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Metastatic male breast cancer; Orofacial region; Submandibular glands; Diagnostic challenges; Hormone receptor-positive; Rare metastases

Introduction

Male breast cancer typically exhibits positivity for hormone receptors. A less favorable prognosis is associated with advanced stages at the time of diagnosis. This description includes a case of breast cancer metastasis to the submandibular glands in a 75-year-old Serbian male patient. Examination of masses in both submandibular glands indicated metastasis from breast cancer, leading to the successful operative removal of the tumor masses. Male breast cancer is infrequent compared to its female counterpart, and there is a common misconception that men are not susceptible to breast cancer. Despite the prevalence of breast tissue components in both genders, including fatty and fibrous tissues, nipples, ducts, and lobules, men possess a smaller amount of breast tissue. However, they can still develop breast cancer. Biologically, the hormonal influence in girls during puberty promotes breast growth, while in boys, it inhibits such growth, resulting in smaller breast tissue. Approximately 1 out of every 100 breast cancers diagnosed in the USA occurs in men, as reported by the CDC. The most common types of breast cancer in men mirror those in women, encompassing invasive ductal carcinoma, invasive lobular carcinoma, and ductal carcinoma in situ (DCIS) [1,2]. Ductal carcinomas, originating in the milk ducts, predominate among breast cancers in men. Breast cancer, a prevalent malignancy in women, is known to metastasize to bone, with approximately 3.6% of all breast cancers developing bone metastasis. While breast cancer typically serves as the primary source of oral cavity metastasis in women, such metastasis to the head and neck area is uncommon in men. The rarity of this occurrence can pose challenges in diagnosis for clinicians and pathologists. This report details a case in which breast cancer metastasized to the right and left submandibular glands, with the diagnosis confirmed postoperatively. To efficiently present the clinical case, we conducted a thorough literature search on male breast cancer in English using official literature sources and reference databases. The most recent search was conducted on October 23, 2022. An influential scientific article, "An Update on the General Features of Breast Cancer in Male Patients-A Literature Review" (published on June 26, 2022) by Sinziana Ionescu, Alin Codrut Nicolescu, Marian Marincas, Octavia-Luciana Madge, and Laurentiu Simion, served as a key reference for our exploration. Following the methodology outlined by the aforementioned authors, we executed an identical data search and found no significant statistical deviations. We express our gratitude to the authors for their valuable research.

Case Study

Presented here is a case of metastatic male breast cancer in a 75-year-old patient admitted to the Department of Neurotraumatology at the Emergency Center of the University Clinical Center of Serbia. The initial symptoms, beginning in May 2022, included difficulty swallowing, dry mouth, and poor appetite. In the early stages, the palpable tumor mass in the left breast was only mildly noticeable visually. Concurrently, the patient contracted COVID-19, during which the tumor in the submandibular glands exhibited expansive growth. During hospitalization, comprehensive diagnostic procedures were conducted. The patient provided an anamnesis revealing awareness of the left breast tumor for the past 10 years [3,4]. Despite the submandibular tumor mass being deemed inoperable by other physicians, we opted for surgical intervention. The operation, performed on September 23, 2022, involved complete removal of the tumor mass, which was subsequently sent for histopathological analysis along with perimandibular tissue. The procedure, lasting 7 hours, involved the collection of 750ml of fluid (blood, hydrogen, and physiological solution combined). Histopathological examination of the right submandibular region revealed tumor tissue infiltration in the soft tissues of the neck and submandibular gland, morphologically and immunohistochemically consistent with HPV-negative squamous cell carcinoma. Similar findings were observed in the perimandibular tissue on the right side. The left submandibular region and corresponding perimandibular tissue exhibited comparable infiltration by HPV-negative squamous cell carcinoma. Postoperative CT scans of the neck, chest, abdomen, and pelvis revealed a necrotically altered lymph node on the left side of the neck and signs of reactive lymphadenopathy in other neck regions. Additionally, a solid nodule in the lower lobe of the right lung raised suspicion of a secondary deposit. Scarring changes with calcifications were observed in the lung tips as a sequel of a past tubercular process. In the upper inner quadrant of the left breast, a distinct tumor change without infiltration of the pectoral muscle was noted, closely related to the artery, a side branch of the contralateral right mammary artery, measuring 48mm x 36mm. The patient was subsequently referred for further treatment at the Institute for Oncology and Radiology of the Republic of Serbia. The etiology of breast cancer involves a complex interplay of predisposition and environmental factors. In male breast cancer (MBC), individuals are often diagnosed at an advanced age, with the average age of diagnosis being 71 years [5,6]. Predisposition factors, including genetics and family history, are significant contributors to MBC risk. Similar to women, males with a first-or second-degree relative affected by breast cancer face an increased risk. Bevier et al. (2012) reported comparable relative risks (RR) when the father or mother was affected (RR = 1.73 and 1.74, respectively). However, females had a slightly higher risk when a brother was affected compared to a sister (RR = 2.48 and 1.39, respectively). A positive family history is not the sole genetic influence; individuals with BRCA mutations, particularly BRCA-2 carriers, exhibit a 6% increased risk, while BRCA-1 carriers have a 4% risk of developing MBC. Additional genetic disorders, including Klinefelter syndrome (47, XXY), Cowden syndrome (PTEN tumor suppressor gene), Li-Fraumeni syndrome (TP53), and Lynch syndrome (PALB2 and mismatch repair genes), have also been associated with elevated MBC risk. The estrogen to androgen ratio plays a crucial role in MBC etiology. Excess estrogen stimulation, as seen in Klinefelter syndrome, contributes to increased risk. Environmental factors such as obesity, marijuana use, hepatic dysfunction, thyroid disease, and estrogen-containing medications may alter these hormone ratios. Notably, environmental factors also impact MBC risk. Previous radiation therapy, particularly for gynecomastia treatment, has been identified as a potential risk factor, with a sevenfold increase in MBC risk. Certain professions, including those in steel and rolling mills, as well as occupations involving organic solvents like trichloroethylene, have also been associated with an elevated risk of MBC. Male breast cancer is a relatively uncommon malignancy, comprising about 1% of all breast cancer cases and exhibiting a ratio of 1 male case for every 100 female cases. In the broader context of male cancers, it constitutes approximately 0.5% of all cancer diagnoses in men, though concerns have arisen regarding an increase in its incidence over recent decades [7]. Several studies have explored potential contributors to the rising incidence, including factors like obesity, alcohol consumption, and dietary habits. However, specific dietary patterns linked to male breast cancer remain inconclusive due to a lack of concrete research and evidence [8]. Despite identified risk factors, a noteworthy proportion of individuals diagnosed with male breast cancer exhibit no identifiable predisposing conditions. Histopathology reveals that invasive ductal carcinoma is the most prevalent type, constituting around 90% of all male breast cancer cases. In terms of hormone expression, approximately 90% of male breast cancers express the estrogen receptor, while 81% express the progesterone receptor. Notably, the expression of these hormone receptors tends to be more prevalent in male breast cancer compared to its female counterpart. Literature reviews, such as the one conducted by Sinziana Ionescu et al., provide comprehensive information on common and uncommon histological types, along with their respective prognoses and clinical significance [9]. Studies by Shaaban AM and Fentiman indicate that male breast cancer commonly presents as grade 2 ductal carcinoma with no special subtype and frequently exhibits the luminal A phenotype, akin to postmenopausal breast cancer in women. Oncotype DX has demonstrated effectiveness in determining recurrence risk in select male breast cancer cases, as seen in studies by Cho. Additionally, the use of deep-learning algorithms, such as Lunit SCOPE, has shown promise in predicting recurrence risk and identifying patients who may benefit from adjuvant chemotherapy. Unlike the female breast, papillary lesions, including papillary in situ and invasive carcinomas, are not uncommon in the male breast. Zhong's review emphasizes the clinicopathological spectrum of papillary carcinomas, noting favorable prognoses for both invasive and noninvasive forms, as also reported by Avau [10-15]. Other less common tumor types in male breast cancer include medullary, papilloma, and lobular carcinomas. Ductal carcinoma in situ is infrequently diagnosed due to limited awareness and stigmas associated with male breast cancer, leading to delayed diagnoses and poorer outcomes for patients.

Discussion

Men typically visit the doctor for a check-up when they notice a painful lump in one of their breasts. Additional symptoms may include nipple retraction, nipple discharge, ulceration, and pain. The smaller size of male breasts makes it easier to precisely diagnose tumor masses compared to women, despite potential masking by gynecomastia. It's crucial to discuss the patient's family history of breast cancer, past medical history, profession, and any previous exposure to estrogen or radiation. Evaluation of male breast cancer involves a triple assessment, including clinical assessment, mammography or ultrasonography, and core biopsy. While mammography is effective with a sensitivity of 92% and a specificity of 90%, it may be limited due to size and volume differences in male breasts. Ultrasound-guided core biopsy provides the most definitive diagnosis, particularly over fine-needle aspiration. In the realm of oral cavity tumors, salivary gland tumors like adenoid cystic carcinoma, acinic cell carcinoma, and mucoepidermoid carcinoma are predominant. Metastasis to the head and neck region is uncommon, presenting challenges for maxillofacial surgeons, oral surgeons, otorhinolaryngology surgeons, and pathologists. Metastatic tumors vary by gender, with common primary sites being breasts, genitourinary or gynecologic sites, kidneys, and colorectum in women, and the lung, kidneys, liver, and prostate in men. Metastasis to the oral cavity often involves the jaw, mandible, or maxilla, with jawbone metastases being more challenging to detect. In oral soft tissues, the gingiva is a frequent site, and inflammation such as periodontitis may contribute to metastatic cell attraction.

A literature review emphasizes the rarity of breast metastases in the oral and maxillofacial region of male patients. Although exceedingly rare, clinicians must consider breast metastasis when evaluating oral nodules, especially in older patients with a history of malignancy. Metastases to the parotid gland, including breast cancer metastasis, are extremely rare. Malignant salivary tumors constitute a small percentage of all cancers, and metastatic cases are even rarer. The most common malignancies metastasizing to the parotid gland are tumors arising from the head and neck, while breast cancer metastasis to the submandibular gland is even more uncommon. Our clinical case report involves a 75-year-old male, the 16th recorded case of metastases to the submandibular glands originating from breast cancer. Unlike previous cases, this instance is bilateral. While metastatic tumors to major salivary glands are rare, they underscore the importance of considering diverse metastatic sites, even in the absence of typical clinical manifestations.

Conclusion

Acknowledgement

Not applicable.

Conflict of Interest

Author declares no conflict of interest.