Apocrine carcinoma-and-malignant myoepithelioma in a dog: a case of simultaneous malignant progression of both luminal epithelium and myoepithelium.

A 9-y-old male Boxer dog developed a mandibular skin tumor, which histologically had a locally invasive growth pattern composed of bilayered structures of inner eosinophilic cuboidal tumor cells and outer clear polygonal tumor cells with cytoplasm containing glycogen granules. Both cell populations gradually changed from low-grade morphologic features to highly anaplastic ones. Immunohistochemically, the eosinophilic tumor cells were positive for cytokeratin 8, a useful marker for luminal epithelial cells. In contrast, the clear tumor cells expressed several myoepithelial markers, including α-smooth muscle actin, p63, and cytokeratin 14. Based on these histologic and immunohistochemical characteristics, we diagnosed this apocrine sweat gland tumor as a carcinoma-and-malignant myoepithelioma with high-grade transformation of both luminal and myoepithelial cells. Our case may be a helpful reference for the histogenesis of carcinoma-and-malignant myoepithelioma, in which both the luminal epithelial and myoepithelial components are malignant.

[Myoepithelial tumors of soft tissue: A case of mixed tumor]. / Tumeurs myoépithéliales des tissus mous : à propos d'un cas de tumeur mixte.

Myoepithelial neoplasms of soft tissue represent a rare entity which has been described only recently when compared to salivary gland tumors with whom they share histopathological and molecular features. The most common locations are the superficial soft tissues of the limbs and limb girdles. However, they can rarely occur in the mediastinum, abdomen, bone, skin and visceral organs. Benign forms (myoepithelioma and mixed tumor) are more frequent than myoepithelial carcinoma and the latter mostly affects children and young adults. Diagnosis is mainly based on histology, which shows a proliferation of myoepithelial cells of variable morphology with or without glandular structures in a myxoid background, and immunohistochemistry, which shows co-expression of epithelial and myoepithelial markers. Molecular tests are not mandatory, but in selected cases FISH analysis can prove useful as about 50% of myoepitheliomas show EWSR1 (or rarely FUS) rearrangements and mixed tumors show PLAG1 rearrangements. Here, we present a case of a mixed tumor of the soft tissue occuring in the hand with expression of PLAG1 in immunohistochemistry.

Intraoral exophytic lesion in an adolescent: A case report of myoepithelioma with unique clinical presentation.

Myoepithelioma is an infrequent benign tumor of the salivary glands, characterized by its composition of myoepithelial cells which can show different shapes and be arranged in various patterns with a well-circumscribed or encapsulated growth. This tumor commonly presents in adults as an asymptomatic swelling of the parotid gland, very rarely in minor salivary glands of children or adolescents, and even rarer in the buccal mucosa, with only six cases reported to date and only one of them presented in an adolescent. We present an additional case of myoepithelioma in the buccal mucosa of a 16-year-old male, with a novel clinical presentation as a non-submucosal exophytic mass. Immunohistochemically, neoplastic cells were positive for CK, S100, p63, and GFAP. The tumour was treated surgically, and the patient showed satisfactory evolution at 1 year of follow-up. The clinical and histopathological characteristics of the reported cases are discussed.

FOXO1 gene involvement in a non-rhabdomyosarcomatous neoplasm.

Myoepithelial neoplasms of soft tissue are rare tumors with clinical, morphological, immunohistochemical, and genetic heterogeneity. The morphological spectrum of these tumors is broad, and the diagnosis often requires immunostaining to confirm myoepithelial differentiation. Rarely, tumors show a morphology that is typical for myoepithelial neoplasms, while the immunophenotype fails to confirm myoepithelial differentiation. For such lesions, the term "myoepithelioma-like" tumor was introduced. Recently, two cases of myoepithelioma-like tumors of the hands and one case of the foot were described with previously never reported OGT-FOXO gene fusions. Here, we report a 50-year-old woman, with a myoepithelial-like tumor localized in the soft tissue of the forearm and carrying a OGT-FOXO1 fusion gene. Our findings extend the spectrum of mesenchymal tumors involving members of the FOXO family of transcription factors and point to the existence of a family of soft tissue tumors that carry the gene fusion of the OGT-FOXO family.

Metastatic Epithelial-Myoepithelial Carcinoma in a Female Presenting with Neck Mass and Lytic Lesion in Acetabulum: A Diagnostic Challenge on Cytology.

Epithelial-myoepithelial carcinoma (EMC) is a rare, low-grade, malignant salivary neoplasm. Establishing an accurate cytological diagnosis is often challenging owing to its rarity, bland cytologic appearance and variable representation of cell populations in the smears. The diagnostic struggle is more so when the aspiration is from a metastatic site with an unknown primary, as in such cases the list of differential diagnoses expands further. A 58-year-old female presented with a low-back pain from last one month. On examination, she also had a level III, right cervical swelling for the last 20 years. Radiology revealed a lytic lesion in the left acetabulum. She had undergone surgery 35 years ago for a right-sided upper neck swelling, the medical records of which were not available. Fine needle aspiration (FNA) from the cervical swelling was performed. The smears were cellular and showed predominantly dispersed, round to polygonal tumor cells with mild pleomorphism, eccentric nuclei, coarse chromatin, occasional nucleoli and moderate cytoplasm with some showing vacuolations. The cell-block section revealed tumor cells arranged in the form of tubules lined by dual layer of tumor cells without any chondromyxoid stroma. On immunocytochemistry, the luminal cells showed positivity for CK7 (epithelial marker) and the abluminal cells showed positivity for p63 (myoepithelial marker). Based on these features, a final diagnosis of metastatic epithelial-myoepithelial carcinoma was rendered. The present report highlights the characteristic cytomorphological and immunocytochemical features of EMC and reiterates the diagnostic accuracy of FNAC for diagnosis of such challenging cases.

Misinterpreted Myoepithelial Carcinoma of Salivary Gland: A Challenging and Potentially Significant Pitfall.

Myoepithelial carcinoma (MECA) is an underrecognized challenging entity with a broad morphologic spectrum. Misinterpreting MECA is not uncommon as distinguishing it from its mimics, especially cellular myoepithelial-rich pleomorphic adenoma (PA), can be difficult. We described 21 histologically challenging cases of MECAs (16 MECA ex-PA and 5 MECA de novo). All MECAs ex-PA were intracapsular or minimally invasive except for 3 cases. Eighteen (86%) were initially misinterpreted as benign neoplasms, including PA (10), atypical PA (5), and myoepithelioma (3). The remaining 3 were initially diagnosed as malignant (MECA ex-PA) but were histologically challenging. Histologic features that were found most helpful in recognizing the malignant nature of MECA included: uniformly cellular myoepithelial proliferation with an expansile nodular lobulated pattern (all cases) and alternate hypocellular and hypercellular zonal distribution (76% of cases). Among the 16 MECA patients with follow-up, 14 (87.5%) progressed: 10 developed local recurrence and 5 distant metastases. In contrast, only one of 33 patients with cellular PA (control group) recurred locally. Ten of the 14 MECAs that progressed were MECA ex-PA, and 12 (85%) had an initial benign diagnosis. Two patients with MECA ex-PA died of their disease; one had an initial diagnosis of PA. MECA is a histologically challenging entity that closely mimics PA and seems to carry a significant risk of recurrence. Areas of clonal appearing cellular myoepithelial growth with an expansile nodular lobulated pattern and zonal cellular distribution distinguish the majority of MECAs and may serve as useful diagnostic histologic features to differentiate MECA from its benign mimics.

Clear Cell Myoepithelial Carcinoma of the Upper Lip -A Rare Case Report.

Myoepithelial carcinomas are quite infrequent neoplasms and coupled with their diverse morphological appearance are interesting as far as diagnosis and management is concerned. They account for less than 1% of all salivary gland tumors. The variable morphologic appearance of myoepithelial carcinoma leads to a wide differential diagnosis, including primary salivary gland tumors and metastatic tumors. The prognosis of these tumors is not fair as they are locally aggressive and approximately one third of the patients die of the pathology. We report a case of clear cell variant of myoepithelial carcinoma in an unusual location, i.e. the upper lip. The treatment carried out was wide surgical resection. The patient was followed up for 2 years and was symptom free. The clear cell variant of myoepithelial carcinoma is extremely rare and only about 51 cases of this variant affecting the salivary glands have been reported worldwide so far.

[Clinicopathologic and molecular features of myoepithelial tumors of salivary glands].

Objective: To investigate the clinicopathological, and molecular characteristics of myoepithelial tumors (MTs) of salivary glands. Methods: A total of 37 MTs cases including 13 malignant epithelial tumors (MMTs) and 24 benign epithelial tumors (BMTs) of salivary glands were identified from the archives of the Department of Pathology, General Hospital of Eastern Theater Command, dating from 2006 to 2016. Clinical features, histological patterns, immunohistochemical characteristics and status of EWSR1 gene rearrangement by fluorescence in situ hybridization (FISH) analysis were reviewed in all cases. Results: Clinically, 37 MTs cases mainly occurred in the parotid glands, when most of the patients presented with painless masses. Of the 13 MMTs cases, male to female ratio was 7∶6, and the median age was 62 years old. Of the 24 BMTs cases, male to female ratio was 5∶7, and the median age was 54 years old. Immunohistochemically, 37 MTs cases were positive for CKpan, and at least one myoepithelial marker. Twenty six of 37 MTs cases were analyzable for the EWSR1 gene break by FISH. Based on the previous evaluation criterion, the EWSR1 translocation was detected in 4 cases of 11 MMTs, and 4 cases of 15 BMTs. According to the main histological composition of tumor cells, 4 EWSR1-positive MMTs covered 2 clear-cell cases and 2 epithelioid-cell cases, when 4 EWSR1-positive BMTs covered 2 clear-cell cases, 1 plasmacytoid-cell case, and 1 spindle-cell case. Conclusions: Males and females are affected equally. MTs express immunoreactivity for CKpan, and at least one myoepithelial marker. The EWSR1 rearrangement is present in a subset of MTs, with variable morphological characteristics, and has no statistical significance on clinical behavior.

Adenomyoepithelioma of the breast: case report and literature review.

Adenomyoepithelioma are uncommon tumors. The majority of them occur in women in the fifth and sixth decades who usually present with a self-palpated, solitary breast mass or a lesion identified on mammography. We report the case of adenomyoepithelioma of the breast with malignant transformation of both myoepitheliel and epithelial components diagnosed as malignancy during the preoperative stage in a seventy-six year old woman.

[Clinicopathologic characterization of malignant mixed tumor of the skin accompanied by eccrine porocarcinoma].

Objective: To investigate the clinicopathologic features, immunophenotype, pathological diagnosis and treatment of malignant mixed tumor (MMT). Methods: Clinical and pathological features including immunohistochemical phenotypes were analyzed in a case of MMT accompanied with eccrine porocarcinoma (EP) involving both hands, diagnosed definitely in January 2018 along with review of relevant literature. Results: A 64-year-old man presented with multiple rash on both hands for 4 years. Three lesions of 0.5 to 2.2 cm were removed for pathological evaluation. The pathological changes on little finger of left and right hands were MMT with EP, whereas that removed from the right ring finger was EP. MMT showed infiltrative growth with vascular wall invasion and consisted of epithelial (glandular or tube differentiation) and mesenchymal components (mucinous and/or cartilage stroma). The endothelial cells showed moderate to severe cytological atypia, nuclear pleomorphism and increased mitotic activity. The glandular component had histological characteristics of syringocarcinoma with moderately atypical chondrocytes but without myoepithelium. EP was composed of basal cells with visible vacuoles in cytoplasm and the presence of tubular and squamous differentiation, along with obvious atypia. Immunohistochemically cavosurface epithelium of glandular differentiation of MMT showed positivity for CK7, EMA and CD117. Myoepithelium showed S-100, CK5/6 and p63 positivity and stromal cells were positive for S-100. Differential diagnoses included metaplastic carcinoma, malignant myoepithelioma and atypical mixed tumor of skin. Conclusions: MMT with EP is extremely rare.The diagnosis of MMT depends on the morphologic features. Immunohistochemical staining is helpful for differential diagnosis. Surgical excision with safety margins is the treatment of choice. Complementary radiotherapy and/or chemotherapy is still controversial. The clinical course of MMT is deemed unpredictable and long-term follow-up is necessary.

A rare case of primary peripheral epithelial myoepithelial carcinoma of lung: Case report and literature review.

BACKGROUND: Primary salivary gland-type tumors of lung are rare. Epithelial-myoepithelial carcinoma (EMC) of the lung is a minor salivary gland-type tumor subtype. METHODS: We report a very rare case of EMC located in the peripheral left lower lobe that was diagnosed in a 58-year-old man and this is the first study in which we summarize all the patients with primary peripheral lung EMC concerned with the clinical features. Informed consent was obtained from the patient. RESULTS: Chest computed tomography displayed an anomalous soft tissue mass with slightly lobular borders in the peripheral segment of the left lower lobe and closed to the visceral pleura. The surgery was performed by using video-assisted thoracic surgery. Grossly, the tumor was solitary, well-circumscribed, and unencapsulated endobronchial lesion. A microscopic examination revealed that it was circumscribed, although the tumor borders may show single cells or clusters of cells proliferating away from the main tumor mass. The inner tubular layer showed epithelial cell characteristics, whereas the outer layer exhibited myoepithelial cell characteristics. Immunostaining for P40, P63, and cytokeratin 5/6 was positive. However, the anaplastic lymphoma kinase-V, thyroid transcription factor-1, synaptophysin, chromogranin A and napsin A were negative. CONCLUSIONS: Literature review showed that most of patients with peripheral EMC were asymptomatic. Computed tomography and magnetic resonance imaging scans are able to indicate the presence of peripheral EMC. Pathological analysis is an effective method to clarify the diagnosis. Surgery is a regular treatment method. To facilitate the preoperative diagnosis and avoid the misdiagnosis of such a rare disease, more cases will need to be reported.

Myoepithelioma-like Tumor of the Vulvar Region Presenting as a Nonmyxoid Spindle-Cell Neoplasm: A Potential Histologic Mimicker of Solitary Fibrous Tumor.

A new entity termed "myoepithelioma-like tumor of the vulvar region (MELTVR)" has been proposed as a rare mesenchymal neoplasm of the vulvar area. Histologically, MELTVRs are usually similar to soft tissue myoepitheliomas; however, they have a characteristic immunoprofile, including positivity for estrogen receptor and negativity for S100 protein, and loss of SMARCB1 expression. In this first known case report of MELTVR, the authors present a case of MELTVR that was histologically categorized in a nonmyxoid spindle-cell tumor group and resembled solitary fibrous tumor rather than soft tissue myoepithelioma.

Epithelial-myoepithelial carcinoma arising from the subglottis: a case report and review of the literature.

BACKGROUND: Epithelial-myoepithelial carcinoma is an extremely rare disease that usually occurs in the parotid gland but can occur in a variety of sites such as the nasal cavity, paranasal sinus, and base of the tongue. CASE PRESENTATION: We report a rare case of epithelial-myoepithelial carcinoma, which developed in the subglottic region. A 78-year-old Korean woman visited our hospital complaining of hoarseness, which had developed 1 month previously. Flexible laryngoscopy showed a round mass that blocked approximately 80 % of the tracheal diameter. Complete excision of the mass was carried out under general anesthesia, using a transoral approach. Epithelial-myoepithelial carcinoma was diagnosed following immunohistochemical analysis. CONCLUSIONS: We report a rare case of epithelial-myoepithelial carcinoma that occurred in the subglottic region. To the best of our knowledge, only one other case has been reported since this disease was first identified approximately 40 years ago.

[Salivary gland-type lung tumor: An update]. / Tumeurs de type glandes salivaires du poumon.

"Salivary gland-type" tumors arising from the bronchi and lung are rare but not exceptional entities. They are mostly represented by malignant entities such as cystic adenoid carcinoma, mucoepidermoid carcinoma and epithelial/myoepithelial carcinoma. Benign tumors are rare, mainly encompassing pleomorphic adenomas, which are to differentiate from mucous gland adenomas, another entity arising specifically from the peri-bronchial glands. These tumours develop in the proximal bronchi and are not associated with smoke abuse. Their main treatment is surgery. It is important to differentiate them from other broncho-pulmonary tumours as they do not share the same prognosis and therapeutic. This article will review the WHO 2015 classification of these tumours as well as recent updates from the literature to help define diagnosis criteria for these uncommon entities.

Expanding the Spectrum of Renal Tumors in Children: Primary Renal Myoepithelial Carcinomas With a Novel EWSR1-KLF15 Fusion.

We report the first 2 examples of primary renal myoepithelial carcinoma (MEC), both occurring in children. Both tumors had the unique morphologic features, immunophenotype, and EWSR1 gene rearrangements supporting the diagnosis. In keeping with the previous observations of an aggressive behavior in pediatric MEC, both cases presented with advanced local stage and distant metastases at the time of diagnosis. The EWSR1 translocation partner was identified as the Kruppel-like factor 15 (KLF15) gene in both tumors, and the novel EWSR1-KLF15 gene fusion transcripts were verified using reverse transcription polymerase chain reaction and Sanger dideoxy sequencing. So far, a role for KLF15 in carcinogenesis has not been established, in contrast to other members of the Kruppel-like family of transcription factors, and no rearrangements involving this gene have been documented to our knowledge. These findings expand the spectrum of pediatric renal tumors to include MEC. The characterization of novel EWSR1-KLF15 fusion transcripts carries important diagnostic implications, as well as clues to understand the pathogenesis of these neoplasms.

Thoracic Myoepithelial Tumors: A Pathologic and Molecular Study of 8 Cases With Review of the Literature.

Thoracic myoepithelial tumors (MTs) are a rare group of tumors showing predominant or exclusive myoepithelial differentiation. They are poorly characterized from both a morphologic and genetic standpoint, in particular features that separate benign from malignant behavior. We examined the histologic and immunohistochemical features of 8 primary thoracic MTs and performed fluorescence in situ hybridization for EWSR1, FUS, PLAG1, and HMGA2, as well as several partner genes. Half (4/8) of the MTs occurred in large airways, and 3 had infiltrative borders. All cases showed immunoreactivity for epithelial markers, in conjunction with S100 protein or myogenic markers. MTs showed morphologic characteristics analogous to MTs at other sites, with no tumors having ductal differentiation. Necrosis and/or lymphovascular invasion was present in 5 cases, with mitotic activity ranging from 0 to 6 mitoses/2 mm² (mean 1). Metastases occurred in 2 cases, and no patients died of disease. Gene rearrangements were identified in half of the cases, with EWSR1-PBX1, EWSR1-ZNF444, and FUS-KLF17 fusions identified in 1 case each and 1 case having EWSR1 rearrangement with no partner identified. No cases were found to have HMGA2 or PLAG1 abnormalities. Compared with fusion-negative tumors, fusion-positive tumors tended to occur in patients who were younger (50 vs. 58 y), female (1:3 vs. 3:1 male:female ratio), and demonstrated predominantly spindle and clear cell morphology. Using a combined data set of our case series with 16 cases from the literature, poor prognosis was significantly correlated with metastases (P=0.003), necrosis (P=0.027), and ≥5 mitoses/2 mm²/10 high-power field (P=0.005). In summary, we identify a subset of thoracic MTs harboring rearrangements in EWSR1 or FUS, and our data suggest that necrosis and increased mitotic activity correlate with aggressive clinical behavior.

Clinicopathological characteristics and cell cycle proteins as potential prognostic factors in myoepithelial carcinoma of salivary glands.

Myoepithelial carcinoma (MCA) is a rare malignancy of salivary glands that was included in the WHO Classification of Head and Neck Tumors in 1991. MCA has shown a broad spectrum of clinical outcomes, but attempts to identify prognostic markers for this malignancy have not resulted in significant progress. Conventional histopathological characteristics such as tumour grade, nuclear atypia, mitotic index and cell proliferation have failed to predict the outcome of MCA. In this study, we reviewed the histopathology of 19 cases of MCA focusing on nuclear atypia, mitotic count, tumour necrosis, nerve and vascular invasion and occurrence of a pre-existing pleomorphic adenoma in connection to the MCA. Histopathological characteristics and clinical information were correlated with the immunohistochemical expression of cell cycle proteins including c-Myc, p21, Cdk4 and Cyclin D3. The proportion of tumour cells immunoreactive for these markers and their intensity of staining were correlated with clinical information using logistic regression, Kaplan-Meier and Cox regression. Using logistic regression analysis, cytoplasmic c-Myc expression was associated with the occurrence of metastases (P = 0.019), but limitations of semi-quantitation of immunostaining and the limited number of cases preclude definitive conclusions. Our data show that the occurrence of tumour necrosis predicts poor disease-free survival in MCA (P = 0.035).

Cytopathology in the diagnostic appraisal of uncommon malignant neoplastic lesions.

Cytology and fine needle aspiration (FNA) cytology are accepted means of diagnosing and typing of common forms of malignant tumors. However, their usefulness for diagnosing less common neoplasms is not clearly established and this study was designed to examine this. We report four unusual cases of patients with malignant neoplasms in which cytology and fine needle aspiration cytology or aspiration biopsy (FNAC, FNAB) contributed significantly in establishing the diagnosis. These cases facilitate the diagnostic capabilities of cytology over a wide spectrum of neoplasms including rare lymphoproliferative disorders and carcinomas.

Myoepithelioma-like Tumors of the Vulvar Region: A Distinctive Group of SMARCB1-deficient Neoplasms.

We describe 9 tumors that resemble soft tissue myoepitheliomas but possess certain traits that do not fit perfectly into this category. These tumors, herein referred to as "myoepithelioma-like tumors of the vulvar region," occurred in the subcutis of the vulva and surrounding regions of adult women aged 24 to 65 years. Histologically, the tumors measured 2 to 7.7 cm and were well circumscribed, focally encapsulated, and lobulated. Tumor cells had an epithelioid to spindled shape, with fine amphophilic cytoplasm, and uniform nuclei with vesicular chromatin and nucleoli. The tumor stroma was relatively hypervascular, and comprised a mixture of myxoid and nonmyxoid components. Myxoid areas accounted for <5% to 95% of the tumor volume, wherein cells proliferated singly or in a loosely cohesive manner. In nonmyxoid areas, tumors cells grew in diffuse sheets or storiform arrangements. Immunohistochemically, all tested tumors were positive for vimentin, epithelial membrane antigen, and estrogen receptor; most tumors expressed actin. All tumors were negative for S100 protein, glial fibrillary acidic protein, and CD34. Cytokeratin expression was absent in all but 2 tumors, which showed rare positivity. SMARCB1 expression was deficient in all cases. EWSR1, FUS, and NR4A3 rearrangements were absent. All tumors were treated through surgery. Although 3 tumors regrew or recurred after intralesional excision, all 9 patients were alive without metastases at a mean follow-up of 66 months. Myoepithelioma-like tumors of the vulvar region constitute a distinct group of tumors, although future research is required to determine whether they are an unusual subtype of soft tissue myoepitheliomas or a separate disease.

A large mediastinal benign myoepithelioma effacing the entire hemithorax: case report with literature review.

BACKGROUND: Myoepithelial neoplasms, although sometimes encountered in soft tissues are described very rarely in mediastinum and lung. We reported a rare case of such a tumor which was very large in size and not connected to respiratory tree. CASE PRESENTATION: A 24 year old male presented with blunt chest pain and respiratory distress. A CT scan was performed which showed large heterogeneously enhancing soft tissue mass occupying the left hemithorax. It measures 18.5 X 15.8 X 7.6. Thoracotomy with excision of the tumor was done. Operative findings include multilobulated and nodular large glistening white tumor located in anterior mediastinum adherent to parietal pleura and effacing the pulmonary parenchyma. However tumor was not connected or seems to originate from trachea or lung. Microscopic sections show neoplastic lesion composed of nests, cords and trabeculae of small to medium sized cells with round nuclei and clear cytoplasm. Background showed myxoid appearance with areas of cartilaginous differentiation. Immunohistochemical expression of CKAE1/AE3, p63, ASMA, S100 and GFAP favored the diagnosis of benign myoepithelioma. CONCLUSION: Myoepithelial tumors are rare soft tissue tumors thought to arise from stem cells capable of divergent differentiation and occur anywhere in the body. Histopathologic recognition of these tumors is essential as these tumors may behave in a benign fashion despite large sizes.