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The American Journal of Dermatopathology Jun 2024Microsecretory adenocarcinoma (MSA) was first described in 2019 as a low-grade salivary gland neoplasm of intraoral origin with distinct histopathologic features and a...
Microsecretory adenocarcinoma (MSA) was first described in 2019 as a low-grade salivary gland neoplasm of intraoral origin with distinct histopathologic features and a characteristic MEF2C::SS18 fusion. Recently, skin was also identified as a primary site for MSA in a report by Bishop et al. Due to its rarity and resemblance to other adnexal tumors, MSA is a challenging diagnosis. Herein, we present a case of cutaneous MSA that was unique for the presence of a significant microcystic component and marked adnexal hyperplasia, which mimicked myxoid microcystic adnexal carcinoma (MAC). A 58-year-old presented with a 1 year history of an enlarging eyelid nodule. Histopathologic analysis revealed dermal tumor composed of small tubules containing inspissated bluish mucinous material. Accompanying marked adnexal hyperplasia and many microcysts were also present. Tumor cells expressed S100 protein, which is distinct from MAC, while p63 immunohistochemistry showed marked loss of myoepithelial labeling, as is common in primary adenocarcinomas. Next generation gene sequencing detected the characteristic MSA fusion protein MEF2c::SS18. We report a novel presentation of MSA that simulated MAC because of the presence of associated microcystic change. The presence of S100 immunopositivity and the identification of MEF2C::SS18 fusion confirmed the diagnosis of cutaneous MSA.
PubMed: 38941552
DOI: 10.1097/DAD.0000000000002788 -
Head and Neck Pathology Jun 2024Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated...
BACKGROUND
Intraductal carcinoma (IDC) of the salivary glands is a confounding entity, our understanding of which continues to evolve. At least four forms have been elucidated based on histomorphology, immunophenotype, and molecular profile: (1) intercalated duct-like, S100/SOX10+ with frequent NCOA4::RET fusions; (2) oncocytic, S100/SOX10+ with TRIM33::RET, NCOA4::RET, and BRAF V600E; (3) apocrine, AR+ with PI3 kinase pathway mutations; and (4) mixed/hybrid intercalated duct-like/apocrine, with S100/SOX10+ and AR+ areas and frequent TRIM27::RET. The revelation that myoepithelial cells harbor the same fusion as luminal cells suggested that fusion-positive cases are not in situ carcinomas as previously believed. To this point, purely apocrine IDC with entirely intraductal growth has not been found to harbor fusions, but very few cases have been tested.
METHODS
IDCs with pure apocrine morphology, entirely intraductal growth, and no precursor lesion (pleomorphic adenoma or sclerosing polycystic adenoma) were retrieved from the authors' archives. Several immunostains (S100, SOX10, GCDFP-15, AR, p40/SMA) and targeted next generation sequencing (NGS) panel including 1425 cancer-related genes were performed.
RESULTS
Seven entirely IDC with pure apocrine type were collected. The cases arose in the parotid glands (mean, 1.9 cm) of 5 men and 2 women ranging from 51 to 84 years (mean, 69.7 years). Histologically, tumors consisted of rounded to angulated ductal cysts lined by epithelial cells with abundant finely granular eosinophilic cytoplasm and large nuclei with prominent nucleoli. Pleomorphism was mild to moderate, the mitotic rate was low, and necrosis was absent. Conventionally invasive foci or areas of intercalated duct-like morphology were not identified. In all cases, luminal cells were diffusely positive for AR and GCDFP-15 while negative for S100/SOX10, and the ducts were completely surrounded by myoepithelial cells highlighted by p40 and SMA. Molecular analysis was successful in 6 cases. Three harbored fusions: one with NCOA4::RET, another with STRN::ALK and one with both CDKN2A::CNTRL and TANC1::YY1AP1. The three fusion-negative cases all harbored HRAS mutations; additional mutations (PIK3CA, SPEN, ATM) were found in 2 of 3 cases. All patients were treated by surgery alone. Six of them are currently free of disease (follow up 12-190 months), but the case harboring NCOA4::RET developed lymph nodes metastasis in the form of a fusion-positive invasive salivary duct carcinoma.
CONCLUSIONS
Purely apocrine IDC is a heterogeneous disease. A subset seems to be genetically similar to salivary duct carcinoma and may indeed represent carcinoma in situ. The other group harbors fusions, similar to other forms of IDC. Moreover, the occurrence of lymph node metastasis discredits the idea that any fusion-positive IDC with a complete myoepithelial cell layer has no metastatic potential. With the wide use of RET-and ALK-based targeted therapies, our findings further underscore the importance of fusion analysis for IDC.
Topics: Humans; Male; Middle Aged; Aged; Female; Salivary Gland Neoplasms; Aged, 80 and over; Carcinoma, Intraductal, Noninfiltrating; Biomarkers, Tumor; Adult; Carcinoma, Ductal
PubMed: 38935197
DOI: 10.1007/s12105-024-01653-2 -
Diagnostic Cytopathology Jun 2024Myoepithelial carcinoma (MC) arises from the myoepithelial cells. It is a rare tumor with a predilection for salivary glands. MC in soft tissue is uncommon. Soft tissue...
Myoepithelial carcinoma (MC) arises from the myoepithelial cells. It is a rare tumor with a predilection for salivary glands. MC in soft tissue is uncommon. Soft tissue MC exhibits dual epithelial and smooth muscle phenotype. The extremities and limb girdles are commonly affected. We present cytological findings of retroperitoneal MC with an accurate diagnosis being rendered with the aid of immunocytochemistry on the cell block and demonstration of EWSR1 rearrangements by fluorescence in situ hybridization on cytology smear. The smears were cellular, showing loose clusters and sheets of tumor cells embedded in dense eosinophilic to myxoid matrix material. The cells were oval to polygonal, with focal areas showing moderate nuclear pleomorphism, vesicular to coarse chromatin, and vacuolated cytoplasm with clearing. On immunocytochemistry, tumor cells were positive for epithelial membrane antigen, pan-cytokeratin, calponin, smooth muscle actin, and S-100. A literature review shows only a handful of cases of soft tissue MC. The current report emphasizes the need for cytomorphological awareness with the employment of ancillary testing for accurately diagnosing this rare tumor at an uncommon location. We also discuss the diagnostic challenges and troubleshooting.
PubMed: 38923864
DOI: 10.1002/dc.25375 -
Diagnostic Cytopathology Jun 2024Mammary analogue secretory carcinoma (MASC) is a rare salivary gland tumor which shares its histologic, immunohistochemical, and genetic features with the secretory...
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.
PubMed: 38923370
DOI: 10.1002/dc.25377 -
Histopathology Jun 2024Low-grade non-intestinal-type sinonasal adenocarcinoma (LGSNAC) is a rare heterogeneous and poorly characterised group of tumours, distinct from intestinal- and...
AIMS
Low-grade non-intestinal-type sinonasal adenocarcinoma (LGSNAC) is a rare heterogeneous and poorly characterised group of tumours, distinct from intestinal- and salivary-type neoplasms. Therefore, further characterisation is needed for clearer biological understanding and classification.
METHODS AND RESULTS
Clinical, histological and molecular characterisation of four cases of biphasic, low-grade adenocarcinomas of the sinonasal tract was performed. All patients were male, aged between 48 and 78 years, who presented with polypoid masses in the nasal cavity. Microscopically, virtually all tumours were dominated by tubulo-glandular biphasic patterns, microcystic, focal (micro)papillary, oncocytic or basaloid features. Immunohistochemical staining confirmed biphasic differentiation with an outer layer of myoepithelial cells. Molecular profiling revealed HRAS (p.G13R, p.Q61R) mutations, and concomitant AKT1 (p.E17K, p.Q79R) mutations in two cases. Two cases showed potential in-situ/precursor lesions adjacent to the tumour. Follow-up periods ranged from 1 to 30 months, with one case relapsing locally after 12 and > 20 years.
CONCLUSION
This study further corroborates a distinct biphasic low-grade neoplasm of the sinonasal tract with seromucinous differentiation. Although morphological and molecular features overlap with salivary gland epithelial-myoepithelial carcinoma, several arguments favour categorising these tumours within the spectrum of LGSNAC.
PubMed: 38923026
DOI: 10.1111/his.15251 -
Frontiers in Oncology 2024Breast cancer is the second most diagnosed cancer, as well as the primary cause of cancer death in women worldwide. Of the different breast cancer subtypes,...
INTRODUCTION
Breast cancer is the second most diagnosed cancer, as well as the primary cause of cancer death in women worldwide. Of the different breast cancer subtypes, triple-negative breast cancer (TNBC) is particularly aggressive and is associated with poor prognosis. Black women are two to three times more likely to be diagnosed with TNBCs than white women. Recent experimental evidence suggests that basal-like TNBCs may derive from luminal cells which acquire basal characteristics through phenotypic plasticity, a newly recognized hallmark of cancer. Whether chemical exposures can promote phenotypic plasticity in breast cells is poorly understood.
METHODS
To investigate further, we developed a high-content immunocytochemistry assay using normal human breast cells to test whether chemical exposures can impact luminal/basal plasticity by unbiased quantification of keratin 14 (KRT14), a basal-myoepithelial marker; keratin 8 (KRT8), a luminal-epithelial marker; and Hoechst 33342, a DNA marker. Six cell lines established from healthy tissue from donors to the Susan G. Komen Normal Tissue Bank were exposed for 48 hours to three different concentrations (0.1μM, 1μM, and 10μM) of eight ubiquitous chemicals (arsenic, BPA, BPS, cadmium, copper, DDE, lead, and PFNA), with documented exposure disparities in US Black women, in triplicate. Automated fluorescence image quantification was performed using Cell Profiler software, and a random-forest classifier was trained to classify individual cells as KRT8 positive, KRT14 positive, or hybrid (both KRT8 and KRT14 positive) using Cell Profiler Analyst.
RESULTS AND DISCUSSION
Results demonstrated significant concentration-dependent increases in hybrid populations in response to BPA, BPS, DDE, and PFNA. The increase in hybrid populations expressing both KRT14 and KRT8 is indicative of a phenotypically plastic progenitor-like population in line with known theories of carcinogenesis. Furthermore, BPA, BPS, DDE, and copper produced significant increases in cell proliferation, which could be indicative of a more malignant phenotype. These results further elucidate the relationship between chemical exposure and breast phenotypic plasticity and highlight potential environmental factors that may impact TNBC risk.
PubMed: 38915368
DOI: 10.3389/fonc.2024.1411295 -
World Journal of Clinical Cases Jun 2024Salivary gland tumors are relatively rare. Most minor salivary gland tumors are malignant with benign tumors accounting for 18% of the tumors. Pleomorphic adenoma (PA)...
BACKGROUND
Salivary gland tumors are relatively rare. Most minor salivary gland tumors are malignant with benign tumors accounting for 18% of the tumors. Pleomorphic adenoma (PA) is the most common salivary gland tumor. Lip PA is uncommon with 9.8% occurring in the upper lip. We are adding on the knowledge of the rare upper lip PA (benign mixed tumor).
CASE SUMMARY
We report an upper lip PA (benign mixed tumor) in a 28-year-old man. His complaint was a painless swelling on the upper lip. A painless, non-tender, well-circumscribed, slightly mobile, sessile, nodular, and rubbery (in consistency) tumor measuring 5.0 cm x 2.0 cm was noted on the left side of his upper lip. The overlying skin was not fixed and of normal color. There was no ulceration, and palpation did not elicit pain or bleeding. There was no history of trauma. Blunt dissection was used to completely excise the nodular, whitish, and encapsulated tumor. Microscopy showed a well-circumscribed and partly encapsulated biphasic lesion, with large lobules of myxo-chondroid stroma and intervening cellular nodules of basaloid cells, well-formed tubules containing eosinic secretion, and nests of myoepithelial cells. A diagnosis of PA (benign mixed tumor) was confirmed.
CONCLUSION
Blunt dissection is indicated to preserve the cosmesis and function of the upper lip.
PubMed: 38898865
DOI: 10.12998/wjcc.v12.i17.3138 -
Human Pathology Jun 2024Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have...
Ancillary immunohistochemical and molecular testing in the classification of cutaneous sweat gland/duct neoplasms: A validation study with emphasis on histomorphologic correlation and pathological diagnosis.
Sweat gland neoplasms represent a challenging area of dermatopathology, as they are relatively uncommon and often histopathologically complex. Recent studies have uncovered distinct immunohistochemical and molecular profiles in several sweat gland neoplasms, including digital papillary adenocarcinoma (DPA), papillary eccrine adenoma/tubular apocrine adenoma (PEA/TAA), poroid family tumors (PFT)/porocarcinoma, and clear cell hidradenoma (CCH)/clear cell hidradenocarcinoma (CCHCa). To further evaluate the diagnostic utility of ancillary studies in various sweat gland neoplasms, we performed an independent validation study in a cohort of patients with acral and non-acral tumors (9 DPA, 8 PEA/TAA, 13 PFT, 5 porocarcinoma, 23 CCH, 7 CCHCa, 6 sweat gland carcinoma not otherwise specified). p63 immunohistochemistry (IHC) demonstrated a myoepithelial pattern in 8/8 DPA and 4 of 4 tested PEA/TAA cases, and showed a ductal pattern in all tested PFT/porocarcinoma and CCH/CCHCa cases (42/42). All PEA/TAA (8/8) cases were positive for BRAF V600E IHC. 5 of 12 tested PFT and 5/5 porocarcinoma cases showed either positive staining with NUT IHC or harbored YAP1::NUTM1 fusion gene by RNA sequencing. MAML2 fluorescence in situ hybridization (FISH) was positive in all CCH and CCHCa cases (23/23 and 7/7, respectively). Our results further support the usefulness of appropriate ancillary studies in precise classification of sweat gland tumors, which may be routinely applied in diagnostic pathology practice when morphologic evaluation is in doubt.
PubMed: 38876201
DOI: 10.1016/j.humpath.2024.06.006 -
Nature Communications Jun 2024Spatially resolved transcriptomics (SRT) has enabled precise dissection of tumor-microenvironment (TME) by analyzing its intracellular molecular networks and...
Spatially resolved transcriptomics (SRT) has enabled precise dissection of tumor-microenvironment (TME) by analyzing its intracellular molecular networks and intercellular cell-cell communication (CCC). However, lacking computational exploration of complicated relations between cells, genes, and histological regions, severely limits the ability to interpret the complex structure of TME. Here, we introduce stKeep, a heterogeneous graph (HG) learning method that integrates multimodality and gene-gene interactions, in unraveling TME from SRT data. stKeep leverages HG to learn both cell-modules and gene-modules by incorporating features of diverse nodes including genes, cells, and histological regions, allows for identifying finer cell-states within TME and cell-state-specific gene-gene relations, respectively. Furthermore, stKeep employs HG to infer CCC for each cell, while ensuring that learned CCC patterns are comparable across different cell-states through contrastive learning. In various cancer samples, stKeep outperforms other tools in dissecting TME such as detecting bi-potent basal populations, neoplastic myoepithelial cells, and metastatic cells distributed within the tumor or leading-edge regions. Notably, stKeep identifies key transcription factors, ligands, and receptors relevant to disease progression, which are further validated by the functional and survival analysis of independent clinical data, thereby highlighting its clinical prognostic and immunotherapy applications.
Topics: Tumor Microenvironment; Humans; Transcriptome; Neoplasms; Gene Expression Regulation, Neoplastic; Gene Expression Profiling; Cell Communication; Computational Biology; Gene Regulatory Networks; Machine Learning
PubMed: 38871687
DOI: 10.1038/s41467-024-49171-7