Salivary gland-like tumors of the breast: Histopathologic and genetic features with clinical implications.

Salivary gland-like tumors of the breast are rare neoplasms that share morphologic, immunophenotypic, and/or genetic features with their salivary gland counterparts, highlighting a shared underlying histopathogenesis in most cases. Salivary gland-like carcinomas included in the World Health Organization classification of breast tumors are adenoid cystic carcinoma, secretory carcinoma, mucoepidermoid carcinoma, acinic cell carcinoma, and the exceedingly rare polymorphous adenocarcinoma. These carcinomas are usually triple negative for estrogen receptor and progesterone receptor expression and HER2 overexpression, yet generally have favorable prognosis, in contrast to high-grade triple negative carcinomas of no special type. On the other hand, a small subset, such as solid-basaloid adenoid cystic carcinoma, rare high-grade carcinomas, and those associated with transformation to other types of high-grade invasive carcinoma can behave more aggressively. Other salivary gland-like tumors of the breast, such as pleomorphic adenoma and adenomyoepithelioma, are usually benign but can rarely undergo malignant transformation. Although clinical experience with salivary gland-like breast tumors is overall limited, their recognition and accurate classification has important implications for prognosis and clinical management, especially to avoid overtreatment of salivary gland-like carcinomas. The identification of characteristic genetic alterations and/or immunohistochemical surrogates in many of these tumors has practical applications to establishing an accurate diagnosis and directing clinical management. This review highlights the histopathologic and genetic characteristics of salivary gland-like breast tumors and the implications of the diagnosis for current clinical management.

Clinical Behavior and Molecular Insights of Secretory Carcinoma of Salivary Glands, a Single Center Experience.

OBJECTIVE: the study aimed to characterize the novel entity referred to as secretory carcinoma of the salivary glands. METHODS: we comprehensively evaluated 150 patients afflicted by malignant salivary gland tumors who had been under treatment at the University of Verona. Inclusion criteria primarily focused on the availability of paraffin block materials and adequate follow-up data. Subsequently, we conducted a comprehensive Fluorescent In Situ Hybridization (FISH) analysis, utilizing probes targeting NTRK-3, MALM-2, EWRS-1, HER-2, MDM-2, and NTRK1-2. RESULTS: out of the initial cohort, 37 patients met the eligibility criteria for our study. We identified NTRK3 gene rearrangements in four patients (11%), two of whom had mucoepidermoid carcinoma, and the remaining two had acinic cell carcinoma. Notably, none of these patients had initially received a secretory carcinoma diagnosis. The primary treatment approach for all patients entailed surgical parotid gland resection. The overall survival (OS) for patients with NTRK3 rearrangements amounted to 78 months, with a corresponding progression-free survival (PFS) of 73 months. CONCLUSION: in summary, our case series suggests that secretory carcinomas exhibit a favorable clinical course and underscores the pivotal importance of distinguishing secretory carcinomas from other histological subtypes.

Unmasking the rarity of mammary analogue secretory carcinoma of the minor salivary gland - A case report.

INTRODUCTION: Mammary analogue secretory carcinoma (MASC) of the salivary gland was first described by Skálová et al. in 2010. It is often associated with a translocation, t(12;15)(p13;q25), which results in the fusion gene ETV6-NTRK3. Major salivary glands, primarily the parotid gland, are involved in 70 % of cases of MASC, while small salivary glands are involved in less than 25 % of cases. This report aims to consolidate in unveiling, diagnosing, and managing the rarity of MASC in the minor salivary gland and its existing knowledge and encourage new research on this increasingly important salivary gland malignancy. PRESENTATION OF THE CASE: A 27-year-old female reported with a complaint of swelling on the right cheek region of face since 10 weeks. On bimanual palpation, a soft lobulated mass was appreciated beneath the healthy mucosal layer. The radiographic image (orthopantomogram) showed no obvious calcified mass. An excisional biopsy was planned and performed under local anesthesia. Microscopic and immunohistochemistry confirmed the tumor to be a MASC of minor salivary gland. DISCUSSION: Due to their infrequency and multiplicity of histopathology, MASC presents difficulty in diagnosis. A key to determining diagnostic criteria for MASC is to study cellular morphology, cytoplasmic filament expression, and ultrastructural features of the tumor and apply this information to defining MASC. CONCLUSION: MASC is an important molecularly defined entity of the salivary gland with low-grade malignant potential. Correct diagnosis is essential for appropriate treatment and will help to provide better information about this potentially low-grade malignant salivary gland neoplasm.

Secretory Carcinoma of the Philtrum of the Upper Lip: A Case Study.

The parotid, submandibular, and sublingual salivary glands are the major salivary glands in the mouth. Cancers that arise in these glands are relatively uncommon, usually benign, and rarely metastasize. We present a unique case of a 17-year-old male diagnosed with high-grade secretory carcinoma of the salivary gland that was generally asymptomatic except for a persistent rash. The patient reported no significant past medical, family, or social history. A multidisciplinary team efficiently diagnosed and treated the cancer with histopathology, MRI, tumor excision, lymphadenectomy, and adjuvant treatment. Despite the rarity of the cancer, which was found in a high-grade regionally advanced disease, in an uncharacteristically young patient, the patient was effectively treated with adjuvant chemoradiotherapy without treatment-related complications.

Secretory Carcinoma of the Thyroid: A Case Report and Update of Literature.

Primary secretory carcinoma (SC) of the thyroid gland is a rare neoplasm, characterized by the presence of oncogenic ETV6::NTRK3 fusions, which are amenable to tropomyosin receptor kinase (TRK) inhibitor therapy. Despite its morphologic, immunophenotypic, and genetic similarities to SC of the salivary and mammary glands, diagnostic pitfalls may arise in differentiating from papillary thyroid carcinoma due to overlapping features such as papillary growth, nuclear irregularity, and variable expression of PAX8. Tumor misclassification may lead to delayed consideration of molecular testing and targeted therapy. A total of 13 cases of thyroid SC have been documented in the literature, indicating a tendency for advanced clinical presentation followed by a protracted clinical course, with most patients surviving until the end of the study period despite some experiencing recurrences. However, tumor-related mortality occurred in around 30% of cases, with the overall survival ranging from days to years, underscoring the variability in tumor behavior and the need for further research efforts. Among documented cases of thyroid SC, prognostic factors established for salivary SC have shown broad distributions, including a mitotic activity ranging from < 1 to 10 per 10 high-power fields and variable presence of necrosis, awaiting additional case experience to better elucidate their relevance in thyroid SC. We hereby present a 61-year-old female patient with widely metastatic thyroid SC treated with larotrectinib and provide an updated review of the literature on the molecular pathogenesis and clinicopathologic characteristics of this rare entity.

Salivary gland secretory carcinoma: A case presentation in minor salivary gland with review.

INTRODUCTION AND IMPORTANCE: Salivary gland secretory carcinoma (SGSC) represents a rare malignant tumor of the salivary glands. Despite being regarded as low-grade tumors, they may manifest with metastases and a high-grade aggressive clinical behaviour. The literature on this subject is limited, and there is currently no standardized approach to treatment. CASE REPORT: We report a rare case of SGSC in the palate of a 14-year-old female patient. The patient underwent excision, bilateral tonsillectomy and adjuvant radiotherapy. CLINICAL DISCUSSION: A critical review of the literature was conducted with the objective of analysing the cases of intraoral SGSC that have been previously reported. A total of 23 articles, published between 2010 and 2024, were identified as being directly pertinent to the review, resulting in a total of 58 patients being included. CONCLUSION: SGSC on the hard palate in a 14-year-old child is an exceedingly rare occurrence. These tumors can mimic other pathologies of the salivary glands clinically and microscopically, which can result in misdiagnosis and a delay in treatment.

Secretory Carcinoma of the Breast: Radiologic-Pathologic Correlation.

Secretory carcinoma is a rare, low-grade, special histological type of invasive breast carcinoma. Although it is the most common primary breast cancer in the pediatric population, most cases are diagnosed in adults, with a median age of 48 years (range 3 to 91 years). It most often presents as a painless and slowly growing palpable lump. Imaging findings are nonspecific. Secretory carcinomas have abundant periodic acid-Schiff positive intracytoplasmic and extracellular secretions on histopathology. Nearly all secretory carcinomas have mild to moderate nuclear pleomorphism with low mitotic activity. Over 80% (86/102) of secretory carcinomas display the translocation of t(12;15)(p13;q25), resulting in ETV6::NTRK3 gene fusion. Secretory carcinoma generally has an indolent course and has a better prognosis and overall survival than invasive breast carcinoma of no special type. A good prognosis is associated with age <20 years, tumor size <2 cm, and ≤3 axillary lymph node metastases. Metastases beyond the ipsilateral axillary lymph nodes are rare, with the most common sites involving the lung and liver. Except for the potential addition of targeted drug therapy for NTRK fusion-positive tumors, the treatment approach is otherwise similar to invasive breast carcinomas of similar receptor status.

Secretory carcinoma of the minor salivary gland: An in-depth case report.

A 56-year-old female was referred to our service for management of a malignant salivary gland neoplasm with compromised margins that had been biopsied previously at another service. The patient reported a twenty-year history of a lesion in the oral cavity with progressive and exuberant growth over the past two years, associated with local pain and dyspnea. Physical examination revealed an erythematous, ulcerated, and hemorrhagic lesion measuring approximately 3 cm on the left soft palate and tonsillar pillar. Computed tomography revealed an expansile lesion in the topography of the left soft palate, growing predominantly toward the lumen of the nasopharynx and partially invading the left wall of this region. The patient underwent surgery and histopathologic examination revealed an infiltrative and aggressive epithelial neoplasia with large vacuolated and eosinophilic cytoplasm, vesicular nuclei, and prominent nucleoli. The neoplastic cells were arranged in a solid, microcystic, tubular, and follicular pattern with eosinophilic luminal secretion. Mitotic figures were frequent and all margins were affected by the neoplasia. Morphologic and immunohistochemical features supported the diagnosis of secretory carcinoma, and the patient is currently being followed for further therapeutic intervention.

ETV6 Molecular Heterogeneity in Salivary Secretory Carcinoma: A Case Series Report and Literature Review.

BACKGROUND: ETV6 gene rearrangement is the molecular hallmark of secretory carcinoma (SC), however; the nature, frequency, and clinical implications of atypical ETV6 signal patterns by fluorescence in situ hybridization (FISH) has not yet been systematically evaluated in salivary gland neoplasms. METHODS: The clinical, histopathologic, immunohistochemical and molecular features of seven salivary SCs, including four cases with atypical ETV6 FISH patterns, were retrospectively analyzed along with a critical appraisal of the literature on unbalanced ETV6 break-apart in SCs. RESULTS: The patients were four males and three females (31-70 years-old). Five presented with a painless neck mass and two patients with recurrent disease had a history of a previously diagnosed acinic cell carcinoma of the buccal mucosa. Histologically, there were varied combinations of microcystic, papillary, tubular, and solid patterns. All tumors were diffusely positive for S100 and/or SOX10, while 2 cases also showed luminal DOG1 staining. Rearrangement of the ETV6 locus was confirmed in 5/7 cases, of which 3 cases showed classic break-apart signals, 1 case further demonstrated duplication of the ETV6 5`end and the other loss of one copy of ETV6. Two cases harbored ETV6 deletion without rearrangement. Two of the 4 cases with atypical ETV6 FISH patterns represented recurrent tumors, one with widespread skeletal muscle involvement, bone and lymphovascular invasion. Surgical treatment resulted in gross-total resection in all 7 cases, with a median follow up of 9.5 months post-surgery for primary (n = 3) and recurrent disease (n = 1). CONCLUSION: Duplication of the distal/telomeric ETV6 probe represented the most common (26/40; 65%) variant ETV6 break-apart FISH pattern in salivary SC reported in the literature and appears indicative of an aggressive clinical course.

Salivary Secretory Carcinoma in a Patient with Immature Ovary Teratoma.

Introduction: Secretory carcinoma, previously known as mammary analog secretory carcinoma, is a rare malignancy of salivary glands. It has a diversity of microscopic patterns and is similar to other salivary gland tumors. Case Report: This report presents the case of a 32-year-old female patient with a painless swelling of the upper lip and a history of recent surgery for an immature ovarian teratoma. The microscopic sections revealed a circumscribed neoplasm composed of macrocystic, papillary-cystic, and microcystic patterns with bland vesicular nuclei and vacuolated cytoplasm. Tumoral cells were strongly positive for mammaglobin, SOX10, GATA3, S-100, and vimentin. The diagnosis of salivary gland secretory carcinoma was made. After 22 months, there has been no recurrence. Conclusions: As secretory carcinoma is a relatively new entity, it is necessary to understand its characteristics. Although the overall incidence of second primary cancer in patients with salivary gland cancers is low, the possibility of its presence in such patients should be considered.

A tale of recurrent secretory carcinoma of submandibular gland in an adolescent male: A rare presentation of a rare tumor.

Mammary analogue secretory carcinoma (MASC) is a rare salivary gland tumor which shares its histologic, immunohistochemical, and genetic features with the secretory carcinoma (SC) of breast. In this case report, we describe a case of MASC in a young adolescent male with swelling in the right angle of mandible which is a relatively rare site to present along with its correlation of cytological, histological, and immunohistochemical features. A 16-year-old male came with the complaint of swelling in the right angle of mandible since 2 years. Contrast-enhanced computed tomography (CECT) neck revealed differential diagnosis of nerve sheath tumor, pleomorphic adenoma, and adenoid cystic neoplasm was kept, and subsequently fine-needle aspiration cytology (FNAC) was done. FNAC was done in which differential diagnosis of myoepithelial neoplasm, acinic cell carcinoma, and SC was given. Surgical excision was done followed by histopathological examination. Immunohistochemistry panel was also applied, and final diagnosis of SC was rendered. SC has distinct cytological, histological, and immunohistochemical features which should be recognized by the pathologists for the appropriate management of the patient.

Mastopexy for secretory carcinoma of breast in a young female: a case report.

Secretory carcinoma, a triple-negative benign tumor, is one of the rarest malignancies of the breast which rarely metastasizes. Surgical excision via lumpectomy or mastectomy is the mainstay of treatment, but in young patients, mastopexy can be a better option cosmetically. A 26-year-old woman presented with a lump in her right breast that, on ultrasonography, was revealed to be a multi lobulated solid lesion measuring 25 × 16 mm2 in the retro areolar region at a 4 o'clock position. It turned out to be secretory carcinoma of the breast in a tru-cut biopsy. Vertical Mastopexy was opted for the removal and simultaneous reconstruction of the breast, which was followed by adjuvant chemotherapy and radiotherapy. Vertical mastopexy showed that the tumor was removed, and the breast was restored to its original form simultaneously. This procedure gave better results clinically and cosmetically. The patient had an uneventful recovery and is on a regular follow-up.

Insights Into Pediatric Secretory Carcinoma of the Salivary Gland: A Case Report.

Secretory carcinoma of the salivary gland (SCSG) is a rare head and neck tumor in adults and exceptional at the pediatric age. Its varied histological subtypes and distinct clinical presentation pose diagnostic and therapeutic challenges. Therefore, standardized guidelines are of utmost importance for the care of these patients, especially in children. Here we present an 11-year-old male presented with a left cheek mass initially diagnosed as lipoma. A wide resection was performed and SCSG was revealed in the histopathologic and immunohistochemistry analysis. The presentation of this case provides valuable information on the diagnostic and therapeutic complexities of SCSG. It emphasizes the need for standardized guidelines and further research to optimize pediatric patient outcomes. Overall, this case report is a crucial resource for clinicians and researchers, highlighting the importance of interdisciplinary collaboration and early intervention in managing SCSG.

Secretory Carcinoma of the Breast: A Rare Entity With Favorable Prognosis.

Secretory breast carcinoma (SBC) is an extremely rare entity of breast cancer, which can affect all age groups. The diagnosis is based on the characteristic microscopic appearance, and despite the triple negativity or low hormone receptor positivity, SBC is generally characterized by a favorable prognosis. Due to the rarity of the disease, no clear consensus on optimal treatment is available. Nevertheless, conservative surgery or mastectomy is the main therapeutic option. The efficacy of chemotherapy, radiotherapy, and hormone therapy in this pathology has not been rigorously explored. We report the case of a 65-year-old woman with SBC treated with surgery and adjuvant radiotherapy, with a review of the literature.

Molecular Pathology of Thyroid Tumors: Old Problems and New Concepts.

The molecular signatures of many thyroid tumors have been uncovered. These discoveries have translated into clinical practice and are changing diagnostic and tumor classification paradigms. Here, the findings of recent studies are presented with special emphasis on how molecular insights are impacting the understating of RAS mutant thyroid nodules, Hürthel cell neoplasms, and unusual thyroid tumors, such as hyalinizing trabecular tumor, secretory carcinoma of the thyroid, and sclerosing mucoepidermoid carcinoma with eosinophilia. In addition, the utility of detecting actionable molecular alterations by immunohistochemistry in advanced and aggressive thyroid cancer is also discussed.

Diagnostic Utility of Expression Pattern of S100/Mammaglobin/SOX10/DOG 1 Immunohistochemistry in Differentiation of Secretory and Acinic Cell Carcinoma: A Systematic Review and Meta-Analysis.

Secretory carcinoma (SC) is a relatively new disease entity, separate from acinic cell carcinoma (AciCC), which frequently displays ETV6-NTRK3 gene fusion. However, the differences between SC and AciCC remain ambiguous. Genetic diversity makes its diagnosis complicated. In this regard combined expression of immunohistochemistry markers S100/Mammaglobin/SOX10 and DOG1 is need of the hour as alternative methodology. The current systematic review was to investigate the diagnostic utility of combined immunohistochemical expression of S100/Mammaglobin/SOX10/DOG1 in distinction of SC from AciCC histologically. An electronic search of databases was carried out using MEDLINE by PubMed, Google scholar, Scopus and Web of science. Articles inclusive of SC and AciCC were assessed with S100/Mammaglobin/SOX10/DOG1 immunohistochemistry and their predominant expression pattern, predictive values, sensitivity and specificity were gathered. Fourteen eligible articles were analysed, which revealed predominant immunostaining pattern of S100 + /Mammaglobin + /SOX10 + /DOG1- by nearly all ETV6::NTRK3 fusion prevalent SCs alongside with other gene fusions like RET, MET and MAML3 with 98.4% sensitivity as well as 86.1% specificity. The evidence supports that S100/Mammaglobin/SOX10/DOG1 combined immunostaining can serve as a reliable diagnostic method to differentiate secretory from acinic cell carcinoma.

Prognosis of primary breast salivary gland-type carcinoma: a propensity score-matching analysis with invasive carcinoma of no special type based on the SEER database for years 2010-2020.

BACKGROUND: Primary breast salivary gland-type carcinoma has weak evidence to support its management due to its rare occurrence and limited data regarding its clinicopathological features and prognosis. Therefore, this study aimed to assess clinicopathological features and prognosis for this type of carcinoma diagnosed over the past decade and compared those to the common breast invasive carcinoma of no special type (NST). METHODS: This study used the Surveillance, Epidemiology, and End Results (SEER) database to extract data regarding primary breast salivary gland-type carcinoma. Using a propensity score-matching approach, the prognosis was compared with invasive carcinoma, NST. RESULTS: This study included 488 cases of salivary gland-type carcinoma and 375,660 cases of invasive carcinoma, NST, giving an occurrence ratio of 1 to 770. Adenoid cystic carcinoma (81%) formed the majority of salivary gland-type carcinoma, followed by secretory carcinoma (13%). For salivary gland-type carcinoma, acinic cell carcinoma histological type, tumor grade 3, HER2-overexpressed status, and higher AJCC stage groups were significant worse prognostic factors for breast cancer-specific survival in univariate analyses (p < 0.05). Nonetheless, tumor grade 3 and higher AJCC stage groups remained as significant independent prognostic factors in multivariate analysis (p < 0.05). The apparent better breast cancer-specific survival of salivary gland-type carcinoma as compared to that of invasive carcinoma, NST, was diminished following adjustment for differences in baseline clinicopathological features and treatment-related variables. CONCLUSIONS: This study suggests that when managing primary breast salivary gland-type carcinoma, greater emphasis should be given to the tumor grade and AJCC stage group in addition to acinic cell carcinoma histological type and HER2 overexpression. Conventional prognostic factors are important as salivary gland-type carcinoma had similar prognosis as invasive carcinoma, NST, following adjustment for confounding variables.

Multimodal ultrasonic manifestations of secretory carcinoma of the breast.

 Secretory carcinoma of the breast (SCB) is a rare and specific type of breast cancer. Owing to its rarity, the number of SCB reports available is limited, with most of them focusing on clinical and pathological characteristics but no reports on its multimodal ultrasound (US) features. Thus, we present a rare case of SCB, retrospectively analyzing manifestations of US and contrast-enhanced US, as well as its pathological basis, aiming to enhance the understanding of US image features of SCB and provide more valuable information for clinical diagnosis. Moreover, the treatment strategy adopted for this patient may serve as a template for future management of SCB.

Clinicopathological analysis of 18 cases of secretory carcinoma of the salivary glands.

Background/purpose: Secretory carcinoma (SC) is a rare salivary gland tumor that featured by ETV6::NTRK3 gene fusion, and was included in the WHO Classification of Head and Neck Tumors since 2017. Nevertheless, the description of SCs by WHO is still vague. This study examined 18 SC cases by using both histomorphology and molecular pathology for diagnostic determination, especially immunohistochemical features of SCs. Materials and methods: Based on WHO characteristics, 18 patients with SC admitted between 2001 and 2022 were included in this study. Main histomorphological patterns, FISH analyses of the ETV6::NTRK3 gene fusion, and immunohistochemical analyses of S100, mammaglobin, DOG1, ADFP, CA6 and Ki-67 were performed. Results: Among the 18 SC patients, the median age of onset was 39.22 years. Grossly, the average tumor size in 2.96 cm with various texture from soft to tough. The majority patients were positive for S100, mammaglobin, and negative for DOG1, except for one patient negative for S100 (Case 18). All patients were positive for ADFP, and the majority patients were negative for CA6, except for Case 9. Two cases were found recurrence, and the tumor were found both in parotid gland with local invasion. Conclusion: Combined with the results of previous studies, we proposed that the combination of all five markers, S100, mammaglobin, DOG1, ADFP and CA6, could contribute more to differential diagnosis of SCs with other salivary carcinomas, especially with AciCC. The prognosis of SCs is optimistic in most cases, but larger patient cohort and long-term follow-up are still needed.