological findings enabled a comprehensive assessment.

However, several limitations should be acknowledged. The retrospective design inherently carries a risk of selection and information bias. As a single-center study, the findings may not be generalizable to other populations or institutions with differing referral patterns or laboratory assays. Furthermore, thyroglobulin levels above 500 ng/mL could not be quantified precisely due to the assay’s upper limit, which may have limited the ability to explore potential dose response relationships. Finally, the absence of long-term postoperative follow-up data precluded evaluation of the prognostic significance of preoperative thyroglobulin levels.

Conclusion

Preoperative Tg levels may be elevated in both benign and malignant thyroid disorders; however, Tg may not possess adequate diagnostic precision to be used as a sole indicator of malignancy.

Declarations

Conflicts of interest: The authors have no conflicts of interest to disclose.

Ethical approval: Ethical approval was obtained from the “Kscien Organization’s Ethics Committee under registration number 40 in 2025.

Consent for participation: Not applicable.

Consent for publication: Not applicable.

Funding: The present study received no financial support.

Acknowledgements: None to be declared.

Authors' contributions: FHK, HAN, and AMS: Major contributors to the conception and design of the study, supervision of the project, and drafting and critical revision of the manuscript for important intellectual content. SFA: Contributes to data analysis and interpretation and participates in manuscript revision. ReMA, RaMA, and AMA: Involve in study design and assist with initial drafting and revision of the manuscript. HOB, ROM, ANQ, SHH, AAQ, HAA, and BAA: Contribute to data acquisition and collection. All authors read and approved the final version of the manuscript and agree to be accountable for all aspects of the work.

Use of AI: ChatGPT-4.5 was used to assist with language refinement and improve the overall clarity of the manuscript. All content was thoroughly reviewed and approved by the authors, who bear full responsibility for the final version.

Data availability statement: Data are available from the corresponding author upon reasonable request.

Abstract

Introduction: Pilonidal sinus (PNS) typically arises in the sacrococcygeal region but can occasionally present in atypical locations, including the axilla, intermammary region, umbilicus, interdigital web, and neck, often leading to delayed diagnosis and suboptimal management. This study aims to examine clinical features, surgical management, and outcomes of PNS in these uncommon sites.

Methods: This retrospective case series was conducted at a single center over eight years and examined patients with extra-sacrococcygeal PNS confirmed by histopathology. Clinical, surgical, and follow-up data were retrieved from patient records.  Data were analyzed using SPSS 25.0 and presented as descriptive statistics (frequencies, percentages, means, and ranges).

Results: This study included 4 patients, with an equal sex distribution (2 females, 50%; 2 males, 50%) and a mean age of 24 years (range: 16–31). Presenting symptoms included discharge, itching, pain, redness, and mass formation. None had significant past medical history, and one patient (25%) had prior surgery at the same site. Affected sites were equally distributed: breast (25%), axilla (25%), penile (25%), and scalp (25%). All patients underwent surgical intervention, and histopathology revealed tracts lined with epidermis, surrounded by mixed inflammatory cells, foreign body giant cells, and hair shafts in granulation tissue. During the follow-up period (mean follow-up: 13.5 months), no recurrence was observed.

Conclusion: Atypical presentations of PNS, although rare, can occur in diverse anatomical regions. Surgical excision with primary closure might be an effective treatment approach, potentially leading to favorable clinical outcomes and a low recurrence rate.

Introduction

Pilonidal sinus (PNS) is a common inflammatory disorder that typically occurs in the natal cleft, resulting from hair penetration into the skin, forming a tract lined with granulation tissue, which may develop into a pus-filled cavity [1,2]. The condition was first described by Mayo in 1833, who identified a hair-containing cyst just below the coccyx. The term "pilonidal" was coined by Hodge in 1880 and is derived from its Latin roots. Despite being recognized for nearly two centuries, the pathogenesis of PNS remains a subject of ongoing debate [3]. Notable contributions by Karydakis and Bascom have shifted the understanding of PNS from a congenital neural tube abnormality to an acquired condition, emphasizing the role of environmental and lifestyle factors [4,5]. PNS risk factors include poor hygiene, a deep natal cleft, excessive hair growth, and a sedentary lifestyle. Although often asymptomatic, PNS may present as a recurrent abscess or a non-healing draining sinus [4]. The condition predominantly affects the sacrococcygeal area of hirsute males, with an estimated incidence of 26 per 100,000 people [6]. However, in rare cases, PNS can develop in atypical locations, including the axilla, intermammary region, umbilicus, interdigital webs, occiput, scalp, endoanal canal, groin, suprapubic area, clitoris, penis, and prepuce [2,3,7].

Given the scarcity of literature on atypical presentations of PNS, the current study aims to examine the clinical features and management of PNS in atypical locations (extra-sacrococcygeal). The eligibility of the references has been confirmed [8].

Methods

Study Design 

This retrospective case series was conducted over eight years at a single private facility, focusing on patients with atypical PNS who were evaluated, treated, and followed up. Ethical approval for this study was obtained from the Ethical Committee of the Kscien Organization (Approval No. 31/2025). Clinical, surgical, and follow-up data were collected through a systematic review of electronic medical records, surgical pathology reports, and consultation with treating healthcare providers when necessary. Informed consent was obtained from all patients or their guardians for the publication of their anonymized data.

Setting and Participants

The study included patients with atypical (extra-sacrococcygeal) PNS presentations who were admitted to the hospital during the study period. Clinical and sociodemographic data were collected from patient records. The following variables were recorded: age, gender, signs and symptoms, past medical and surgical history, clinical examination findings, ultrasound (US) findings, surgical indications, type of surgery performed, histopathological results, complications, and follow-up duration.

Inclusion and Exclusion Criteria

Eligible participants were those with confirmed PNS diagnoses through HPE. Patients with incomplete clinical or sociodemographic data or those whose diagnosis could not be confirmed through histopathology were excluded. Patients with primary sacrococcygeal PNS or those lacking follow-up data were also excluded from the study.

Surgical Management

All patients underwent thorough preoperative planning and assessments to evaluate their suitability for local anesthesia. Preoperative evaluations included US, monitoring of vital signs, viral screening, and hematological assessment, including a complete blood count and hemoglobin level measurement. Surgical procedures were performed with patients in the supine position. The surgical approach involved wide local excision of the PNS followed by primary closure. Following wide local excision, Salih’s preparation (a mixture of sclerosing agent and Lawsonia inermis) was applied to the wound bed and sinus margins prior to primary closure. This was performed to enhance wound healing and reduce the risk of infection [9]. Postoperative pain was managed with oral paracetamol at a dose of 1,000 mg, administered every 6–8 hours as needed, for a minimum of five days.

Statistical Analysis

The data were organized and analyzed using Microsoft Excel 2019. Descriptive analysis was conducted using the Statistical Package for Social Sciences (SPSS) version 25.0. The results are presented as frequencies, percentages, means, and ranges.

Results

Clinical and Histopathological Features

This study included four patients, comprising 2 females (50%) and 2 males (50%), with a mean age of 24 years (range: 16–31 years) (Table 1). Patients presented with various symptoms, including discharge, itching, pain, and erythema. None of the patients had significant past medical history.  One patient (25.0%) had a history of prior surgery at the same site. The affected sites varied, with the breast, axilla, penile, and scalp region each in one case (Figures 1 and 2). Ultrasound imaging was performed in three of four cases (75%), and the findings revealed simple breast cysts with associated midline and inframammary PNS, infected dermal–subdermal cysts with mild edema, and chronic PNS in the left temporal scalp region (Table 1). All patients underwent surgical intervention, including excision of sinuses or complete removal of masses/nodules. HPE revealed tracts lined with epidermis, surrounded by mixed inflammatory cells, foreign body giant cells, and hair shafts embedded in granulation tissue.

Outcomes and Follow-up

All 4 cases had favorable outcomes with no recurrence. Follow-up duration ranged from 1 month to 4 years, with the mean follow-up period being 13.5 months. No significant complications or adverse events occurred, and postoperative recovery was uneventful, with no need for further interventions.

Discussion

The pilonidal disease has a spectrum of clinical manifestations, ranging from asymptomatic to large, symptomatic abscesses. The exact cause of PNS remains unclear, with two main theories, acquired and congenital, offering potential explanations for its development. The formation of PNS generally requires three key factors: the presence of hair in the skin, a region of wrinkled skin (such as the natal cleft or a scar), and a combination of hormonal and hygiene-related factors [5]. This condition is less frequent before puberty and after the age of 40 years, likely due to the influence of sex hormones during these periods. It is also three times more common in males than females. Studies have shown that individuals who sit for prolonged periods and bathe less frequently are at a significantly higher risk of developing PNS, with a 219-fold increased risk compared to those without these risk factors [2,10]. Among the 11 cases reported in the literature, the mean patient age was 24.7 years (range: 16–39 years). The most commonly affected site was the breast (36.4%), followed by the auricle (27.3%), with single cases involving the endoanal, scalp, submental, and neck regions (each 9.1%). The sex distribution showed a slight male predominance, with 6 males (54.5%) and 5 females (45.5%) (Table 1) [2,3,7,10–17]. In line with these findings, the current case series included 4 patients with an equal sex distribution (2 males, 50%; 2 females, 50%) and a comparable mean age of 24 years (range: 16–31 years).

The differential diagnosis for atypical PNS includes a broad range of conditions, such as hernia, endometriosis, urachal cyst, pyogenic granuloma, epidermoid cyst, dermoid cyst, and infected sebaceous cyst. Clinical signs often include pain, warmth, and swelling, indicating inflammation. This condition is multifaceted, causing physical discomfort and emotional distress for those affected, leading to direct healthcare costs and indirect societal costs due to lost work hours [11,12]. Among the cases reviewed, the most common presenting symptom was discharge (9/11, 81.8%), followed by pain (3/11, 27.3%) and mass or nodule formation (2/11, 18.2%) [2,3,7,10–17]. In the current series, two (50%) presented with masses (intermammary and axillary), and two (50%) presented with discharge (perianal and scalp), with pruritus, erythema, painless presentation, and chronicity each observed in a single case (25%).

PNS is most commonly diagnosed based on the clinical presentation, with laboratory or radiologic investigations generally unnecessary [10]. However, US can reveal strands of hair associated with the lesion. Fine needle aspiration cytology can help to rule out a neoplastic process, particularly when the suspicion for PNS disease is low [10]. Ultrasonography was performed in only 2 of the 11 cases reviewed (18.2%). One case demonstrated a single fistulous tract extending into the anal canal, while another revealed a well-defined hyperechoic lesion suggestive of a dermoid cyst. In the remaining 9 cases (81.8%), ultrasound evaluation was not carried out [2,3,7,10–17]. In the current series, ultrasound was performed in three of four cases (75%). Findings included simple breast cysts with associated midline and inframammary PNS, infected dermal–subdermal cysts with mild edema, and chronic PNS in the left temporal scalp region

A variety of both surgical and non-surgical approaches are utilized in managing PNS. Surgical interventions include simple incision and drainage, marsupialization, open wound management, primary closure, and rhomboid excision followed by a Limberg flap. Non-surgical methods typically involve the injection of sclerosing and wound-enhancing agents into the sinus tract. Managing atypical PNS often necessitates more tailored approaches, such as resection with or without primary closure. Postoperative complications and recurrences are common, with significant risk factors identified, including obesity, a family history of PNS, male sex, tobacco use, inadequate hygiene, sinus size, and the specific surgical technique employed [3, 4]. The ideal management of PNS should aim to alleviate patient discomfort, reduce hospital stays, minimize recurrence rates, address complications, and limit prolonged work absences [4].

Furthermore, the treatment should be safe, effective, and free from adverse consequences. Surgical approaches, however, may not align with these optimal treatment goals, as they can result in discomfort and prolonged work absences. While surgery remains the recommended approach for atypical PNS, it also facilitates a definitive diagnosis through HPE. Shareef et al. conducted a study involving 12 female patients, all presenting with discharge lasting from four weeks to two years. Nine of these patients underwent resection with direct closure, without a flap, while the remaining three had their PNS excised and allowed to heal secondarily. Recurrence was observed in three of the patients [13-18]. Among the cases reviewed, excision of sinuses was the most commonly performed procedure (5/11, 45.5%), followed by complete excision (3/11, 27.3%). Fistulectomy, wide local excision, and mass excision were each performed in a single case (9.1%) [2,3,7,10–17]. In the current series, surgical management included excision of a single sinus in two cases (50%), complete excision in one case (25%), and excision of multiple sinuses in one case (25%). All 15 cases, including 11 reviewed in the literature and 4 from the current series, remained symptom-free with no recurrence during follow-up.

This study has several limitations. First, the retrospective design may introduce selection bias and limit the ability to establish causal relationships. Second, the small sample size limits the generalizability of the findings. Third, the follow-up period varied among the patients, which could affect the assessment of long-term outcomes. Finally, the study was conducted at a single center, which may not reflect the broader population.

Conclusion

This case series highlights the rare occurrence of PNS in atypical locations, with clinical and HPE findings that resemble typical cases. Surgical excision might result in favorable outcomes without recurrence.

Declarations

Conflicts of interest: The authors have no conflicts of interest to disclose.

Ethical approval: Ethical approval was obtained from the  Ethical  Committee  of  the  Kscien  Organization  (Approval  No. 31/2025)

Consent for participation: Not applicable.

Consent for publication: Informed consent was obtained from all patients or their guardians for the publication of their anonymized data.

Funding: The present study received no financial support.

Acknowledgements: None to be declared.

Authors' contributions: SL, HHK, DAI, and AMM: Major contributors to  the conception  of  the  study,  as  well  as  the  literature  search  for related  studies,  and manuscript  writing. KMS, SHH, KAN, HAA, AAQ and AMA: Literature review, critical revision of the manuscript, and processing of the tables and figures. All authors have read and approved the final version of the manuscript.

Use of AI: ChatGPT-4.5 was used to assist with language refinement and improve the overall clarity of the manuscript. All content was thoroughly reviewed and approved by the authors, who bear full responsibility for the final version.

Data availability statement: Not applicable.

Abstract

Introduction: Male breast cancer is a rare malignancy, and despite increasing its prevalence, little is known about its prognosis, and management continues to rely largely on guidelines developed for female breast cancer. This study presents a single-center experience focusing on the diagnosis, therapeutic strategies, and prognostic outcomes associated with male breast cancer.

Methods: The study was carried out between May 2020 and January 2025. All the male patients diagnosed with breast cancer were identified from the center's database. The study included those with complete medical records, encompassing demographics, clinical presentation, imaging findings, outcome, and follow-up data.

Results: Fifteen male breast cancer cases were analyzed (mean age 59.47 ± 12.97 years). The left breast was affected in 60%, and 80% presented with a painless lump. Tumor size ranged 0.6–5.4 cm (mean 2.53 ± 1.50 cm). Modified radical mastectomy was performed in 86.66%. Invasive ductal carcinoma predominated (93.33%), with lymph node involvement in 40% and bone metastasis in 6.67%. Immunohistochemistry results were available for 5 patients (33.33%); all of them were estrogen receptor and progesterone receptor positive and human epidermal growth factor receptor 2 negative. Adjuvant chemotherapy and radiotherapy were used in 33.33%, while 20% received triple modality therapy. Mean follow-up was 2.8 ± 1.52 years (range 1–5), with one recurrence.

Conclusion: Male breast cancer may present as a breast mass and is often diagnosed as invasive ductal carcinoma. Modified radical mastectomy accompanied by adjuvant therapy might offer favorable outcomes.

Introduction

Male breast cancer (MBC) is a rare condition, representing about 1% of all malignancies in men and of all breast cancer cases globally. Moreover, MBC accounts for less than 0.2% of cancer-related mortality among men. Breast cancer occurs less frequently in males, with a male-to-female ratio of approximately 1:100. This lower incidence is primarily attributed to the limited amount of breast tissue and differences in hormonal profiles between men and women [1-3]. Data from the Surveillance, Epidemiology, and End Results (SEER) program show an increase in male breast cancer incidence from 1.0 per 100,000 in the late 1970s to 1.2 per 100,000 in 2000–2004, with a median age at diagnosis of 67 years [2,4]. Like female patients, certain germline mutations increase the risk of breast and other cancers in men. Approximately 15% to 20% of men with breast cancer report a family history of breast or ovarian cancer, and around 10% carry a known hereditary mutation associated with breast cancer predisposition. BRCA2 is the gene most strongly associated with MBC, with affected individuals facing a lifetime risk ranging from 1% to 6%, higher than the approximate 0.1% risk in the general male population [4]. Additional genetic risk factors may contribute to the development of MBC, such as alterations in the ratio of estrogen to testosterone, as seen in individuals with Klinefelter syndrome [5]. Management of MBC is largely adapted from treatment protocols established for female breast cancer (FBC), owing to the limited availability of prospective, male-specific clinical trials. Notably, male patients represented only 0.087% of participants across 131 breast cancer clinical trials [6]. The current study presents a single-center experience regarding the diagnosis, management, and prognosis of MBC patients. All the references have been evaluated, and non-peer-reviewed sources have been excluded [7].

Methods

Study Design and Setting

This study was a single-center case series carried out at the Breast Clinic of Smart Health Tower between May 2020 and January 2025. This study was approved by the Ethics Committee of Kscien organization (Approval No. 2025-36).

Participants and Eligibility Criteria

The study included patients with a confirmed histopathological diagnosis of MBC who had complete medical records and provided consent for the publication of their data.

Data Collection

Data were retrieved from the hospital’s registry. The parameters included demographic details, clinical presentation, diagnostic findings, management, outcome, and follow-up.

Intervention

The patients underwent surgery under general anesthesia in the supine position, following skin preparation and antiseptic measures. The surgical approach was tailored to the specific requirements of each case, utilizing elliptical, Stewart, or alternative incision techniques as appropriate. After the incisions, procedures such as wide local excision, modified radical mastectomy (MRM), or nipple-areolar sparing mastectomy were performed. In all cases, the long thoracic and thoracodorsal nerves were preserved. Lymph node management involved either sampling or dissection of levels I, II, and III. Hemostasis was secured, and a Redivac drain was placed for each patient. Finally, the surgical site was closed in anatomical layers. For histopathology, 5-µm-thick tissue sections were fixed in 10% neutral buffered formalin at room temperature for 24 hours and subsequently embedded in paraffin. The slides were prepared and stained with hematoxylin and eosin (Bio Optica Co.) for 1–2 minutes at room temperature, then examined using a light microscope (Leica Microsystems GmbH).

Data Processing and Statistical Analysis

All collected data were recorded and organized using Microsoft Excel 2021. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS), version 25.0. Descriptive statistics were applied to summarize the results. Continuous variables were reported as means with standard deviations or medians with interquartile ranges, while categorical variables were presented as frequencies and percentages.

Results

Patient Demography

A total of 15  MBC cases were diagnosed and managed during the period of conducting the study. Ages ranged from 40 to 85 years (59.47 ± 12.97). All participants were manual workers. 1 patient (6.67%) was an active smoker, 1 (6.67%) was a passive smoker, and none reported alcohol consumption. The history of breast cancer was positive in 1 patient (6.67%) who had undergone mastectomy (Table 1).

Clinical Presentation and Diagnosis

The left side was involved in 9 patients (60%), while the right side was affected in 6 patients (40%). Clinical presentations included a painless breast lump in 12 patients (80%) and an axillary lump, breast discharge, and breast pain in each of the remaining patients (6.67%). Gynecomastia was present in 2 cases (13.33%). The duration of symptoms ranged from one week to two years, with a median of 0.69 (5.77) months. On ultrasonography, tumor sizes ranged from 0.6 cm to 5.4 cm, with a mean size of 2.53 ± 1.50 cm. Tumors were located centrally in 10 patients (66.66%), in the upper outer quadrant in 3 patients (20%), and in the upper inner quadrant and axilla each in 1 patient (6.67%) (Table 2). Mammography was performed for 5 patients (33.33%), all of whom had microcalcifications with variations in margin appearance (Figure 1). Computed tomography revealed lymphadenopathy in 5 (33.33%) patients (Figure 2).

Management and Outcome

Thirteen patients (86.66%) underwent MRM. Of these, 6 patients (40%) had MRM with axillary sampling only, while 7 patients (46.66%) underwent MRM combined with axillary lymph node dissection (ALND) at different levels (5 cases with ALND levels I and II, one with ALND levels I, II, and III, and one with ALND level I). One case (6.67%) underwent bilateral nipple-areola sparing mastectomy with radiotherapy and axillary sampling. Additionally, wide local excision with axillary sampling was performed in one patient (6.67%) (Figures 3-5). Histopathology confirmed invasive ductal carcinoma (IDC) in 14 cases (93.33%), either in isolation or in association with other pathological findings (Figure 6). Seven patients (46.67%) had grade II tumors, while six patients (40.0%) had grade III tumors. Regarding lymph node status, 9 patients (60.0%) had no evidence of lymph node involvement, whereas 6 patients (40.0%) showed varying degrees of lymphatic spread. Bone metastasis was recorded in one patient (6.67%). Immunohistochemistry results were available for 5 patients (33.33%); all of them were estrogen receptor and progesterone receptor positive and HER2 negative. Ki-67 proliferation index was reported in 3 patients (20%), with values ranging from 40% to 41%. The most used adjuvant therapy included a combination of chemotherapy and radiotherapy in 5 cases (33.33%), and a combination of chemotherapy, radiotherapy, and hormonal treatment in 3 cases (20%). The follow-up period ranged from 1 to 5 years (2.8 ± 1.52 years), and only one case of recurrence was reported (Table 3).

Discussion

Breast cancer in males accounts for <1% of all cancers and <1% of breast cancers, with higher incidence in North America and Israel, lowest in Thailand, and the highest European rates reported in Italy [8]. The mean age of diagnosis in this study was comparable to that reported in the literature [2,4]. Smoking and alcohol consumption were infrequent among the MBC patients. It has been suggested that alcohol consumption is not associated with an increased risk of MBC, while the role of smoking as a potential risk factor remains controversial [8]. However, a study of 53 MBCs by Herrero et al. observed that 77% of the patients were ex-smokers and 17% had a history of alcoholism [9]. Only one patient in the current series reported smoking.

In the current study, 6.67% of the patients reported a family history of breast cancer. Soliman and Hetnał reported that 7.7% of the patients had a positive family history of breast cancer, while Herrero et al. found that 23% of the patients had a family history of breast or ovarian cancer [9,10]. A study involving 152 MBCs and 304 FBC patients from 1990 to 2014 revealed that a positive family history was significantly more common in MBC cases compared to FBC (30.9% vs. 18.4%) [11].

Gynecomastia is a common condition present in 30–50% of healthy men. Although gynecomastia is not considered a usual risk factor, the issue is still controversial. Gynecomastia has been reported in 6–30% of MBC cases [12]. Two of the patients in the present study had gynecomastia, and both were diagnosed with IDC. In a study of 642 MBC patients, gynecomastia was associated with a significantly increased risk of developing breast cancer. Even after adjusting for multiple variables, the association remained strong [12].

In the current study, 60% of the cancers were located on the left side, while 40% were right-sided. Although the sample size is limited, this distribution is consistent with existing literature, which generally shows a slight predominance towards the left side.  In a large analysis, 4,190 MBC were diagnosed in the left breast versus 3,868 in the right breast, giving a laterality ratio of 1.08 (95% CI: 1.03–1.13) [13]. However, in a smaller sample-sized study by Ilhan et al., breast cancer was located almost equally on the right side in 11 (52.3%) cases and on the left side in 10 (47.7%) cases [12].

A breast mass was the most common presenting symptom (80%), consistent with previous findings [10,12]. Soliman and Hetnał [10] reported a 100% incidence of breast mass in 39 MBC cases, with axillary involvement in 30%, which was higher than that in the present study. Similarly, Ilhan et al. found breast mass in 85.7% of their 21 cases [13]. Nipple discharge was observed in 6.67% of cases, consistent with Ambareen et al., who reported a comparable incidence of 6% [2].

Initial diagnosis of MBC often occurs at a later stage than in FBC, and MBC often exhibits more advanced disease features, such as a larger tumor size [14]. Studies have reported mean sizes of 3.5, 2.4, and 6 [2, 7, 14]. The mean tumor size in the current study was 2.53 ± 1.50 cm, comparable to previous findings [2,8].

Regarding tumor location, MBC most commonly occurs in the subareolar region, whereas FBC typically presents in the upper-outer quadrant of the breast [8]. This pattern was also observed in the present study, with  66.66% showing centrally located tumors. Similarly, Ilhan et al. reported central tumor location in 90.4% of cases [12]. In contrast, Zhao et al. found a lower rate, with only 37.5% of tumors located centrally [11].

Approximately 90% of male breast malignancies are classified as IDCs, which are characteristically associated with elevated expression of hormone receptors. This biomolecular profile renders them highly amenable to hormone-based therapeutic interventions, often resulting in favorable clinical outcomes [15]. In contrast, invasive lobular carcinoma is exceedingly uncommon in the male population, primarily due to the absence of terminal ductal lobular units in the male breast. Its occurrence is typically restricted to individuals with increased exposure to endogenous or exogenous estrogens [14]. In the present study, 93.33% (14 of 15) of cases were IDC, either of the non-specific type or in conjunction with other histopathological subtypes.

In a case series on MBC, histological grade II was the most frequently reported, accounting for 54–58% of cases, followed by grade III (17–33%) and grade I (12–20%) [16]. The distribution of tumor grade in the current study generally aligns with these trends, but demonstrated a higher proportion of grade III tumors, highlighting the need for tailored treatment strategies and further investigation into the biological mechanisms underlying increased tumor aggressiveness in MBC.

Compared to FBC, MBC tends to present with higher lymph node involvement and distant metastases at the time of diagnosis [1]. In the present study, 60% of cases showed no evidence of lymph node involvement, whereas 40% exhibited varying degrees of lymphatic spread, and bone metastasis was recorded in one case. Similarly, Zhao et al. reported a nodal involvement rate of 44.1%. However, El Fouhi et al. reported a nodal involvement rate of 82% [11,15].

Typically, men with breast cancer are treated with MRM, often accompanied by ALND or sentinel lymph node biopsy. However, in selected cases, breast-conserving surgery, as well as nipple-sparing or skin-sparing mastectomies, may also be considered [14]. Performing ALND is linked to considerable postoperative morbidity, including lymphedema, infection, and sensory disturbances such as axillary paresthesia [17]. In the present study, thirteen patients (86.66%) underwent MRM, seven of whom (46.66%) underwent MRM accompanied by ALND, and one patient underwent nipple-areolar sparing mastectomy. This is comparable to a previous study in which 90% of MBC patients opted for MRM [1].

Chemotherapy regimens for MBC are comparable to those used in FBC [5]. In a prospective study conducted by the American National Cancer Institute between 1974 and 1988, involving 31 MBC patients with lymph node metastases treated with adjuvant chemotherapy, overall survival rates at 5, 10, and 20 years were reported as 80%, 65%, and 42%, respectively [5]. In the present study, nine patients (60%) received chemotherapy, either alone or in combination with other adjuvant therapies, with most achieving favorable outcomes during follow-up.

Given that over 90% of MBC cases are hormone receptor-positive, endocrine therapy plays a central role in treatment. Tamoxifen remains the most utilized anti-estrogen agent in both FBC and MBC management [17]. In the present study, immunohistochemistry
results were available for only five patients (33.3%), all of whom were hormone receptor positive and received tamoxifen. The apparent discrepancy with the higher rates reported in the literature likely reflects the absence of receptor status data for the remaining ten patients rather than a true difference in tumor biology.

Adjuvant radiotherapy is recommended for patients with axillary lymph node metastasis or who are undergoing breast-conserving surgery. Postoperative radiotherapy is also recommended for patients with tumors larger than 5 cm [5]. In the present study, 10 patients (66.67%) received radiotherapy, either alone or with other adjuvant therapies, with most achieving good outcomes during follow-up.

Management of MBC is controversial due to reliance on female-based data [6]. Key debates involve mastectomy versus breast-conserving therapy, unclear indications for radiotherapy, and the choice and duration of endocrine therapy (tamoxifen vs aromatase inhibitors ± GnRH analogues). The role of genomic assays in guiding chemotherapy, systemic therapy strategies in advanced disease, risks of under- or overtreatment, and psychosocial effects of radical surgery also remain unresolved [6].

Breast cancer in males exhibits distinct recurrence patterns influenced by tumor biology, stage, and treatment. In a cohort of 38 patients with estrogen receptor-positive, HER2-negative tumors, the distribution of the 21-gene recurrence score (RS) closely resembled that observed in FBC. Low RS (≤17) was found in 68.4% of cases, intermediate RS (18–30) in 23.7%, and high RS (≥31) in 7.9% [18]. According to a study, the rate of locoregional recurrence in MBC is approximately 10.1%, while distant recurrence has been reported in up to 21% of cases [18]. Only one case of recurrence was reported in the present study, after a median follow-up of 2.8 years.

This study had a few limitations. First, the follow-up periods were relatively short compared to other studies on the topic. Second, genetic testing and data on affected patients were lacking.

Conclusion

Male breast cancer may present as a breast mass and is often diagnosed as invasive ductal carcinoma. Modified radical mastectomy accompanied by adjuvant therapy might offer favorable outcomes.

Declarations

Conflicts of interest: The authors have no conflicts of interest to disclose.

Ethical approval: This study was approved by the Ethics Committee of Kscien organization (Approval No. 2025-36).

Consent for participation: Not applicable.

Consent for publication: Informed consent for publication was obtained from the patients.

Funding: The present study received no financial support.

Acknowledgements: None to be declared.

Authors' contributions: AMS, ROM, FHK, and MMA: Major contribution to the conception and design of the study, literature search, and manuscript drafting. HOB, SHS, HHF, NSS, HOA, SOA, and MKA: literature review, study design, data organization, table preparation, and critical revision of the manuscript. LRAP, FHF, AMA, RMA, and AHA: literature review and figure preparation. All authors have read and approved the final version of the manuscript.

Use of AI: ChatGPT-4.5 was used to assist with language refinement and improve the overall clarity of the manuscript. All content was thoroughly reviewed and approved by the authors, who bear full responsibility for the final version.

Data availability statement: Not applicable.

Abstract

Introduction: Cancer incidence and mortality are increasing worldwide, disproportionately affecting low- and middle-income countries due to limited healthcare access. This study aims to analyze the prevalence and clinicopathological characteristics of cancers diagnosed at a tertiary care center, offering crucial data to inform regional cancer control efforts.

Methods: This retrospective study was conducted at a single tertiary center, analyzing histopathological reports from January 2020 to January 2025. Data were collected from digital and physical archives by a trained team, including only confirmed malignant diagnoses. Variables extracted included patient demographics, cancer types, tumor characteristics, and procedure details. Data integrity was ensured through double-entry and expert review. Statistical analysis using SPSS 27.0 summarized categorical variables as frequencies, percentages and continuous variables as means or medians.

Results: A total of 9,375 cases were analyzed (median age 48 years), with females comprising 75.74% (7,101 cases). The age-standardized incidence rate was 82.20 per 100,000. Head and neck cancers accounted for 2,903 cases (30.97%), primarily thyroid (2,208 cases), followed by thoracic malignant tumors with 2,556 cases (27.26%). Invasive ductal carcinoma was most frequent cancer type (2,392 cases, 25.5%). Larger tumors correlated significantly with positive margins and lymph node involvement (p < 0.05).

Conclusion: The study highlights a unique cancer profile, with younger age at diagnosis and higher rates of head, neck, and thyroid cancers. These findings underscore the need for targeted screening and prevention strategies adapted to regional healthcare systems.

Introduction

Cancer remains one of the foremost causes of morbidity and mortality globally, representing a growing public health challenge of increasing magnitude and complexity. According to the International Agency for Research on Cancer, an estimated 20 million new cancer cases and 9.7 million cancer-related deaths were recorded worldwide in 2022 [1,2]. These figures underscore the profound global burden of cancer, with approximately one in five individuals developing the disease during their lifetime. Notably, one in nine men and one in twelve women are estimated to die from cancer [3].

Projections indicate that by 2070, the global incidence of cancer will surpass 34 million new cases annually, with lower-income countries experiencing a disproportionate impact marked by an anticipated 400% increase in cancer incidence over the next five decades [4]. Among the malignancies expected to contribute most significantly to this rise are breast, lung, and colorectal cancers. Current epidemiological models forecast that colorectal cancer cases will increase from 1.9 million in 2020 to 3.2 million by 2040, while breast cancer incidence is projected to reach a similar level by 2050, rising from 2.26 million cases in 2020 [5,6].

Substantial disparities in cancer burden are evident across countries with different income levels and health system capacities. In high-income nations, rising incidence rates of breast and thyroid cancers have been partially attributed to improved access to healthcare services and widespread implementation of early detection and screening programs [7]. Conversely, low- and middle-income countries tend to report higher incidence rates of cancers associated with infectious etiologies, such as cervical and liver cancers. These regions also face significantly higher cancer mortality rates, largely due to limited access to preventive services, early diagnosis, and effective treatment options [8,9]. Furthermore, marked differences in mortality-to-incidence ratios are observed across human development index categories. Data from Globocan 2020 indicate that mortality-to-incidence ratios are nearly twice as high in low- human development index countries compared to very high- human development index countries, 0.75 versus 0.36 for men, and 0.69 versus 0.30 for women [10].

Given the magnitude of the global cancer burden and the critical role of accurate epidemiological data in informing cancer control strategies, institution-level studies are essential. The current study aims to evaluate the prevalence and clinicopathological characteristics of cancers diagnosed via histopathological examination at a tertiary care center. By analyzing cases over a five-year period, this study seeks to provide insights into the local cancer profile, and identify the most frequently diagnosed cancer types. All referenced data sources have been verified for eligibility [11].

Methods

Study Design and Setting

This retrospective study was conducted at Smart Health Tower, Iraq. All histopathological reports issued between January 2020 and January 2025, were considered for inclusion.

Data Collection

Data were retrieved from both the digital and physical archives of the pathology department. A team of more than ten trained individuals participated in the collection process to ensure completeness and accuracy. Only reports that provided complete documentation of the required parameters were included in the analysis.

Inclusion and Exclusion Criteria

All histopathological reports confirming a malignant diagnosis and issued within the specified time frame were included in the study. Reports were excluded if they lacked a definitive diagnosis of cancer, were incomplete, or were duplicates.

Variables and Data Extraction

The following variables were extracted from each eligible report: patient age at diagnosis, sex, nationality, anatomical location of the lesion, cancer type, definitive diagnostic approach (histology, cytology, or immunohistochemistry), resection margin status (free or involved), tumor size in millimeters, and lymph node involvement (present or absent). All variables were systematically documented in a structured database for analysis.

Data Quality and Management

To maintain data integrity, a double-entry process was implemented. Two independent researchers entered the data separately, and any discrepancies between entries were resolved by reviewing the original reports. Only de-identified data were used.

Ethical Considerations

As this study involved retrospective analysis of anonymized medical records, the requirement for informed consent was waived. Confidentiality and data protection standards were strictly followed throughout the study. Ethical approval was obtained from the Kscien Organization (Approval No. 41/2025).

Statistical Analysis

Data analysis was performed using SPSS (Statistical Package for the Social Sciences) software (version 27.0). Descriptive statistics were used to summarize the data. Categorical variables, such as sex, type of cancer, and the anatomical system or organ affected, were reported as frequencies and percentages. Continuous variables, including age and tumor size, were presented as means with standard deviations or medians with quartile ranges, depending on data distribution. Comparisons of tumor size between groups (e.g., free vs. positive resection margins, lymph node involvement vs. no involvement) were performed using the Mann–Whitney U test, as tumor size was not normally distributed. A p-value < 0.05 was considered statistically significant.

Results

A total of 9,375 patients were analyzed (median age: 48.0 years; QR: 39.0–60.0). The age-standardized incidence rate was 82.20 (411.01/5) per 100,000 population per year (Table 1). Cancer incidence per 100,000 population rose with age, from 10.08 in the 0–10 group to a peak of 1,803.04 in the 71–80 group (Figure 1). Females comprised the majority at 7,101(75.74%). Of all evaluated cases, 6,635 (70.8%) were diagnosed by histology, 2,016 (21.5%) by cytology, and 724 (7.7%) underwent additional immunohistochemical analysis. Lymph node involvement was identified in 25.0% of cases, while nodes were not sampled in 49.3%. Invasive ductal carcinoma was the most frequently diagnosed cancer at 2,392 (25.5%) cases, followed by papillary thyroid carcinoma at 1,186 (12.7%) cases and unspecified adenocarcinoma at 639 (6.8%) (Table 2).

Head and neck lesions were the single largest category (2,903 cases, 30.97%), followed by thoracic region (2,556 cases, 27.26%). Multi‐regional involvement was 17.30%, while abdominal (7.03%), pelvic (5.43%), extremity (upper 7.94%, lower 0.77%), axial skeleton (1.19%), and integumentary/soft tissue (2.11%) sites made up the rest (Table 3). Within the head and neck, the thyroid gland and associated lymph nodes constituted the majority of cases 2,208 (99.68%). In the thoracic region, the breast was the most frequently affected site 1,980 (77.5%), while the pulmonary system accounted for 468 cases (18.3%). Abdominal organs represented 659 cases (7.03%) (Table 3).

Among the diagnostic procedures, excisional and incisional biopsy was the most frequently performed (2,300 cases, 24.5%), followed by fine needle aspiration (1,247 cases, 13.3%) and core needle biopsy (1,222 cases, 13.0%). In contrast, therapeutic interventions included total thyroidectomy with or without lymph node dissection (1,492 cases, 15.9%), wide local excision alone (415 cases, 4.4%), wide local excision with lymph node dissection (385 cases, 4.1%), mastectomy with lymph node dissection (275 cases, 2.9%), and mastectomy without lymph node dissection (270 cases, 2.9%) (Table 4).

The median tumor size was 5.1 mm (QR 2.2–22.0 mm) in cases with free resection margins, compared to 8.5 mm (QR 4.0–17.0 mm) in cases with positive margins, with the difference being statistically significant (p < 0.001) (Figure 2). Patients with lymph node involvement had significantly larger tumor sizes (median: 5 mm, QR: 2.3–20 mm, mean: 13.4 mm) compared to those without lymph node involvement (median: 4 mm, QR: 1.5–15 mm, mean: 10.6 mm) (p = 0.018) (Figure 3).

Discussion

Despite advances in global cancer surveillance, accurately capturing the true burden of cancer survivorship remains challenging, particularly in low- and middle-income countries. Although survival data from these regions have expanded in recent years, they often lack sufficient granularity for effective local health planning and policy development [12]. Against this backdrop, the present study provides detailed institution-level prevalence data from a tertiary care center in Iraq, offering valuable insights into the demographic, epidemiological, and clinical characteristics of cancer patients in this setting.

Age is a well-established risk factor for cancer development [13]. In the present study, the median age at diagnosis was 48.0 years, reflecting an earlier onset compared with most Western populations. This pattern aligns with broader epidemiological data from the Middle East, where cancers tend to present one to two decades earlier than in Western countries. Comparable medians have been reported in Jordan (55–56 years) [14,15] and Palestine (55 years) [16], while in a study from Basra, Iraq, which analyzed 2,163 cancer cases in 2017, the mean age was 51.4 ± 19.6 years [17]. In contrast, data from the U.S. National Cancer Institute’s Surveillance, Epidemiology, and End results program indicate a median cancer diagnosis age of 67 years, with individual cancers occurring at even older ages, lung (71), prostate (68), colorectal (66), and breast (63 years) [18]. Peak cancer incidence in this study occurred in the 71–80 age group, with 1,803 per 100,000 population, indicating that age-related cancer burden is increasingly affecting Iraq’s population. This pattern is consistent with national cancer registry data, which report the highest incidence among individuals aged 70–79 years [19]. In high-income countries, peak incidence occurs at slightly older ages and higher rates, such as 2,500 per 100,000 in U.S. adults aged 80–84 years [20] or adults ≥75 years comprising 36% of new UK cases [21]. In this study, the declining pattern in cancer incidence observed after the age of 80 was likely due to competing mortality, whereby many elderly individuals die from other conditions before cancer can be diagnosed; diagnostic underestimation, as very old patients are less likely to undergo extensive investigations; and population structure, since the >80 group made up only 1.1% of the total population, making the rates more sensitive to small changes in case numbers.

The age-standardized incidence rate (ASR) in this study was 82.20 per 100,000 population, consistent with low- and middle-income country figures but lower than the 2022 global ASR of 198 per 100,000 [22]. Regional ASRs vary: high-incidence countries like Cyprus, Israel, and Turkey report 196–340 per 100,000, while Jordan reports moderate ASRs of 131–137 per 100,000 [23]. The overall Arab countries’ ASR is ~132 per 100,000 [22], whereas high-income nations may exceed 300 per 100,000, with Australia at ~468 per 100,000 [24]. The relatively low ASR in this study may reflect Iraq’s younger demographic, limited screening, underreporting, registry limitations.

In this single-center series, head and neck lesions constituted the largest category, with 2,903 cases (30.97%), followed by thoracic lesions with 2,556 cases (27.26%). This distribution differs markedly from national cancer trends. Iraqi registries consistently identify breast and lung cancers as the most common malignancies, with bladder cancer leading in men; notably, breast cancer alone accounted for 19.5% of all malignancies in 2012 [25]. Similarly, a nine-year study from Karbala found head and neck tumors to represent only 2.7% of cancers [26]. Globally, head and neck cancers rank among the ten most common malignancies, with around 900,000 new cases annually [26]. In the UK, they are the eighth most common cancer, comprising 3% of new cases (approximately 12,400 per year), with peak incidence between 60–64 years [21]. Since the early 1990s, incidence rates in the UK have risen by over 35%, with a nearly 47% increase among females [27, 28]. The unusually high proportion of head and neck lesions in this study most likely reflects referral patterns rather than the true population-based incidence.

The thoracic category represented the second most common group in the current series, accounting for 27.26% of cases. This pattern is consistent with Iraq’s known cancer burden, where breast cancer is the most prevalent malignancy among women, comprising approximately 19–34% of female cancers [25]. A study from the Basra Cancer Control Centre analyzing 2,163 cases also highlighted bladder and lung cancers as the leading malignancies among men [17]. National statistics further confirm breast and lung cancers as the two most common cancer types overall. The prominence of thoracic cases in the present study is therefore not unexpected. Globally, lung cancer remains a major health challenge, with an estimated 2.2 million new cases and 1.8 million deaths reported in 2020, making it the leading cause of cancer-related mortality worldwide. Recent data from the International Agency for Research on Cancer (2025) indicate that lung adenocarcinoma has become the predominant histological subtype, with rising incidence particularly among younger populations and females [29,30].

Cancers of the abdomen (7.03%) and pelvis (5.43%) were less frequent compared to global trends. Worldwide, colorectal cancer is among the top three cancers in incidence and mortality, comprising approximately 10% of global cancer cases [10]. The lower proportion in this dataset might reflect underdiagnosis, referral patterns, or differences in lifestyle factors like diet and obesity, which are known contributors to colorectal carcinogenesis [31]. Similarly, the relatively low prevalence of integumentary/soft tissue cancers (2.11%) is consistent with global data, where soft tissue sarcomas are rare, accounting for less than 1% of all cancers in developed countries [32].

Globally, thyroid cancer was the tenth most common malignancy in 2020, with about 586,000 new cases (≈3% of all cancers), predominantly affecting women [33]. In this study, however, thyroid cancer comprised nearly a quarter of cases, far exceeding regional expectations. For comparison, a Saudi tertiary center reported overall rate of 9%  (12% in women) [34], whereas Iraqi registry data from 2012 did not list thyroid as one of the leading sites [25]. Globocan 2020 ranked thyroid cancer as the second most common cancer in Iraqi women (5.8%) [10]. This unusually high proportion likely reflects referral bias, as the center specializes in endocrine disorders and thyroid surgery. Conversely, several major cancers were underrepresented. Lung, colorectal, bladder, liver, and prostate cancers each accounted for only 1–4% of cases, compared with much higher global and national figures. Worldwide, lung cancer alone contributed 12.4% of new cases in 2022 and remains the leading cause of cancer death [3], whereas it was only 4.13% (387/9,375) here. Colorectal cancer was 1.5% (98/9,375) compared to 9.6% globally and 6.2% in Iraq [3,10]. Similarly, rates for bladder (1.9%), liver (1.7%), and prostate (1.1%) were well below both global averages and Iraqi data [3,10]. These discrepancies again point to strong referral and selection factors rather than true incidence.

The predominance of invasive ductal carcinoma in this cohort is consistent with global epidemiology, as it remains the most common form of breast cancer, representing 70–80% of invasive cases [35–37]. In the United States alone, about 276,000 women are diagnosed annually, with most cases occurring in those over 50 years [36]. Invasive lobular carcinoma, the second most common subtype, accounted for 2.2% of cases here, similar to SEER data showing its position behind ductal carcinoma [38]. Long-term analyses indicate stable ductal carcinoma rates but increasing lobular and mixed ductal-lobular subtypes over recent decades [39]. Ductal carcinoma in situ, observed in 4.7% of cases, reflects the influence of screening programs, with contemporary data showing it accounts for 20–25% of newly diagnosed breast cancers in the U.S., largely mammography-detected [40].

Papillary thyroid carcinoma comprised 12.7% of cases, aligning with global trends of increasing thyroid cancer incidence. It constitutes about 84% of all thyroid cancers, with a 3:1 female predominance, and its incidence rose from 9.9 to 16.1 per 100,000 between 2003 and 2017 before stabilizing in recent years [41]. Revisions in diagnostic criteria, particularly reclassifying certain follicular variants as in situ tumors, have slowed reported growth. Regional data illustrate heterogeneity, with a study from Jordan reporting papillary carcinoma increases from 89.6% to 94% of thyroid cases [42]. Follicular and medullary thyroid carcinomas were less frequent but remain important subtypes with distinct epidemiological features; notably, follicular carcinoma incidence rose by over 30% between the 1980s and 2000s [43]. Skin cancers were also represented, with basal cell carcinoma (2.2%) and squamous cell carcinoma (1.5%). Basal cell carcinoma is the most common skin cancer globally, with steadily rising incidence over the past decades [44]. Squamous cell carcinoma shows wide geographic variation, with plateauing or declining rates in Australia, stable rates in the U.S., but increases in Europe [45]. Hodgkin lymphoma, comprising 0.7% of cases, remains rare but is the most common cancer among adolescents. Recent U.S. rates are 3.8 per 100,000 in men and 2.9 per 100,000 in women, with a modest overall decline since 2000 [46]. Globally, incidence varies, highest in Southern Europe and lowest in Eastern Asia, with rising trends in younger populations, females, and Asian countries [47]. Urothelial carcinoma (2.1%) reflects its role as the predominant bladder cancer subtype, comprising ~90% of cases. In the U.S., ~84,870 new bladder cancers are reported annually, with a 4:1 male predominance [48]. Upper tract urothelial carcinoma, while rare (~2 per 100,000), contributes 5–10% of urothelial malignancies [49].

Biopsy and diagnostic procedures constituted the overwhelming majority of interventions (53.42%, n=5,017), with incisional and excisional biopsy being the most common procedure (24.5%, n=2,300), followed by fine needle aspiration (13.3%, n=1,247) and core needle biopsy (13.0%, n=1,222). This pattern reflects the critical importance of tissue diagnosis in cancer management, consistent with international guidelines that emphasize histopathological confirmation as the cornerstone of cancer diagnosis [50]. The high frequency of fine needle aspiration biopsy aligns with Iraqi studies demonstrating its effectiveness, with reported sensitivity rates of 87.3-96% and specificity rates of 83-100% for breast lesions, making it a preferred initial diagnostic tool due to its minimal invasiveness and cost-effectiveness [51,52]. Studies from other Middle Eastern centers have similarly reported high utilization of fine needle aspiration and core needle biopsies, particularly for superficial lesions and thyroid nodules [53].

Thyroid surgery represented the second most common category (18.36%, n=1,733), with total thyroidectomy (with/without lymph node dissection) being the predominant procedure (15.9%). The preference for total thyroidectomy over thyroid lobectomy (1.5%) and isthmectomy (0.1%) aligns with international guidelines for differentiated thyroid cancer, particularly for tumors larger than 4 cm or those with aggressive histological features. The high frequency of total thyroidectomy in this series is consistent with the current trend toward more aggressive surgical management for thyroid cancer in developing countries, where patients often present at more advanced stages [54].

Breast surgery accounted for 8.20% of procedures, with mastectomy-related procedures representing 754 cases. The predominance of mastectomy over breast-conserving surgery reflects the pattern observed throughout Iraq, where modified radical mastectomy remains the standard approach for breast cancer treatment. Studies from the Kurdistan region of Iraq show that 60.2% of breast cancer patients undergo mastectomy compared to 39.8% receiving breast-conserving surgery, with the proportion of breast-conserving surgery slowly increasing from 36.3% in 2016 to 43.7% in 2021 [55]. This mastectomy preference contrasts with international trends in developed countries where breast-conserving surgery is increasingly favored for early-stage disease [56].

This study has several limitations. First, potential referral bias may affect the representativeness of the findings, as the unusually high proportion of head and neck and thyroid cancers likely reflects the center’s specialized role rather than true population-based cancer incidence. The five-year study period and single-center setting further limit the generalizability of the results to broader populations. Finally, the absence of survival data and cancer staging information restricts the ability to assess outcomes and prognosis within the studied population.

Conclusion

The study highlights a unique cancer profile, with younger age at diagnosis and higher rates of head, neck, and thyroid cancers. These findings underscore the need for targeted screening and prevention strategies adapted to regional healthcare systems and population risks.

Declarations

Conflicts of interest: The authors have no conflicts of interest to disclose.

Ethical approval: Ethical approval for this study was obtained from the Ethical Committee of Kscien Organization (Approval No. 41/2025).

Consent for participation: Not applicable.

Consent for publication: Not applicable.

Funding: The present study received no financial support.

Acknowledgements: None to be declared.

Authors' contributions: AMM, and FHK: Major contribution to the conception and design of the study, literature search, and manuscript drafting. ARA, DAH, FA, MSE, HSA, LQR, MAK, DGH and HHR: literature review, study design, data collection, and critical revision of the manuscript. BAA, and SJH: literature review, table and figure processing. All authors have read and approved the final version of the manuscript.

Use of AI: ChatGPT-4.5 was used to assist with language refinement and improve the overall clarity of the manuscript. All content was thoroughly reviewed and approved by the authors, who bear full responsibility for the final version.

Data availability statement: Data are available from the corresponding author upon reasonable request.