secretory carcinoma
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2022 ◽  
Vol 20 (6) ◽  
pp. 120-133
Author(s):  
A. A. Kechin ◽  
A. I. Andriyanova ◽  
M. L. Filipenko

Background. The first-generation trk inhibitors, larotrectinib and entrectinib, were approved by the u.s. Food and drug administration (Fda) for the treatment of advanced solid tumors harboring NTRK gene fusions in November 2018 and in august 2019, respectively. The purpose of the study was to present upto-date data on the structure and functions of ntrk genes, the frequency of occurrence of rearrangements with their participation, the consequences of their occurrence at the cellular level, methods of detecting such rearrangements, as well as targeted drugs used in the presence of chimeric NTRK genes. Material and methods. A systemic literature search was conducted in pubmed ncbi, Web of science, scopus databases. Results. The products of NTRK genes are receptors for neurotrophins, and their high expression is normally observed only in a narrow range of tissue types. Intrachromosomal or interchromosomal rearrangements lead to a significant increase in the level of expression of the chimeric gene regulated by the strong promoter of the partner gene. The high transcriptional activity of such a gene, along with the constant activation of the kinase activity of the protein product, leads to the activation of metabolic pathways responsible for cell escape from apoptosis and disruption of the regulation of the cell cycle. The occurrence of chimeric NTRK genes varies between different types of tumors, with the highest (up to 90 %) in rare cancers (secretory carcinoma of the breast, secretory carcinoma of the salivary glands, congenital mesoblastic nephroma, children’s fibrosarcoma). Larotrectinib and entrectinib are highly effective targeted drugs in suppressing the growth of a tumor carrying NTRK rearrangements, regardless of the type of tumor. In this regard, the introduction of new high-precision methods for the detection of chimeric NTRK genes, as well as the study of the mechanisms of the development of resistance with the assumption of ways to overcome it, seems relevant. Conclusion. Rearrangements of NTRK genes are quite common in various types of oncology and are an effective target for modern targeted drugs.


2022 ◽  
Vol 15 (1) ◽  
Author(s):  
Kensuke Suzuki ◽  
Hiroshi Harada ◽  
Masayuki Takeda ◽  
Chisato Ohe ◽  
Yoshiko Uemura ◽  
...  

Abstract Background Secretory carcinoma (SC) of the salivary gland is a recently described malignant tumor harboring characteristic ETV6-NTRK3 gene fusion. SC generally has a favorable clinical course, and is currently regarded as a low-grade carcinoma. However, a small subset of SCs demonstrates aggressive clinical features with histologically high-grade transformed morphology, the molecular pathogenesis of which has not yet been elucidated. In this study, we performed a clinicopathological and molecular genetic study of patients with SC of the head and neck displaying various clinical characteristics to investigate the differences of pathological and molecular genetics between low-grade and high-grade components of SC. Case presentation Three cases with SC of the head and neck, including a conventional low-grade SC and two high-grade transformed SCs are described. High-grade transformed SCs with histological features such as nuclear polymorphism, distinctive nucleoli and increased mitotic activity developed locoregional recurrence and distant metastasis. Immunohistochemical analysis revealed that low- and high-grade components showed different expression patterns for S-100 protein and mammaglobin, whereas all examined components were positive for p-STAT5. p53-positive cell population was markedly higher in one case with high-grade transformed SC. The proliferative activity of high-grade components was markedly increased, with the Ki-67 labeling index ranging up to 30–32%. A fluorescence in situ hybridization study with an ETV6 (12p13) break apart probe revealed split signals in the nuclei in all 3 cases. A targeted next-generation sequencing-based fusion assay demonstrated that all 6 clinical samples from the 3 patients showed the presence of the ETV6-NTRK3 fusion transcripts. One patient with high-grade transformed SC showed a dramatic clinical response to the pan-TRK inhibitor, entrectinib, for the treatment of locoregional recurrence and pulmonary metastasis. Conclusions High-grade transformed SC showed aggressive clinical and pathological features with increased Ki-67 labeling index. Molecular genetic study of gene rearrangement appears to be beneficial treatment as the presence of ETV6-NTRK3 translocation may represent a therapeutic target in SC, particularly the high-grade transformed type.


2022 ◽  
Vol 2 (1) ◽  
pp. 87-92
Author(s):  
RITA STEFANUCCI ◽  
DOMIZIANA SANTUCCI ◽  
SILVIA MARIA ROSSI ◽  
MATTEO SAMMARRA ◽  
ELIODORO FAIELLA ◽  
...  

Background: Secretory and medullary carcinomas of the breast are rare subtypes of infiltrating ductal carcinoma. The different histological behavior of medullary and secretory carcinomas is correlated with different imaging features on mammography, ultrasound, and magnetic resonance imaging. Case Report: We report the case of a Caucasian woman in which both subtypes of tumors were diagnosed in an 8-year time interval and evaluate, in antithesis, histopathological and imaging aspects of medullary and secretory carcinoma. Conclusion: To our knowledge, this is the first case reported in literature of secretory carcinoma with a complete imaging tumor evaluation in a patient with a previous contralateral medullary cancer.


Author(s):  
Daliah Abdulhafeez ◽  
◽  
Abdullah Ghafouri ◽  

Mammary analogue secretory carcinoma is a rare salivary gland tumor that has a wide range of clinical presentation ranging from indolent, local and slowly growing tumors to a very aggressive, infiltrative and widely metastasizing forms. We report a case of an unfortunate patient whose tumor had a very quick ominous disease course with aggressive clinical and histological presentation. This case is the first case, to our knowledge, to be reported in the literature from Saudi Arabia of MASC with features of high grade transformation


Medicine ◽  
2021 ◽  
Vol 100 (51) ◽  
pp. e28390
Author(s):  
Masaru Ogawa ◽  
Satoshi Yokoo ◽  
Takahiro Yamaguchi ◽  
Keisuke Suzuki ◽  
Mai Seki-Soda ◽  
...  

Diagnostics ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2284
Author(s):  
Yuria Egusa ◽  
Midori Filiz Nishimura ◽  
Satoko Baba ◽  
Kengo Takeuchi ◽  
Takuma Makino ◽  
...  

Secretory carcinoma is a salivary gland neoplasm first described as a mammary analogue secretory carcinoma by Skalova et al. in 2010 and redesignated as a secretory carcinoma in the 2017 World Health Organization Classification of Head and Neck Tumors. Secretory carcinoma diagnosis is reliant on specific cytological and histological findings and the detection of an ETV6-NTRK3 fusion gene. Here, we examined the clinical and cytopathological features of four cases of secretory carcinoma occurring in three males and a female, aged between 39 and 74 years. All four tumors involved the parotid gland, and were found to have the ETV6-NTRK3 fusion gene. Fine-needle aspiration-based cytology smears of all tumors displayed papillary and/or dendritic pattern clusters, some of which were associated with blood vessels. The neoplastic cells displayed enlarged nuclei with fine chromatin and small, distinct, single nucleoli. Furthermore, several neoplastic cells with a characteristic vacuolated cytoplasm were identified in each specimen. Giemsa staining revealed cytoplasmic vacuolation, intracytoplasmic metachromatic secretions and/or various sized metachromatic granules, and a background of metachromatic mucin in all four specimens. Given this, we conclude that these cytological findings, especially those of the Giemsa staining, might be helpful in the diagnosis of secretory carcinoma.


2021 ◽  
Vol 7 (4) ◽  
pp. 100236
Author(s):  
Yousef Hammad ◽  
Ali Edrisi ◽  
Timothy W. Neal ◽  
Yisheng Fang ◽  
Thomas Schlieve

2021 ◽  
Vol 8 (12) ◽  
pp. 3731
Author(s):  
Iram T. Pasha ◽  
Akhila K. ◽  
Ravikumar V. ◽  
Sandeep Kumar

A recent described entity, mammary analogue secretary carcinoma (MASC) in 2010 by Skalova et al whose morphological and immunohistochemical features are similar in secretory carcinoma of the breast and salivary gland. This is a low-grade carcinoma which presents as a firm, slow-growing, circumscribed lesion with male preponderance. We present a case report of MASC.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jingjing Sun ◽  
Sirui Liu ◽  
Kun Fu ◽  
Ning Gao ◽  
Rui Li ◽  
...  

AbstractThis retrospective study investigated the clinicopathological characteristics of secretory carcinoma of salivary glands (SCSG) in 23 patients with histopathologically confirmed SCSG between January 2010 and December 2020. In total, 13 males and 10 females (ratio, 1.3:1) aged 10 − 69 years (median, 45 years) were enrolled in this study; the average disease duration was 2.44 years (0.25–20 years). Twenty-one patients (91.3%) had SCSG in the parotid gland, and two (8.7%) in the submandibular gland. All patients had single nodules of diameters 0.8–4.8 cm (average 2.6 cm); five with lymph node metastases, and two with distant metastases. Immunohistochemically, tumors stained positive for S-100, mammaglobin, CK7, GATA3 and pan-Trk, and negative for DOG1, P63, and calponin, with Ki-67 positivity from 1 to 50%. ETV6 gene rearrangement was confirmed in 15 patients. All patients underwent oncological resection, four had radioactive particles implanted postoperatively, one received chemotherapy, and seven underwent chemoradiotherapy. Six patients had regional recurrences, two distant metastases, and one died before the last follow-up. SCSGs are typically indolent, with a low locoregional recurrence rate and excellent survival. Prognosis is correlated to clinical stage, pathological grade, and surgical procedures.


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