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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 2021Epithelial-myoepithelial carcinoma is an uncommon low-grade salivary gland carcinoma. It is classically characterized by biphasic tubular structures composed of inner... (Review)
Review
Epithelial-myoepithelial carcinoma is an uncommon low-grade salivary gland carcinoma. It is classically characterized by biphasic tubular structures composed of inner eosinophilic ductal cells and outer clear myoepithelial cells. In addition, epithelial-myoepithelial carcinoma sometimes shows various histologic features, including a cribriform pattern, basaloid appearance, and sebaceous differentiation. Because clear myoepithelial cells are also noted in other benign and malignant salivary gland tumors, the histologic variety and similarity with other tumor entities make the diagnosis of epithelial-myoepithelial carcinoma challenging. A recent analysis revealed that HRAS hotspot point mutations are specifically identified in epithelial-myoepithelial carcinoma and the assessment of given genes facilitate the correct diagnosis.
Topics: Diagnosis, Differential; Epithelial Cells; Humans; Myoepithelioma; Point Mutation; Prognosis; Proto-Oncogene Proteins p21(ras); Salivary Gland Neoplasms
PubMed: 33526226
DOI: 10.1016/j.path.2020.10.002 -
The American Journal of Surgical... Apr 2023Glioma-associated oncogene 1 ( GLI1 ) alterations have been described in pericytoma with t(7;12), gastroblastoma, plexiform fibromyxoma, and an emerging class of GLI1...
Glioma-associated oncogene 1 ( GLI1 ) alterations have been described in pericytoma with t(7;12), gastroblastoma, plexiform fibromyxoma, and an emerging class of GLI1 -rearranged or amplified mesenchymal neoplasms including "nested glomoid neoplasm". The immunophenotype of these tumor types is nonspecific, making some cases difficult to diagnose without sequencing. The utility of GLI1 immunohistochemistry (IHC) in distinguishing nested glomoid neoplasms and pericytomas with t(7;12) from morphologic mimics is unknown. To investigate the diagnostic value of GLI1 IHC, we determined its sensitivity and specificity in a "test cohort" of 23 mesenchymal neoplasms characterized by GLI1 alterations, including 12 nested glomoid neoplasms (7 GLI1 -rearranged, 4 GLI1 amplified, and 1 unknown GLI1 status), 9 pericytomas with t(7;12), 1 gastroblastoma, and 1 malignant epithelioid neoplasm with PTCH1 :: GLI1 fusion. GLI1 IHC was 91.3% sensitive in this cohort; all tumors except 2 pericytomas with t(7;12) expressed GLI1. GLI1 was also expressed in 1 of 8 (12%) plexiform fibromyxomas. Nineteen of 22 GLI1-positive tumors showed nuclear and cytoplasmic staining, while 3 showed nuclear staining only. GLI1 IHC was 98.0% specific; among morphologic mimics [40 well-differentiated neuroendocrine tumors, 10 atypical lung carcinoids, 20 paragangliomas, 20 glomus tumors, 20 solitary fibrous tumors, 10 Ewing sarcomas, 10 alveolar rhabdomyosarcomas (ARMS), 10 BCOR -altered sarcomas, 10 myoepitheliomas, 9 myopericytomas, 9 epithelioid schwannomas, 9 ossifying fibromyxoid tumors, 10 biphasic synovial sarcomas, 10 PEComas, 31 gastrointestinal stromal tumors, 10 inflammatory fibroid polyps, 11 pseudoendocrine sarcomas], 5 of 249 tumors expressed GLI1 (2 well-differentiated neuroendocrine tumors, 1 ARMS, 1 Ewing sarcoma, 1 BCOR -altered sarcoma). GLI1 IHC was also performed on a separate cohort of 13 molecularly characterized mesenchymal neoplasms in which GLI1 copy number gain was identified as a putatively secondary event by DNA sequencing (5 dedifferentiated liposarcoma [DDLPS], 2 adenosarcomas, 2 unclassified uterine sarcomas, 1 leiomyosarcoma, 1 ARMS, 1 intimal sarcoma, 1 osteosarcoma); 2 DDLPS, 1 ARMS, and 1 unclassified uterine sarcoma expressed GLI1. Lastly, because pleomorphic sarcomas sometimes show GLI1 amplification or copy number gain, GLI1 IHC was performed on a separate "pleomorphic sarcoma" cohort: GLI1 was expressed in 1 of 27 DDLPS, 1 of 9 leiomyosarcomas, and 2 of 10 pleomorphic liposarcomas, and it was negative in 23 well-differentiated liposarcomas and 9 unclassified pleomorphic sarcomas. Overall, GLI1 IHC was 91.3% sensitive and 98.0% specific for mesenchymal tumor types with driver GLI1 alterations among morphologic mimics. GLI1 expression was less frequent in other tumor types with GLI1 copy number gain. Given its specificity, in the appropriate morphologic context, GLI1 IHC may be a useful diagnostic adjunct for mesenchymal neoplasms with GLI1 alterations.
Topics: Humans; Immunohistochemistry; Zinc Finger Protein GLI1; Sarcoma, Ewing; Sarcoma; Liposarcoma; Soft Tissue Neoplasms; Neuroendocrine Tumors; Biomarkers, Tumor
PubMed: 36693363
DOI: 10.1097/PAS.0000000000002018 -
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 -
Virchows Archiv : An International... Aug 2023Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used in pathology for the assessment of melanocytic neoplasms; however, knowledge...
Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used in pathology for the assessment of melanocytic neoplasms; however, knowledge of its expression patterns in soft tissue tumors is limited. PRAME immunohistochemistry (clone QR005) was assessed on whole tissue sections of 350 soft-tissue tumors and mimics (> 50 histotypes). PRAME immunoreactivity was evaluated as follows: 0 "negative" (0% positive cells); 1+ (1-25% positive cells); 2+ (26-50% positive cells); 3+ (51-75% positive cells), and 4+ "diffuse" (> 75% positive cells). PRAME was expressed in 111 lesions (0 benign, 6 intermediate malignancy, and 105 malignant), including fibrosarcomatous dermatofibrosarcoma protuberans (2/4, 0 diffuse), NTRK-rearranged spindle cell neoplasm (2/4, 0 diffuse), atypical fibroxanthoma (1/7, 0 diffuse), Kaposi sarcoma (1/5, 0 diffuse), myxoid liposarcoma (11/11, 9 diffuse), synovial sarcoma (11/11, 6 diffuse), intimal sarcoma (7/7, 5 diffuse), biphenotypic sinonasal sarcoma (3/3, 1 diffuse), angiosarcoma (10/15, 6 diffuse), malignant peripheral nerve sheath tumor (9/12, 4 diffuse), pleomorphic rhabdomyosarcoma (2/3, 2 diffuse), alveolar rhabdomyosarcoma (2/6, 0 diffuse), embryonal rhabdomyosarcoma (7/7, 4 diffuse), undifferentiated pleomorphic sarcoma (2/12, 1 diffuse), leiomyosarcoma (2/15, 1 diffuse), clear cell sarcoma of soft tissue (1/10, 0 diffuse), low-grade fibromyxoid sarcoma (1/5, 0 diffuse), Ewing sarcoma (2/10, 1 diffuse), CIC-rearranged sarcoma (8/8, 4 diffuse), BCOR-sarcoma (2/5, 1 diffuse), melanoma (20/20, 14 diffuse), and thoracic SMARCA4-deficient undifferentiated tumor (5/5, all diffuse). All tested cases of spindle cell lipoma, dedifferentiated/pleomorphic liposarcoma, dermatofibrosarcoma protuberans, solitary fibrous tumor, inflammatory myofibroblastic tumor, myxoinflammatory fibroblastic sarcoma, nodular fasciitis, myxofibrosarcoma, epithelioid hemangioendothelioma, atypical vascular lesion, hemangioma, lymphangioma, vascular malformation, papillary endothelial hyperplasia, GIST, gastrointestinal clear-cell sarcoma, malignant melanotic nerve sheath tumor, neurofibroma, schwannoma, granular cell tumor, alveolar soft part sarcoma, epithelioid sarcoma, extraskeletal myxoid chondrosarcoma, myoepithelioma, ossifying fibromyxoid tumor, angiomatoid fibrous histiocytoma, PEComa, dermatofibroma, pleomorphic dermal sarcoma, and chordoma were negative. PRAME shows imperfect specificity in soft-tissue pathology but may serve as a diagnostic adjunct in selected differential diagnoses that show contrasting expression patterns.
Topics: Humans; Adult; Immunohistochemistry; Sarcoma; Soft Tissue Neoplasms; Sarcoma, Ewing; Skin Neoplasms; Transcription Factors; Fibrosarcoma; Melanoma; Diagnosis, Differential; Biomarkers, Tumor; DNA Helicases; Nuclear Proteins; Antigens, Neoplasm
PubMed: 37477762
DOI: 10.1007/s00428-023-03606-6 -
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 -
Acta Cytologica Feb 2024Salivary gland lesions possess diagnostic challenges on fine needle aspiration (FNA) material. They are relatively uncommon, yet present with a wide spectrum of... (Review)
Review
BACKGROUND
Salivary gland lesions possess diagnostic challenges on fine needle aspiration (FNA) material. They are relatively uncommon, yet present with a wide spectrum of cytomorphology. Herein, we review common salivary gland neoplasms, their cytomorphologic features, their diagnostic pitfalls, and ancillary studies helpful in achieving an accurate diagnosis.
SUMMARY
There are many cytomorphologic overlaps between benign and malignant salivary gland entities. Moreover, metaplasia, cystic changes, and degenerative changes are common findings adding to diagnostic dilemmas. These complicating factors contribute to a minute risk of malignancy in salivary gland lesions that are interpreted as benign on FNA. In rare cases, even malignant salivary gland neoplasms are misinterpreted as benign on aspirated material due to the many cytomorphologic overlaps. For example, benign and malignant neoplasms containing stroma such as myoepithelioma and adenoid cystic carcinoma may be misinterpreted as pleomorphic adenoma. Moreover, diagnosis of salivary gland neoplasms with basal cell features can be confusing on FNA materials; for example, basal cell adenoma can be misinterpreted as adenoid cystic carcinoma. Mucoepidermoid carcinomas have many different appearances on aspirated material due to variable amounts of mucin, degree of nuclear atypia, cellular content, and squamous metaplasia. Acinic cell carcinoma exhibits large cells with abundant cytoplasm on FNA, which can be mistaken for oncocytic cells in oncocytoma or Warthin tumor. Salivary duct carcinoma shows distinct features of malignancy and thus can be mistaken for secondary tumors involving the salivary glands or other malignant salivary gland tumors. The presence of tumor-associated lymphocytes is another underlying cause of misdiagnosis, especially when considering the differential diagnosis of an an intraparotid lymph node. Ancillary studies such as immunohistochemistry and molecular studies are gaining more attention to be utilized on FNA cases. PLAG1 immunostaining, CD117 , DOG1, mammaglobin, and androgen receptor (AR) are examples of commonly used immunostains in diagnosis of salivary gland lesions. MYB gene fusion , rearrangements of the MAML2 gene, ,and ERBB2/HER2 are examples of molecular alterations useful in diagnosis of salivary gland neoplasms. In conclusion, the aim of salivary gland cytology is to differentiate benign entities from the malignant ones and to prevent unnecessary aggressive treatments.
PubMed: 38417405
DOI: 10.1159/000538069 -
Journal of Gynecology Obstetrics and... Dec 2022We performed a systematic review in order to describe the clinical presentation, therapeutic management and outcomes of malignant myoepitelioma of the breast.
OBJECTIVES
We performed a systematic review in order to describe the clinical presentation, therapeutic management and outcomes of malignant myoepitelioma of the breast.
SEARCH STRATEGY
A systematic search of MEDLINE and EMBASE references from January 1980 to Marsh 2020 was performed. We included articles that reported cases of malignant breast myoepithelioma. Data from eligible studies were independently extracted onto standardized forms by two reviewers.
RESULTS
31 articles including 47 cases of malignant breast myoepithelioma and 3 other unpublished cases managed in our establishment were included in this systematic review. The average age at diagnosis was 60.7 years old [range 30-81]. The average size of the tumor was 46mm [range 10 -230]. 30 patients had a partial mastectomy and 18 a total mastectomy. Only 15% of patient (7/48) had an axillary sentinel lymph node biopsy of whom one was positive. 33% of patients (16/48) had an axillary lymph node dissection which was positive for one patient. 19% (n=9) had adjuvant radiotherapy and 15% (n=7) had adjuvant chemotherapy. 33% (n=10) of patients with partial mastectomy had at least one recurrence, versus 5.5% (n=1) after a total mastectomy. The average time between the diagnosis and the first recurrence was 25.4 months [range: 1-50]. 64% (n=7) had a second partial mastectomy and only 18% (n=2) had a total mastectomy. 27% of patient had chemotherapy after their first recurrence and 27% had radiotherapy if it was not received in first line treatment. 40% (n=4/10) of patients with partial mastectomy who recurred have had at least 2 breast recurrences. 28% (n=14) of all patients had distant metastases. 20% of patients (n=10) died whose 80% (n=8) had distant metastatic disease.
CONCLUSIONS
This systematic review provided a precise summary of the clinical characteristics and treatment of patients presenting with Malignant breast myoepithelioma in the past 40 years. We anticipate that these results will help inform current investigations and treatment.
Topics: Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Female; Breast Neoplasms; Mastectomy; Myoepithelioma; Mastectomy, Segmental; Axilla
PubMed: 36208828
DOI: 10.1016/j.jogoh.2022.102481 -
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