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The American Journal of Surgical... Oct 2018Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms that may show overlapping morphology and immunohistochemistry with uterine smooth muscle...
Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms that may show overlapping morphology and immunohistochemistry with uterine smooth muscle tumors. In this study, we evaluated the morphologic, immunohistochemical, and molecular features of 32 PEComas, including 11 with aggressive behavior. Two distinct morphologies were observed: classic (n=30) and those with a lymphangioleiomyomatosis appearance (n=2). In the former, patients ranged from 32 to 77 (mean: 51) years and 13% had tuberous sclerosis. Tumors ranged from 0.2 to 17 (mean: 5.5) cm with 77% arising in the corpus. Epithelioid cells were present in 100% and a spindled component was seen in 37%. Nuclear atypia was low (53%), intermediate (17%), or high (30%). Mitoses ranged from 0 to 36 (mean: 6) and 0 to 133 (mean: 19) per 10 and 50 high-power fields, with atypical mitoses present in 30%. Thin and delicate vessels were noted in 100%, clear/eosinophilic and granular cytoplasm in 93%, stromal hyalinization in 73%, necrosis in 30%, and lymphovascular invasion in 10%. All tumors were positive for HMB-45, cathepsin K, and at least one muscle marker, with most expressing melan-A (77%) and/or MiTF (79%). A PSF-TFE3 fusion was identified in one while another showed a RAD51B-OPHN1 fusion. Follow-up ranged from 2 to 175 (mean: 41) months, with 63% of patients alive and well, 20% dead of disease, 13% alive with disease, and 3% dead from other causes. In the latter group (n=2), patients were 39 and 49 years old, one had tuberous sclerosis, while the other had pulmonary lymphangioleiomyomatosis. Both tumors expressed HMB-45, cathepsin K, and muscle markers, but lacked TFE3 and RAD51B rearrangements. The 2 patients are currently alive and well. Application of gynecologic-specific criteria (≥4 features required for malignancy: size ≥5 cm, high-grade atypia, mitoses >1/50 high-power fields, necrosis, and lymphovascular invasion) for predicting outcome misclassified 36% (4/11) of aggressive tumors; thus, a modified algorithm with a threshold of 3 of these features is recommended to classify a PEComa as malignant.
Topics: Adult; Aged; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Biomarkers, Tumor; DNA-Binding Proteins; Epithelioid Cells; Female; Gene Fusion; Genetic Predisposition to Disease; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Middle Aged; Mitosis; Perivascular Epithelioid Cell Neoplasms; Phenotype; Predictive Value of Tests; Reproducibility of Results; Tumor Burden; Uterine Neoplasms
PubMed: 30001237
DOI: 10.1097/PAS.0000000000001119 -
Journal of Nippon Medical School =... 2019Pseudomyogenic hemangioendothelioma (PMHE) is a new entity. It is an intermediate soft tissue tumor clinically and/or histopathologically mimicking some other high-grade...
Pseudomyogenic hemangioendothelioma (PMHE) is a new entity. It is an intermediate soft tissue tumor clinically and/or histopathologically mimicking some other high-grade malignant tumors and some inflammatory diseases. We report a case of PMHE on the left plantar surface of a 28-year-old woman. Histopathological examination of the resected specimen revealed spindle and epithelioid cells with plump and atypical nuclei proliferated in the dermis and subcutaneous fat tissue with marked fibroplasia. Both spindle and epithelioid cells had abundant eosinophilic cytoplasm. Neoplastic cells were diffusely positive for AE1/AE3, CK7, vimentin, CD31, FLI-1, ERG, and INI-1. From those findings, we made the diagnosis of PMHE. We describe the main points of differentiation between PMHE and diseases that have similar clinical and/or histopathological findings, including cellular dermatofibroma, spindle cell squamous cell carcinoma, epithelioid sarcoma, epithelioid hemangioendothelioma, epithelioid angiosarcoma, nodular or proliferative fasciitis, and granulomatous fibrosing granulation tissue due to a ruptured epidermal cyst.
Topics: Adult; Antiporters; Diagnosis, Differential; Female; Hemangioendothelioma, Epithelioid; Humans; Keratins; Platelet Endothelial Cell Adhesion Molecule-1; Proto-Oncogene Protein c-fli-1; SMARCB1 Protein; Soft Tissue Neoplasms; Transcriptional Regulator ERG; Vimentin
PubMed: 31130564
DOI: 10.1272/jnms.JNMS.2019_86-209 -
World Neurosurgery Jul 2012Pituicytomas are rare tumors of the sellar region that are derived from specialized glial cells called pituicytes. They characteristically exhibit spindle-cell features... (Review)
Review
BACKGROUND
Pituicytomas are rare tumors of the sellar region that are derived from specialized glial cells called pituicytes. They characteristically exhibit spindle-cell features and fascicular or storiform patterns of growth. No other histological variants of this tumor have been described.
CASE DESCRIPTION
Here we report a diagnostically challenging case of pituicytoma in a 42-year-old man with a sellar mass arising from the pituitary stalk. On histological examination, the tumor displayed an epithelioid histoarchitecture with no characteristic spindle-cell or fascicular growth features. Strong immunopositivity for the pituicyte marker thyroid transcription factor-1 within tumor cells proved essential for diagnosing this unusual pituicytoma variant.
CONCLUSION
Pituicytomas may display epithelioid rather than fascicular or storiform histoarchitecture. Epithelioid pituicytoma variants may be diagnosed in cases such as ours in which both the clinical findings and immunohistochemical analysis suggest a tumor derived from pituicytes.
Topics: Adult; Biomarkers, Tumor; Craniotomy; Diagnosis, Differential; Epithelioid Cells; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Pituitary Gland; Pituitary Neoplasms
PubMed: 22120271
DOI: 10.1016/j.wneu.2011.09.011 -
The American Journal of Surgical... Apr 2018ACTB-GLI1 fusions have been reported as the pathognomonic genetic abnormality defining an unusual subset of actin-positive, perivascular myoid tumors, known as...
A Distinct Malignant Epithelioid Neoplasm With GLI1 Gene Rearrangements, Frequent S100 Protein Expression, and Metastatic Potential: Expanding the Spectrum of Pathologic Entities With ACTB/MALAT1/PTCH1-GLI1 Fusions.
ACTB-GLI1 fusions have been reported as the pathognomonic genetic abnormality defining an unusual subset of actin-positive, perivascular myoid tumors, known as "pericytoma with the t(7;12) translocation." In addition, GLI1 oncogenic activation through a related MALAT1-GLI1 gene fusion has been recently reported in 2 unrelated gastric tumors, namely plexiform fibromyxoma and gastroblastoma. Triggered by unexpected targeted RNA-sequencing results detecting GLI1-related fusions in a group of malignant neoplasms with round to epithelioid morphology, and frequently strong S100 protein immunoreactivity, we investigated their clinicopathologic features in relation to other known pathologic entities sharing similar genetics. On the basis of a combined approach of targeted RNA sequencing and fluorescence in situ hybridization screening, we identified 6 cases with GLI1 gene fusions, including 4 fused to ACTB, 1 with MALAT1 and 1 with PTCH1 gene. Patients had a mean age of 36 years at diagnosis (range, 16 to 79 y) and slight female predilection all except 1 tumor originated in the soft tissue. Microscopically, the tumors had a monomorphic epithelioid phenotype arranged in a distinctive nested or cord-like architecture, separated by thin septae and delicate capillary network. All except 2 cases were strongly positive for S100 protein, whereas being negative for SOX10, SMA, and EMA. Only 1 tumor showed focal cytokeratin positivity in rare cells. Although the tumors showed some resemblance to pericytic/glomus tumors or myoepithelial tumors, the immunoprofile was not supportive of either lineage. Moreover, in contrast to the benign course of so-called pericytoma with t(7;12), 3 patients in this series developed metastatic disease to either lymph nodes or lung. In fact the only patient with lung metastases showed a novel PTCH1-GLI1 gene fusion. It remains to be determined whether these tumors represent a clinically and immunohistologically distinct subset of pericytoma, or an altogether novel soft tissue sarcoma. Our findings open new opportunities for targeted therapy, as tumors with GLI1 oncogenic activation, and subsequent PTCH1 overexpression, might be sensitive to sonic hedgehog pathway inhibitors.
Topics: Actins; Adolescent; Adult; Aged; Biomarkers, Tumor; Biopsy; Bone Neoplasms; Epithelioid Cells; Female; Gene Fusion; Gene Rearrangement; Genetic Predisposition to Disease; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Male; Middle Aged; Neoplasm Metastasis; Patched-1 Receptor; Phenotype; RNA, Long Noncoding; S100 Proteins; Soft Tissue Neoplasms; Young Adult; Zinc Finger Protein GLI1
PubMed: 29309307
DOI: 10.1097/PAS.0000000000001010 -
Annual Review of Medicine Jan 2017Lymphangioleiomyomatosis (LAM) is a rare, low-grade, metastasizing neoplasm that arises from an unknown source, spreads via the lymphatics, and targets the lungs. All... (Review)
Review
Lymphangioleiomyomatosis (LAM) is a rare, low-grade, metastasizing neoplasm that arises from an unknown source, spreads via the lymphatics, and targets the lungs. All pulmonary structures become infiltrated with benign-appearing spindle and epithelioid cells (LAM cells) that express smooth-muscle and melanocyte-lineage markers, harbor mTOR-activating mutations in tuberous sclerosis complex (TSC) genes, and recruit abundant stromal cells. Elaboration of lymphangiogenic growth factors and matrix remodeling enzymes by LAM cells enables their access to lymphatic channels and likely drives the cystic lung remodeling that often culminates in respiratory failure. Dysregulated cellular signaling results in a shift from oxidative phosphorylation to glycolysis as the preferred mode of energy generation, to allow for the accumulation of biomass required for cell growth and tolerance of nutrient-poor, anaerobic environments. Symptomatic LAM occurs almost exclusively in females after menarche, highlighting the central but as yet poorly understood role for sex-restricted anatomical structures and/or hormones in disease pathogenesis. LAM is an elegant model of malignancy because biallelic mutations at a single genetic locus confer all features that define cancer upon the LAM cell-metabolic reprogramming and proliferative signals that drive uncontrolled growth and inappropriate migration and invasion, the capacity to exploit the lymphatic circulation as a vehicle for metastasis and access to the lungs, and destruction of remote tissues. The direct benefit of the study of this rare disease has been the rapid identification of an effective FDA-approved therapy, and the collateral benefits have included elucidation of the pivotal roles of mTOR signaling in the regulation of cellular metabolism and the pathogenesis of cancer.
Topics: Animals; Cell Death; Cell Proliferation; Estrogens; Humans; Lung Neoplasms; Lymphangioleiomyomatosis; Lysosomes; Neoplasm Invasiveness; Neoplasm Metastasis; Progesterone; Signal Transduction; TOR Serine-Threonine Kinases; Tuberous Sclerosis Complex 1 Protein; Tuberous Sclerosis Complex 2 Protein; Tumor Suppressor Proteins
PubMed: 28099079
DOI: 10.1146/annurev-med-050715-104245 -
The American Journal of Surgical... Aug 2022Identical TFE3-related gene fusions may be found in renal cell carcinoma and mesenchymal neoplasms such as alveolar soft part sarcoma and TFE3-rearranged perivascular...
Identical TFE3-related gene fusions may be found in renal cell carcinoma and mesenchymal neoplasms such as alveolar soft part sarcoma and TFE3-rearranged perivascular epithelioid cell tumor (PEComa). Among mesenchymal neoplasms, the ASPSCR1-TFE3 gene fusion has previously been described only in alveolar soft part sarcoma. We report 3 unusual mesenchymal neoplasms harboring the ASPSCR1-TFE3 gene fusion, the morphologic phenotype of which more closely matches PEComa rather than alveolar soft part sarcoma. All 3 neoplasms occurred in females ranging in age from 18 to 34 years and were located in the viscera (kidney, bladder, and uterus). All 3 contained nests of epithelioid cells bounded by fibrovascular septa. However, all were associated with hyalinized stroma, tight nested architecture, mixed spindle cell and epithelioid pattern, clear cytoplasm, and lacked significant discohesion. Overall, morphologic features closely resembled PEComa, being distinct from the typical alveolar soft part sarcoma phenotype. While none of the neoplasms labeled for HMB45, cytokeratin, or PAX8 all showed positivity for TFE3 and cathepsin K, and all except 1 were positive for smooth muscle actin. One patient developed a liver metastasis 7 years after nephrectomy. These cases bridge the gap between 2 TFE3-rearranged neoplasms, specifically alveolar soft part sarcoma and Xp11 translocation PEComa, highlighting the relatedness and overlap among Xp11 translocation neoplasms. While most TFE3-rearranged neoplasms can be confidently placed into a specific diagnostic category such as alveolar soft part sarcoma, PEComa, or Xp11 translocation renal cell carcinoma, occasional cases have overlapping features, highlighting the potential role that the cell of origin and the specific gene fusion play in the phenotype of these neoplasms.
Topics: Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Biomarkers, Tumor; Carcinoma, Renal Cell; Female; Gene Fusion; Humans; Intracellular Signaling Peptides and Proteins; Kidney Neoplasms; Perivascular Epithelioid Cell Neoplasms; Sarcoma, Alveolar Soft Part; Translocation, Genetic
PubMed: 35848761
DOI: 10.1097/PAS.0000000000001894 -
Journal of Clinical Medicine Apr 2021PEComa (perivascular epithelioid cell tumor) is a rare liver tumor. Decisions regarding patient management are currently based on a few small case series. The aim of...
PEComa (perivascular epithelioid cell tumor) is a rare liver tumor. Decisions regarding patient management are currently based on a few small case series. The aim of this study was to report the clinicopathological features of PEComa in order to provide guidance for management, complemented by our own experience. This retrospective observational study included all patients with PEComa who underwent surgical treatment in two departments between 2002 and 2020. A total of 20 patients were diagnosed with PEComa following histopathological examination. The age of the patients ranged from 21 to 73 years. The majority of patients were women (85%). In most patients, the tumors were incidental. In diagnostic studies, PEComas with high arterial vascularization have been described. Liver resection was the treatment of choice. There was only one postoperative complication. During histopathological evaluation, tumors were composed mostly of epithelioid cells, rarely with spindle cell components, thick-walled vessels, and adipocytes in different proportions. Melanocytic markers (HMB45, MelanA) and at least one smooth muscle marker were expressed in all tumors. Features suggestive of malignancy were found in three cases. In conclusion, PEComa is a rare liver tumor that is usually diagnosed incidentally. In radiological studies, tumors with high arterial vascularization are observed. Liver resection is the treatment of choice.
PubMed: 33919494
DOI: 10.3390/jcm10081756 -
Journal of Clinical Pathology Jul 1983The granulomatous inflammatory response is a special type of chronic inflammation characterised by often focal collections of macrophages, epithelioid cells and... (Review)
Review
The granulomatous inflammatory response is a special type of chronic inflammation characterised by often focal collections of macrophages, epithelioid cells and multinucleated giant cells. In this review the characteristics of these cells of the mononuclear phagocyte series are considered, with particular reference to the properties of epithelioid cells and the formation of multinucleated giant cells. The initiation and development of granulomatous inflammation is discussed, stressing the importance of persistence of the inciting agent and the complex role of the immune system, not only in the perpetuation of the granulomatous response but also in the development of necrosis and fibrosis.
Topics: Granuloma; Granuloma, Giant Cell; Humans; Macrophage Activation; Macrophages; Monocytes; Necrosis; Phagocytes; Phagocytosis; Pinocytosis
PubMed: 6345591
DOI: 10.1136/jcp.36.7.723 -
Medicine Jul 2016Perivascular epithelioid cell tumor (PEComa) is a rare entity with distinctive morphology and of expressing myomelanocytic markers. Gastrointestinal tract (GI) is one of... (Review)
Review
Perivascular epithelioid cell tumor (PEComa) is a rare entity with distinctive morphology and of expressing myomelanocytic markers. Gastrointestinal tract (GI) is one of the most common anatomic sites of origin and counts for 20% to 25% of all reported cases of perivascular epithelioid cell tumors not otherwise specified (PEComas-NOS). However, the biologic behavior of perivascular epithelioid cell tumors of gastrointestinal tract (GI PEComas-NOS) is still unclear. The aim of conducting this systematic review is to sum up what is known so far of the epidemiology, natural history, management and prognosis of GI PEComas-NOS.A systematic research was performed on PubMed and EMBASE using the following terms: ("perivascular epithelioid cell tumor" or "PEComa") and ("gastrointestinal tract" or "GI" or "oral " or "mouth" or "esophagus" or "gullet" or "gastric" or "stomach" or "duodenum" or "jejunum" or "ileum" or "cecum" or "colon" or "colorectal" or "sigmoid" or "rectum" or "anus" or "mesentery") up to December 1, 2015. Retrieved GI PEComas-NOS publications, which included these terms, contains case reports, case series to case characteristic researches.A total of 168 articles were reviewed, 41 GI PEComa-NOS English studies among which were retrieved for analysis. We reviewed epidemiology, natural history, management and prognosis of GI PEComa-NOS. Generally GI PEComa-NOS is believed to have women predomination. The most frequently involved location is colon with non-specific clinical signs. Pathologically, GI PEComas-NOS shows epithelioid predominance (70%), meanwhile coexpresses melanocytic and muscle markers characteristically, while immunohistochemistry is a useful tool for identify, which indicates that HMB-45 is regarded as the most sensitive reagent. Complete resection served as mainstay of treatment, while chemotherapy should be unanimously considered to apply in malignant cases. Eventually, it is necessary for closed and long-term follow-up with endoscope and imaging for ruling out local recurrence or distant metastasis of this tumor.GI PEComas-NOS lives with unclear behavior. There are still many unverified clinicopathological issues of GI PEComas-NOS that needs to be clarified. Further studies and analyses concerning this rare entity should be brought out. Thus, the randomized clinical researches (RCTs) are required to be conducted.
Topics: Biomarkers, Tumor; Diagnosis, Differential; Gastrointestinal Neoplasms; Humans; Perivascular Epithelioid Cell Neoplasms; Prognosis
PubMed: 27428182
DOI: 10.1097/MD.0000000000003890 -
Journal of Pharmacy & Bioallied Sciences Apr 2015Myoepithelial cells are a normal constituent of the salivary acini and ducts and are found between the epithelial cells and the basement membrane. Microscopically... (Review)
Review
Myoepithelial cells are a normal constituent of the salivary acini and ducts and are found between the epithelial cells and the basement membrane. Microscopically myoepithelial cells are thin and spindle-shaped and ultrastructurally they possess a number of Cytoplasmic processes that extend between and over the acinar and ductal-lining cells, and they show features of both smooth muscle and epithelium. They play a vital role during expulsion of saliva and regulates the electrolytic exchange. They also perform as tumor suppressors and are considered to play a very important role in differentiation of various salivary gland tumors and help in the diagnosis of tumors. Neoplastic myoepithelial cells in both benign and malignant tumors can take numerous forms including epithelioid, plasmacytoid, spindle and clear cell variant, and this variability largely accounts for difficulties in histopathological diagnosis.
PubMed: 26015706
DOI: 10.4103/0975-7406.155898