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Cancers Jan 2022Cutaneous sweat gland tumors are a subset of adnexal neoplasms that derive or differentiate into the sweat apparatus. Their great diversity, rarity, and complex... (Review)
Review
Cutaneous sweat gland tumors are a subset of adnexal neoplasms that derive or differentiate into the sweat apparatus. Their great diversity, rarity, and complex terminology make their pathological diagnosis challenging. Recent findings have revealed a wide spectrum of oncogenic drivers, several of which are of diagnostic interest for pathologists. Most of these molecular alterations are represented by gene fusions, which are shared with other homologous neoplasms occurring in organs containing exocrine glands, such as salivary and breast glands, which show similarities to the sweat apparatus. This review aims to provide a synthesis of the most recent immunohistochemical and molecular markers used for the diagnosis of sweat gland tumors and to highlight their relationship with similar tumors in other organs. It will cover adenoid cystic carcinoma (, and fusion), cutaneous mixed tumor ( fusion), cylindroma and spiradenoma and their carcinomas thereof (NF-κB activation through inactivation or hotspot mutation), hidradenoma and hidradenocarcinoma ( fusion), myoepithelioma ( and fusion), poroma and porocarcinoma (, and fusion), secretory carcinoma (, fusion), tubular adenoma and syringo-cystadenoma papilliferum ( and activating mutations). Sweat gland tumors for which there are no known molecular abnormalities will also be briefly discussed, as well as potential future developments.
PubMed: 35158743
DOI: 10.3390/cancers14030476 -
Surgical Pathology Clinics Mar 2021Myoepithelial carcinoma (MECA) may overlap histologically with other salivary gland neoplasms, especially pleomorphic adenoma. MECA is characterized by cellular, uniform... (Review)
Review
Myoepithelial carcinoma (MECA) may overlap histologically with other salivary gland neoplasms, especially pleomorphic adenoma. MECA is characterized by cellular, uniform growth of myoepithelial cells and multinodular expansile invasive pattern with zonal cellular distribution. It may arise de novo or in association with pleomorphic adenoma (myoepithelial carcinoma ex pleomorphic adenoma). By immunohistochemistry, MECA is positive for cytokeratins and at least one of the myoepithelial markers, including S100. PLAG1 fusion is the most common genetic alteration. Carcinoma ex pleomorphic adenoma and necrosis correlate with worse clinical outcome in MECA, and necrosis can be used to stratify MECA as high grade.
Topics: Adenoma, Pleomorphic; Diagnosis, Differential; Epithelial Cells; Humans; Immunohistochemistry; Myoepithelioma; Necrosis; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Prognosis; Salivary Gland Neoplasms
PubMed: 33526224
DOI: 10.1016/j.path.2020.09.008 -
The Journal of International Advanced... Aug 2020Parachordoma is a rare soft tissue mixed tumor, associated with soft tissue myoepithelioma. It is typically growing slowly and considered less aggressive than other...
Parachordoma is a rare soft tissue mixed tumor, associated with soft tissue myoepithelioma. It is typically growing slowly and considered less aggressive than other similar soft tissue tumors. However, it does recur sporadically, and on rare occasions, it has demonstrated the ability to metastasize. Although imaging is important, definitive diagnosis is achieved by histology, and it is typically treated by a wide local excision. We present the first reported case of a skull base parachordoma in a 15-year-old boy, managed with a wide local excision and with no signs of recurrence or metastases after 24 months of follow-up.
Topics: Adolescent; Chordoma; Diagnosis, Differential; Humans; Male; Myoepithelioma; Skull Base; Skull Base Neoplasms; Soft Tissue Neoplasms; Temporal Bone
PubMed: 32147599
DOI: 10.5152/iao.2020.7203 -
Frontiers in Oncology 2022Malignant myoepithelioma of the head and neck (HNMM) is a rare malignancy, and its characteristics and survival rates have not been well-defined. This study aimed to...
Malignant myoepithelioma of the head and neck (HNMM) is a rare malignancy, and its characteristics and survival rates have not been well-defined. This study aimed to define the epidemiology of HNMM and identify the prognostic factors associated with the disease. Data on all patients diagnosed with HNMM between 1991 and 2016 were gathered from the Surveillance Epidemiology and End Results (SEER) database. The demographics, clinicopathological characteristics, treatment, and prognoses of the patients were described. Cox regression analysis was used to identify the prognostic factors, and the prognostic nomograms for overall survival (OS) and disease-specific survival (DSS) were constructed. A total of 333 cases of HNMM were identified. The average age at diagnosis was 60.6 years, and 50.1% of the patients were men. After diagnosis, 46.2% of patients underwent surgery alone, 43.5% of patients underwent surgery and radiotherapy, and 3.6% of patients received only radiotherapy. Survival analysis showed that the 5-year OS and DSS for all HNMM patients were 69.7 and 82.1%, respectively. In the multivariate analysis model, the undifferentiated pathological grade (P <0.05) and M1 in the M category (P <0.01) were independent prognostic factors for poor OS and DSS, whereas the use of surgical resection was an independent favorable prognostic factor for both OS and DSS (P <0.05). The prognostic nomograms for OS and DSS prediction were constructed; the C-index values for OS and DSS prediction were 0.78 (95% CI 0.70-0.86) and 0.79 (95% CI 0.67-0.90), respectively. In conclusion, this SEER data-based study demonstrated that HNMM patients often had a favorable prognosis, and distant metastasis, pathological grade, and the use of surgery contributed to their survival. Furthermore, we developed a prognostic nomogram to predict OS and DSS for HNMM patients to aid physicians in the clinical management of this rare disease.
PubMed: 35847870
DOI: 10.3389/fonc.2022.754967 -
International Journal of Oral Science Sep 2023Pleomorphic adenoma (PA) is the most common benign tumour in the salivary gland and has high morphological complexity. However, the origin and intratumoral heterogeneity...
Pleomorphic adenoma (PA) is the most common benign tumour in the salivary gland and has high morphological complexity. However, the origin and intratumoral heterogeneity of PA are largely unknown. Here, we constructed a comprehensive atlas of PA at single-cell resolution and showed that PA exhibited five tumour subpopulations, three recapitulating the epithelial states of the normal parotid gland, and two PA-specific epithelial cell (PASE) populations unique to tumours. Then, six subgroups of PASE cells were identified, which varied in epithelium, bone, immune, metabolism, stemness and cell cycle signatures. Moreover, we revealed that CD36 myoepithelial cells were the tumour-initiating cells (TICs) in PA, and were dominated by the PI3K-AKT pathway. Targeting the PI3K-AKT pathway significantly inhibited CD36 myoepithelial cell-derived tumour spheres and the growth of PA organoids. Our results provide new insights into the diversity and origin of PA, offering an important clinical implication for targeting the PI3K-AKT signalling pathway in PA treatment.
Topics: Humans; Adenoma, Pleomorphic; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Transcriptome; Myoepithelioma
PubMed: 37679344
DOI: 10.1038/s41368-023-00243-2 -
The genetic landscape of SMARCB1 alterations in SMARCB1-deficient spectrum of mesenchymal neoplasms.Modern Pathology : An Official Journal... Dec 2022SMARCB1 biallelic inactivation resulting in SMARCB1/INI1 deficiency drives a wide range of malignancies, including many mesenchymal tumors. However, the specific types...
SMARCB1 biallelic inactivation resulting in SMARCB1/INI1 deficiency drives a wide range of malignancies, including many mesenchymal tumors. However, the specific types of SMARCB1 alterations and spectrum of cooperating mutations among various types of sarcomas has not been well investigated. We profiled SMARCB1 genetic alterations by targeted DNA sequencing and fluorescence in situ hybridization (FISH) in a large cohort of 118 soft tissue and bone tumors, including SMARCB1-deficient sarcomas (78, 66%): epithelioid sarcomas, epithelioid peripheral nerve sheath tumors, poorly differentiated chordomas, malignant rhabdoid tumors, and soft tissue myoepithelial tumors, as well as non-SMARCB1-deficient sarcomas (40, 34%) with various SMARCB1 genetic alterations (mutations, copy number alterations). SMARCB1 loss by immunohistochemistry was present in 94% SMARCB1 pathogenic cases. By combined sequencing and FISH assays, 80% of SMARCB1-deficient tumors harbored homozygous (biallelic) SMARCB1 loss, while 14% demonstrated heterozygous SMARCB1 loss-of-function (LOF) alterations, and 6% showed no demonstrable SMARCB1 alterations. FISH and sequencing were concordant in the ability to detect SMARCB1 loss in 48% of cases. Epithelioid sarcomas most commonly (75%) harbored homozygous deletions, while a subset showed focal intragenic deletions or LOF mutations (nonsense, frameshift). In contrast, most soft tissue myoepithelial tumors (83%) harbored SMARCB1 nonsense point mutations without copy number losses. Additionally, clinically significant, recurrent co-occurring genetic events were rare regardless of histotype. By sequencing, extended 22q copy number loss in genes flanking the SMARCB1 locus (22q11.23) occurred in one-third of epithelioid sarcomas and the majority of poorly differentiated chordomas. Poorly differentiated chordomas and soft tissue myoepithelial tumors showed significantly worse overall and disease-free survival compared to epithelioid sarcomas. Overall, SMARCB1 LOF alterations predominate and account for SMARCB1 protein loss in most cases: majority being biallelic but a subset were heterozygous. In contrast, SMARCB1 alterations of uncertain significance can be seen in diverse sarcomas types and does not indicate a SMARCB1-deficient entity.
Topics: Humans; SMARCB1 Protein; In Situ Hybridization, Fluorescence; Myoepithelioma; Chordoma; DNA-Binding Proteins; Transcription Factors; Chromosomal Proteins, Non-Histone; Rhabdoid Tumor; Neoplasms, Connective and Soft Tissue; Sarcoma; Soft Tissue Neoplasms
PubMed: 36088476
DOI: 10.1038/s41379-022-01148-x -
Frontiers in Oncology 2022Among sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases...
BACKGROUND
Among sarcomas, which are rare cancers with an incidence of <6 per 100.000/year cases, ultra-rare sarcomas have an incidence of approximately ≤1/1,000,000/year cases and altogether account for ~20% of all soft tissue sarcomas (STS) and bone sarcomas. The Italian Sarcoma Group has recently performed a non-interventional, retrospective TrObs study with data from 512 anthracycline-pretreated patients with advanced multiple STS histologies and treated with trabectedin (Palmerini, 2021; ClinicalTrials.gov Identifier: NCT02793050).
METHODS
A analysis of case series to evaluate the efficacy and safety of trabectedin on patients with ultra-rare and other rare translocation-related sarcomas included in TrObs study was performed. Main outcomes comprised investigator-assessed overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety.
RESULTS
Thirty-six patients (18 women) with ultra-rare and other rare sarcoma and a median age of 53.0 years (range: 22-81) were included. Most patients had solitary fibrous tumor (SFT; n=11) followed by epithelioid sarcoma (n=5), malignant peripheral nerve sheath tumor (MPNST; n=4), extraskeletal myxoid chondrosarcoma (EMC; n=3), desmoplastic small round cell tumor (DSRCT; n=3), and alveolar soft part sarcoma (ASPS), rhabdomyosarcoma and clear cell sarcoma (n=2 each). Thirty-five patients had metastatic disease and 23 patients received trabectedin as a second-line treatment. Among 35 patients evaluable for response, two patients with SFT and ASPS had a partial response and one patient with DSRCT obtained a complete response, reaching an ORR of 8.6% (95% CI: 2.8-23.4%). Among patients with an ORR, 6-months PFS was 100% in patients with ASPS, 45.7% in patients with SFT and 33.3% in those with DSRCT. Two patients with epithelioid sarcoma and myoepithelioma had disease stabilization lasting >24 months. Nine patients had at least one grade 3/4 adverse event, mostly being bone marrow toxicity (n=6).
CONCLUSIONS
Trabectedin has some anti-tumor activity in some ultra-rare and other rare sarcomas, particularly translocation-related sarcomas, with the well-known manageable safety profile.
PubMed: 36568164
DOI: 10.3389/fonc.2022.1042479 -
Advances in Therapy Aug 2019A vast increase in knowledge of numerous aspects of malignant salivary gland tumours has emerged during the last decade and, for several reasons, this has not been the... (Review)
Review
INTRODUCTION
A vast increase in knowledge of numerous aspects of malignant salivary gland tumours has emerged during the last decade and, for several reasons, this has not been the case in benign epithelial salivary gland tumours. We have performed a literature review to investigate whether an accurate histological diagnosis of the 11 different types of benign epithelial salivary gland tumours is correlated to any differences in their clinical behaviour.
METHODS
A search was performed for histological classifications, recurrence rates and risks for malignant transformation, treatment modalities, and prognosis of these tumours. The search was performed primarily through PubMed, Google Scholar, and all versions of WHO classifications since 1972, as well as numerous textbooks on salivary gland tumours/head and neck/pathology/oncology. A large number of archival salivary tumours were also reviewed histologically.
RESULTS
Pleomorphic adenomas carry a considerable risk (5-15%) for malignant transformation but, albeit to a much lesser degree, so do basal cell adenomas and Warthin tumours, while the other eight types virtually never develop into malignancy. Pleomorphic adenoma has a rather high risk for recurrence while recurrence occurs only occasionally in sialadenoma papilliferum, oncocytoma, canalicular adenoma, myoepithelioma and the membranous type of basal cell adenoma. Papillomas, lymphadenoma, sebaceous adenoma, cystadenoma, basal cell adenoma (solid, trabecular and tubular subtypes) very rarely, if ever, recur.
CONCLUSIONS
A correct histopathological diagnosis of these tumours is necessary due to (1) preventing confusion with malignant salivary gland tumours; (2) only one (pleomorphic adenoma) has a considerable risk for malignant transformation, but all four histological types of basal cell adenoma can occasionally develop into malignancy, as does Warthin tumour; (3) sialadenoma papilliferum, oncocytoma, canalicular adenoma, myoepithelioma and Warthin tumour only occasionally recur; while (4) intraductal and inverted papilloma, lymphadenoma, sebaceous adenoma, cystadenoma, basal cell adenoma (apart from the membranous type) virtually never recur. No biomarker was found to be relevant for predicting recurrence or potential malignant development. Guidelines for appropriate treatment strategies are given.
Topics: Adenoma; Adenoma, Pleomorphic; Adult; Aged; Aged, 80 and over; Female; Humans; Male; Middle Aged; Salivary Glands
PubMed: 31209701
DOI: 10.1007/s12325-019-01007-3 -
Head and Neck Pathology Mar 2023Myoepithelial neoplasms of the salivary gland are benign or malignant neoplasms composed exclusively of neoplastic myoepithelial cells. These tumors, including the... (Review)
Review
BACKGROUND
Myoepithelial neoplasms of the salivary gland are benign or malignant neoplasms composed exclusively of neoplastic myoepithelial cells. These tumors, including the benign myoepithelioma and the malignant counterpart myoepithelial carcinoma, exhibit a wide range of cytomorphologic features and architectural patterns.
METHODS
Review.
RESULTS
Myoepithelial cells can be epithelial, plasmacytoid, clear cell, spindle cell, and/or oncocytic cell, arranging as trabeculae, solid sheets, nests, cords, and/or single cells. A stromal component is commonly but not universally present, Therefore, their differential diagnoses are quite broad, including salivary gland neoplasms especially those with a myoepithelial component, plasmacytoma, melanoma, and various mesenchymal tumors.
CONCLUSION
In this review, we summarize the characteristic histologic features, useful immunohistochemical panel, and common molecular alterations of myoepithelial tumors and their top differential diagnoses. A logical stepwise algorithmic approach and an immunohistochemical panel to include multiple myoepithelial markers are essential to establish the correct diagnosis.
Topics: Humans; Biomarkers, Tumor; Immunohistochemistry; Salivary Gland Neoplasms; Salivary Glands; Myoepithelioma; Carcinoma
PubMed: 36928733
DOI: 10.1007/s12105-022-01502-0