Background
Epithelial–myoepithelial carcinomas are well recognized but rare neoplasms that occur most commonly in the salivary glands, where they constitute only 1% of primary tumors. At this site they show a spectrum of morphologic features ranging from a purely myoepithelial phenotype to tumors containing both well-formed glandular elements and myoepithelial cells, these sometimes being termed adenomyoepitheliomas. They show a spectrum of biologic activity ranging from benign lesions to highly aggressive carcinomas. Epithelial–myoepithelial carcinomas are also very rarely seen in other organs containing salivary-type seromucinous glands, including breast, sweat glands, and bronchi.
OUTLINE
EPIDEMIOLOGY CHARACTERIZATION INCIDENCE Rare
1% of salivary gland tumorsAGE 7th decade SEX Slight female predominance
DISEASE ASSOCIATIONS CHARACTERIZATION Epithelial-myoepithelial carcinoma arising in pleomorphic adenoma of the palate.
Li CY, Shirasuna K, Ishibashi H, Nakayama H, Kiyoshima T.
Kyushu University, Oral and Maxillofacial Surgery, Fukuoka, Japan.
Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2000 Oct;90(4):460-5 Abstract quote
A case of epithelial-myoepithelial carcinoma (EMC) in pleomorphic adenoma (PA) occurring in the palate of a 72-year-old woman is reported.
The tumor was composed of 2 different components, PA and EMC, accounting for approximately 40% and 60% of the whole tumor, respectively. The EMC showed multiple tubular or solid nests, which were separated by a basement membrane and consisted of variable proportions of 2 cell types, cuboidal epithelial cells positive for cytokeratin and clear myoepithelial cells positive for glial fibrillary acid protein, whereas the myoepithelial nests of PA intermingled with hyaline and myxoid stroma. The malignancy was demonstrated by convincing evidence of invasion into the submucosa, although the EMC component was mostly surrounded by the PA components.
An increased immunoreactivity of proliferating cell nuclear antigen in the EMC area in comparison to the PA area also suggested EMC arising in a PA.
PATHOGENESIS CHARACTERIZATION Intercalated duct hyperplasia: possible relationship to epithelial-myoepithelial carcinoma and hybrid tumours of salivary gland.
Chetty R.
Division of Anatomical Pathology, University of Natal School of Pathology and Laboratory Medicine, Durban, South Africa.
Histopathology 2000 Sep;37(3):260-3 Abstract quote
AIMS: The aims of this study were to ascertain the incidence of intercalated duct hyperplasia in association with cases of epithelial-myoepithelial carcinoma (EMC), and to explore a possible relationship between them and hybrid carcinomas of salivary glands.
METHODS AND RESULTS: Seven cases of EMC with sufficient surrounding non-tumour parotid were examined. Three cases contained foci of intercalated duct hyperplasia adjacent to the tumour. One of the cases was a hybrid tumour composed of EMC and mucoepidermoid carcinoma. The hyperplastic intercalated ducts formed multiple foci within the salivary parenchyma and were composed of bland, uniform ducts. Cytological atypia was not identified.
CONCLUSIONS: Intercalated duct hyperplasia may be a precursor lesion to EMC. Furthermore, it may also explain why EMC is frequently associated with other salivary gland carcinomas, so-called hybrid tumours, as well as sharing histological features with adenoid cystic carcinoma. Recognition of the latter is of particular importance because adenoid cystic carcinoma carries a poor prognosis.
Epithelial-myoepithelial carcinoma harboring p53 mutation.
Daa T, Kashima K, Gamachi A, Nakayama I, Yokoyama S.
1st Department of Pathology, Oita Medical University, Japan.
APMIS 2001 Apr;109(4):316-20 Abstract quote
A case of epithelial-myoepithelial carcinoma of the parotid gland harboring p53 mutation is reported.
The tumor removed from a 67-year-old Japanese female was composed of an organoid biphasic population of cells: inner dark epithelial cells were surrounded by clear myoepithelial cells. The cells were immunopositive for EMA and smooth muscle actin, respectively. Some of the epithelial cells formed solid nests. Immunostaining for proliferating cell nuclear antigen (PCNA) resulted in a higher percentage of labeled cells in the solid epithelial region than in the region with the more general biphasic pattern. Genetic analysis, including polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) and nucleotide sequencing, revealed a mutation in codon 207 (aspartic acid to glycine) of the p53 tumor-suppressor gene.
To our knowledge, this is the first report of a mutation in the p53 gene in an epithelial-myoepithelial carcinoma of the salivary gland.
GROSS APPEARANCE/
CLINICAL VARIANTSCHARACTERIZATION GENERAL VARIANTS LUNG
Bronchial epithelial-myoepithelial carcinoma.
Ru K, Srivastava A, Tischler AS.
Department of Pathology, New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA.
Arch Pathol Lab Med. 2004 Jan;128(1):92-4. Abstract quote
Epithelial-myoepithelial tumor is extremely rare as a pulmonary neoplasm. Only 20 cases have been reported to date, of which 14 were malignant. We report a case of intrabronchial epithelial-myoepithelial carcinoma in a 73-year-old man with a history of heavy smoking. The tumor was well-circumscribed and caused distal airway obstruction.
Histologically, the tumor showed glandular and solid architecture. The glands were composed of an inner layer of epithelial cells and an outer layer of myoepithelial cells. The solid areas consisted of spindle-shaped myoepithelial cells. Immunohistochemical staining was positive for p53 and c-Kit (CD117).
Focal atypia and increased mitotic activity were present, but no vascular invasion or nodal metastasis was identified.Pulmonary epithelial-myoepithelial tumor of unproven malignant potential: report of a case and review of the literature.
Pelosi G, Fraggetta F, Maffini F, Solli P, Cavallon A, Viale G.
Department of Pathology and Laboratory Medicine, European Institute of Oncology and University of Milan School of Medicine, Italy.
Mod Pathol 2001 May;14(5):521-6 Abstract quote
Epithelial-myoepithelial tumors of the lung are rare neoplasms whose biological behavior and clinical course still remain to be defined.
A case of epithelial-myoepithelial tumor of the lung arising from bronchial mucosa-submucosa and occurring as a polypoid lesion of the upper left bronchus in a 47-year-old man is reported. The tumor did not infiltrate the cartilaginous wall of the bronchus and showed a biphasic histological appearance with a double layering of epithelial and myoepithelial cells. Myoepithelial spindle cells with eosinophilic cytoplasm were also observed. Mitotic figures were very rare and necrosis absent. Immunohistochemical study for epithelial and muscular markers confirmed the presence of a double-cell component in the tumor, namely epithelial and myoepithelial. The patient is alive and well, with no evidence of recurrent or metastatic disease 6 months after surgery.
On the basis of the present case and the six previously reported cases, we suggest using the noncommittal term pulmonary epithelial-myoepithelial tumor of unproven malignant potential (PEMTUMP) for this type of neoplasm. In addition, we first introduce p63 as a novel marker for highlighting the myoepithelial cells of the respiratory tract and speculate on the role of these cells in the development of this unusual tumor.
Epithelial–Myoepithelial Carcinomas of the Bronchus
Laura G. Fulford, M.B.B.S. ; Yoshimasa Kamata, M.D. ; Koichi Okudera, M.D. ; Allan Dawson, F.R.C.Path. ; Bryan Corrin, F.R.C.Path. ; Mary N. Sheppard, F.R.C.Path. ; Nassif B. N. Ibrahim, F.R.C.Path. ; Andrew G. Nicholson, D.M.
From the Department of Histopathology (L.G.F., B.C., M.N.S., A.G.N.), Royal Brompton Hospital, London, U.K.; the Pathology Center (Y.K.) and Second Department of Internal Medicine (K.O.), Hirosaki University School of Medicine, Hirosaki, Japan; the Department of Histopathology (A.D.), Morriston Hospital, Swansea, U.K.; and the Department of Histopathology (N.B.N.I.), Frenchay Hospital, Bristol, U.K.
Am J Surg Pathol 2001;25:1508-1514 Abstract quote
Epithelial–myoepithelial carcinomas are very rare in the lung, and little is known about the relationship of their histologic features to prognosis.
We describe five primary pulmonary epithelial–myoepithelial carcinomas with details on clinical presentation, histology, and immunohistochemical profiles. We also reviewed the literature to detail further their prognosis. The patients' ages ranged from 33 to 57 years (average 51 years). The tumors were all endobronchial and the patients presented with symptoms or imaging features of airway obstruction. The tumors were completely resected; none showed nodal involvement. All five patients are alive and free of disease 4 months to 8 years (average 4.2 years) after surgery. Four tumors showed a mixed pattern of glands lined by a dual layer of cells and solid sheets of either spindle cells or clear cells, the glandular and solid components being present in variable proportions. The fifth tumor comprised purely spindle cells. The mitotic rate was <1/20 high power fields in both the glandular and spindle/clear cell components. In one case there was focal nuclear pleomorphism. The inner layer of the glands stained for cytokeratins and epithelial membrane antigen, and the outer layer for S-100 and smooth muscle actin. In one case the spindle cells stained for CD34.
A review of published cases shows the majority of tumors behave in an indolent fashion, the rare aggressive tumors being predominantly myoepitheliomatous. Nevertheless, the term epithelial–myoepithelial carcinoma is preferred because of their malignant potential. A high mitotic rate, tumoral necrosis, and nuclear pleomorphism appear to be adverse prognostic factors.
Epithelial-myoepithelial carcinoma of the lung: immunohistochemical and ultrastructural observations and review of the literature.
Wilson RW, Moran CA.
Department of Pulmonary and Mediastinal Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Hum Pathol 1997 May;28(5):631-5 Abstract quote
Epithelial-myoepithelial carcinoma is a rare low-grade malignant salivary gland neoplasm that most commonly occurs in the parotid gland but can also arise in minor salivary glands.
We report a case of a primary epithelial-myoepithelial carcinoma of the lung. The patient is a 55-year-old black woman who presented with increasing shortness of breath and productive cough of at least 3 months duration. A left lower lobe endobronchial lesion was identified radiographically. Surgical resection of the lesion was performed, obtaining a circumscribed, nonencapsulated 3.9 cm tan mass which was attached to the inner wall of the lateral basal segment bronchus. A biphasic proliferation of epithelial (cytokeratin positive; S-100 protein and muscle-specific actin negative) and myoepithelial (S-100 protein and muscle-specific actin positive with focal weak cytokeratin positive) cells was identified by immunohistochemical and ultrastructural analysis of formalin-fixed tissue. The patient is disease free 7 months after resection.
Pulmonary epithelial-myoepithelial carcinoma likely derives from the submucosal bronchial glands and should be added to the growing list of salivary gland-type neoplasms that may occur as primary pulmonary neoplasms. Because its histology is identical to salivary epithelial-myoepithelial carcinoma, pulmonary epithelial-myoepithelial carcinoma should be considered a low-grade malignant neoplasm and should be designated as epithelial-myoepithelial carcinoma is preference to other terms that may not convey its malignant potential. Although follow-up on reported cases is limited, lobectomy with negative bronchial margin should be curative.
NASAL CAVITY Epithelial-myoepithelial carcinoma arising in the nasal cavity: a case report and review of literature.
Jin XL, Ding CN, Chu Q.
Department of Pathology, Rul Jin Hospital, Shanghai Second Medical University, China.
Pathology 1999 May;31(2):148-51 Abstract quote
Epithelial-myoepithelial carcinoma is an uncommon, low-grade, malignant epithelial neoplasm composed of variable proportions of ductular cells and large, clear staining, myoepithelial cells arranged around the periphery of the ducts. About 120 cases have been reported in the world literature, most of which were located in salivary glands, except for a few cases occurring in unusual locations such as breast, lacrimal gland, nose, paranasal sinus, trachea, bronchus, and lung.
We here reported the second case of epithelial-myoepithelial carcinoma of the nasal cavity with extension to the nasopharynx. The patient was a 61 year old Chinese female with two month's history of progressive nasal obstruction. Histopathologically, the tumor showed typical myoepithelial and ductal cells biphasic differentiation, duct-like structure and infiltrating growth pattern. Some ductal cells showed the characteristics of oxyphilic cell, which had never been reported before. Recurrence and metastasis rates of epithelial-myoepithelial carcinoma varied from 35% to 50% and 8.1% to 25% respectively in different reports. The present case had neither recurrence nor metastasis twenty months after operation.
When epithelial-myoepithelial carcinoma is mainly composed of spindle myoepithelial cells, the differential diagnosis should include myoepithelioma, neurofibroma, leiomyoma and hemangiopericytoma.
Epithelial-myoepithelial carcinoma of the nasal cavity.
Lee HM, Kim AR, Lee SH.
Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul.
Eur Arch Otorhinolaryngol 2000;257(7):376-8 Abstract quote
A 22-year-old male presented with a 1-year history of nasal obstruction due to a polypoid mass in the right nasal cavity. Histopathologic examination revealed the tumor to consist of a mixture of a trabecular structure with a double-layered arrangement of inner dark cells and outer clear cells. Immunohistochemical examination showed the clear cells to be positive for alpha-smooth muscle actin and S-100 protein. Ultrastructural examination confirmed the myoepithelial cell origin. The tumor was excised and no recurrence or metastasis was found 40 months after surgery.
We describe here a rare case of epithelial-myoepithelial carcinoma arising from the nasal cavity, one of the most unusual locations.
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL Double cell proliferation with inner layer of neoplastic ductal cells associated with an outer layer of prominent clear neoplastic myoepithelial cells
Infiltrative margins and perineural invasion
May have sclerotic hyalinizing variant and clear cell dominant variant which is ductal poorOccasional cases with dedifferentiation
VARIANTS Epithelial-myoepithelial carcinoma of the parotid. A case of ductal-predominant presentation with cytologic, histologic and ultrastructural correlations.
Yang GC, Soslow RA.
Department of Pathology, New York University Medical Center, New York 10016, USA.
Acta Cytol 1999 Nov-Dec;43(6):1113-8 Abstract quote
BACKGROUND: The cytologic features of the usual type of epithelial-myoepithelial carcinoma (EMC) of the parotid, with myoepithelial cell predominance, is well described in the cytology literature. In contrast, the cytologic features of ductal-predominant-type EMC has not yet been reported.
CASE: An 82-year-old male presented with a 2.7-cm parotid mass of two years' duration. Fine needle aspiration smears stained with Diff-Quik showed cohesive tissue fragments outlined by metachromatic fibrils scattered in abundant, smooth, bluish background material. Ultrafast Papanicolaou stain revealed sharply outlined, large ductal cells with smooth, round to oval nuclei, prominent nucleoli and abundant vacuolated cytoplasm; the cells were arranged tridimensionally in occasional follicles that contained thick secretions. Neoplastic myoepithelial cells were occasionally seen at the periphery of tissue fragments, most commonly hidden underneath the neoplastic ductal epithelium at a slightly different focal plane; the cells had small, oval, dark nuclei and inconspicuous cell borders. The nuclear area and cell size of the neoplastic ductal cells was two and three times, respectively, that of neoplastic myoepithelial cells.
CONCLUSION: EMC, depending on the ratio of ductal to myoepithelial cell components, has different cytologic presentations. This case illustrates the ductal-predominant presentation of EMC.
High-grade carcinoma component in epithelial-myoepithelial carcinoma of salivary glands clinicopathological, immunohistochemical and flow-cytometric study of three cases.
Alos L, Carrillo R, Ramos J, Baez JM, Mallofre C, Fernandez PL, Cardesa A.
Department of Pathology, Hospital Clinic and IDIBAPS, University of Barcelona, Spain.
Virchows Arch 1999 Apr;434(4):291-9 Abstract quote
Three cases of epithelial-myoepithelial carcinoma (EMC) with coexisting areas of high grade carcinoma are reported. In two of the cases there was a previous recurrence, and in all three patients there had been a sudden increase in size before final surgery. T
he typical ductal and myoepithelial components of EMC showed the usual biphasic pattern and the expected immunophenotypes, with expression of wide spectrum cytokeratins, Cam 5.2 and EMA in the ductal part, and muscle-specific actin, smooth muscle actin, S-100 protein, vimentin and cytokeratins in the myoepithelial component. These areas also had a low mitotic count and low proliferation rate as measured by immunohistochemistry and by flow cytometry. Conversely, areas of high-grade tumour had the features of a large cell carcinoma, with focal mucin secretion in two cases. This high-grade component showed an epithelial immunophenotype in two cases, and was negative for all tested markers in the third one. The mitotic counts and the proliferation rates were much higher in these anaplastic areas. One of the patients died 3 months after treatment; another developed lymph node metastases 1 year later and was alive after 6 years of follow-up. The third patient was alive without evidence of disease 7 months after wide surgical resection of the tumour.
The possibility of anaplastic transformation in EMC makes thorough sampling mandatory in this type of neoplasm.
SPECIAL STAINS/IMMUNOPEROXIDASE/
OTHERCHARACTERIZATION SPECIAL STAINS IMMUNOPEROXIDASE Epithelial-myoepithelial carcinoma: an immunocytochemical study.
Palmer RM.
Oral Surg Oral Med Oral Pathol 1985 May;59(5):511-5 Abstract quote
An immunocytochemical study of epithelial-myoepithelial carcinoma, using antibodies to smooth muscle myosin, keratins, and type IV collagen, is presented. This rare tumor of salivary gland is composed of tubules and ductal structures, comprising an outer layer of clear cells that show myoepithelial differentiation and an inner layer of eosinophilic cells that show ductal differentiation.
The findings in this study correlate well with previous ultrastructural descriptions of this tumor.
Epithelial-myoepithelial carcinoma of parotid gland: a case report with immunohistochemical and ultrastructural studies.
Shuangshoti S, Lutigaviboon V, Kasantikul V.
Department of Pathology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
J Med Assoc Thai 1998 Sep;81(9):712-6 Abstract quote
A 66-year-old man presented with a painless mass of the parotid gland. Light and electron microscopic studies verified the basic nature of the tumor as epithelial-myoepithelial carcinoma, a low-grade malignant neoplasm of the salivary gland. Pathologically, there were two types of cells; the inner eosinophilic epithelial cells lining the ducts and the outer clear cells. The former cells displayed immunoreactivity for cytokeratin and ultrastructural features of apical microvilli and desmosome. The latter cells were positive for actin, S-100 protein, vimentin and the cytoplasm contained actin microfilaments. Such pathological findings were characteristic features of this rare tumor.
To our knowledge, this is the first reported case of EMC in Thailand.
The myoepithelial immunophenotype in 135 benign and malignant salivary gland tumors other than pleomorphic adenoma.
Prasad AR, Savera AT, Gown AM, Zarbo RJ.
Henry Ford Hospital, Detroit, MI 48202, USA.
Arch Pathol Lab Med 1999 Sep;123(9):801-6 Abstact quote
BACKGROUND: We have previously studied the immunoreactivity of 3 novel smooth muscle-specific proteins, alpha-smooth muscle actin, smooth muscle myosin heavy chains, and calponin, to assess myoepithelial differentiation in pleomorphic adenomas.
OBJECTIVE: To further expand our knowledge of myoepithelial differentiation in other benign and malignant salivary gland tumors.
DESIGN: Formalin-fixed paraffin sections of 135 salivary gland tumors with associated normal glands were stained with monoclonal antibodies using the avidin-biotin complex immunoperoxidase method and enzymatic and microwave heat-induced epitope retrieval.
RESULTS: In adenoid cystic carcinomas and epithelial-myoepithelial carcinomas, all 3 markers exclusively highlighted the myoepithelial cell components and the epithelial cells were entirely negative. No immunostaining was detected in canalicular adenomas, oncocytomas, Warthin tumors, acinic cell carcinomas, mucoepidermoid carcinomas, squamous cell carcinomas, and polymorphous low-grade adenocarcinomas. Salivary duct carcinomas and adenocarcinomas, not otherwise specified had a distinctive pattern of uniform periductal staining of reactive myofibroblastic cells, and in salivary duct carcinomas some ducts retained a peripheral immunoreactive myoepithelial cell layer.
CONCLUSION: Immunoreactivity for these 3 smooth muscle-specific proteins confirms the known neoplastic myoepithelial component of adenoid cystic carcinomas and epithelial-myoepithelial carcinomas. The consistently positive staining pattern in adenoid cystic carcinomas may be diagnostically useful in discriminating histologically similar but consistently negative polymorphous low-grade adenocarcinomas. Periductal linear staining in adenocarcinoma, not otherwise specified and salivary duct carcinomas is distinctive and appears to represent a tight cuff of myofibroblasts associated with the infiltrating glands.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Adenoid cystic carcinoma Basal cell carcinoma Low grade polymorphous adenocarcinoma
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