Department of Pathology, University Health Network, Toronto, Ontario, Canada.
Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland tumor of presumed intercalated duct origin with a low risk of metastasis and mortality. Factors shown to affect behavior include positive margins, vascular invasion, necrosis, and myoepithelial anaplasia. The latter category and dedifferentiated EMCs have been separated on the basis of presumed myoepithelial versus ductal origin, respectively. Three additional cases of typical EMC with transition to high-grade carcinoma are presented. Two of the tumors were stained with CAM5.2, 34betaE12, cytokeratin 14, p63, S100, calponin, smooth muscle actin, and muscle-specific actin. All tumors showed a gradual transition to a high-grade carcinoma from an EMC, each composed of clear cells even in the high-grade regions. One case also showed a discrete area with ductal lumina and another had plasmacytoid morphology. Squamous differentiation was seen in all cases as well. A consistent immunostaining pattern was not noted. Areas with focal lumina were diffusely positive for CAM5.2 only. Areas with clear cells showed patchy S100 positivity only, whereas cytokeratin 14 and 34betaE12-stained squamous pearls. The case with plasmacytoid morphology was diffusely positive for p63. No immunoexpression was noted with smooth muscle actin, muscle-specific actin, or calponin. It was not possible to convincingly separate the high-grade component in these cases into ductal dedifferentiated EMC versus myoepithelial. Recently, there has been a move to abandon the term "dedifferentiation" in favor of "high-grade transformation" in other salivary gland malignancies. We report these 3 such cases, review the literature and propose that these lesions be regarded as "EMC with high-grade transformation."
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*Department of Pathology, University Health Network daggerDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada double daggerDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA section signDepartment of Pathology, Cleveland Clinic Foundation, Cleveland, OH.
Intercalated duct lesions (IDLs) are rare, poorly understood and not well-studied lesions that have been associated with a small number of epithelial-myoepithelial carcinomas (EMC) and basal cell adenomas. To examine the nature of IDLs and their association with salivary gland tumors, we reviewed 34 lesions in 32 patients. The IDLs were stained with CK7, estrogen receptors (ER), progesterone receptors, lysozyme, S100, calponin, and CK14. The patients ranged in age from 19 to 80 years (mean 53.8) with a 1.7:1 female predominance. The majorities of IDLs were parotid lesions (82%), were small and nodular (average size 3.1 mm) and showed 3 architectural patterns: hyperplasia (20), adenoma (9), and hybrid forms (5). In 59% of cases, IDLs were seen in conjunction with another salivary gland tumor, most commonly basal cell adenoma (8 cases), followed by EMC (3 cases). One case showed a combination of intercalated duct hyperplasia and basal cell adenoma. The IDLs stained diffusely with CK7 (100%) and S100 (73%) and focally for ER (91%) and lysozyme (100%). Calponin and CK14 highlighted a thin myoepithelial cell layer around all ducts (100%). Normal intercalated ducts were also consistently positive for CK7 and lysozyme, and focally for ER, but were S100 negative. In summary, IDLs have a variety of patterns ranging from hyperplasia to adenoma with hybrid lesions and share morphologic and immunophenotypic features with normal intercalated ducts. There is an association with basal cell adenomas and EMC, which lends credence to their role as a putative precursor lesion.
Head Neck Pathol. 2012 Jul 17;: 22801997
Equivocal p16 Immunostaining in Squamous Cell Carcinoma of the Head and Neck: Staining Patterns are Suggestive of HPV Status.
Department of Laboratory Medicine and Pathobiology, University Health Network, University of Toronto, Toronto, ON, Canada.
p16 immunohistochemistry (IHC) is commonly used as a surrogate marker for human papillomavirus (HPV) detection in squamous cell carcinomas of the head and neck (SCCHN). However, the HPV status of tumors not staining strongly for p16 is difficult to interpret and may require the use of PCR, not available in all laboratories, as a final arbiter. We aim to determine if staining pattern in equivocal p16 staining and correlation to the percentage of positively stained tumor cells is predictive of HPV status. A retrospective review was performed on all SCCHN that underwent p16 IHC and PCR in our institution from 2007 to 2010. Descriptors of staining pattern in the original IHC report were retrieved. All available IHC slides were reviewed and reclassified using consensus staining pattern descriptors. Original and reclassified descriptors were compared to the final PCR HPV status for statistical significance using the χ(2) test. An estimate of the percentage of tumor cells that showed any form of staining was performed. Thirty-two SCCHN cases that underwent PCR HPV testing had equivocal p16 IHC results. Twenty-six cases available for review were reclassified into four staining patterns. Comparing age, sex, tumor site and diagnosis to HPV PCR status showed no statistically significant findings. However, comparing original descriptors to HPV status was statistically significant with isolated staining associated with negative HPV status (p = 0.0002). Analysis using reclassified descriptors showed strong association of membranous/cytoplasmic staining of isolated cells with negative HPV status and faint, diffuse nuclear and cytoplasmic staining with positive HPV status (p = 0.00006). HPV-negative cases with the former pattern had no more than 30 % positively-stained tumor cells and HPV-positive cases with the latter pattern had 50-90 % positively-stained cells. Our results suggest that pattern of staining in p16 IHC is associated with HPV status. For instance, a diffuse nuclear and cytoplasmic staining pattern, regardless of intensity, is associated with HPV positivity. The HPV-positive cases determined by staining pattern were also associated with a higher percentage of stained tumor cells.
Calretinin staining facilitates differentiation of olfactory neuroblastoma from other small round blue cell tumors in the sinonasal tract.
Department of Pathology, Capital District Health Authority, Dalhousie University, Halifax, NS, USA.
OBJECTIVE Olfactory neuroblastoma (ONB) is an uncommon malignant tumor of the sinonasal tract and has a wide histologic differential diagnosis that includes other small round blue cell tumors (SRBCTs). Even with the use of immunohistochemistry (IHC), the correct diagnosis may be difficult, especially in small biopsies. The purpose of this study is to determine the usefulness of calretinin and p63 as an aid to distinguish ONB from other sinonasal SRBCTs. METHODS IHC staining for calretinin and p63 was performed on 21 specimens diagnosed as ONB and on 42 other sinonasal SRBCTs. Specimens were retrieved from the files of the QEII HSC, Halifax and UHN, Toronto. RESULTS All but 1 ONB (20 of 21) showed calretinin staining, with 15 of 21 showing staining in >75% of the tumor area and 18 of 21 showing moderate-to-strong staining intensity. Only pituitary adenomas (3 of 3) and a single case of small cell carcinoma, neuroendocrine type (1 of 2), showed a similar staining pattern. None of the ONBs showed staining for p63. P63 was positive in all cases of nonkeratinizing squamous cell carcinoma (2 of 2) and in single cases of mantle cell lymphoma (1 of 1) and poorly differentiated neuroendocrine carcinoma (1 of 1); however, it inconsistently stained diffuse large B-cell lymphoma (4 of 5), extranodal NK/T-cell lymphoma, nasal type (1 of 4), sinonasal undifferentiated carcinoma (1 of 6), and Ewing sarcoma/primitive neuroectodermal tumor (2 of 6). CONCLUSIONS Calretinin appears to be a useful marker to distinguish ONBs from other SRBCTs of the sinonasal tract, particularly when staining is moderate/strong and extensive. The calretinin-positive, p63-negative phenotype is fairly specific for ONB. The addition of these 2 IHC stains may aid in the diagnosis of sinonasal SRBCTs that are poorly differentiated, have inconclusive conventional IHC, or are found in small biopsies.
Mammary analog secretory carcinoma of salivary gland origin with the ETV6 gene rearrangement by FISH: expanded morphologic and immunohistochemical spectrum of a recently described entity.
Department of Pathology, University Health Network, University of Toronto, Toronto, ON, Canada.
Mammary analog secretory carcinoma (MASC) is a recently described tumor predominantly arising in the parotid gland. These tumors represent locally invasive malignancies with microcystic architecture, low-grade nuclei, and granular pink vacuolated cytoplasm. They display strong vimentin and S100 positivity and harbor an identical t(12;15)(p13;q25) to their breast counterpart, leading to a ETV6-NTRK3 fusion oncogene. These features help exclude the most important differential diagnostic considerations, namely, acinic cell carcinoma (AciCC) and low-grade cystadenocarcinoma, not otherwise specified. Here we present a series of 7 recent examples of MASC, which showed features not previously described. These 7 cases were observed in patients ranging in age from 14 to 77 years (mean, 40 y), occurred almost exclusively in male patients (6:1), and showed >50%(4 of 7 cases) involvement of the oral cavity, with only 2 arising in the parotid. The remaining case is the first reported in the submandibular gland. The tumors showed a variety of patterns including single macrocysts, combined macrocystic and microcystic spaces, and solid architecture. They showed prominent hobnailing in the cystic areas. Secretions within the cysts and tubular areas tended to be positive for periodic acid schiff, periodic acid schiff diastage and mucicarmine, the latter also showing occasional intracytoplasmic mucin droplets, a feature not previously recognized. One case showed prominent mucinous differentiation, which, coupled with high-molecular-weight keratins (HMWK) positivity, mimicked mucoepidermoid carcinoma (MEC). The tumors were generally positive for HMWK (6 of 7), S100 (5 of 7), vimentin, CK19, and other epithelial markers. The finding of duct involvement, proven with an incomplete p63-positive basal layer surrounding a minority of tumor cell nests and cysts, raised the possibility of a ductal epithelial origin for MASC. Alternatively, this could represent secondary ductal involvement by tumor. All cases showed rearrangement of the ETV6 gene by fluorescence in situ hybridization, confirming the diagnosis of MASC. These findings reinforce MASC as a unique low-grade salivary gland tumor entity with morphologic overlap with AciCC, MEC, and cystadenocarcinoma.
Cribriform adenocarcinoma of minor salivary gland origin principally affecting the tongue: characterization of new entity.
Alena Skalova, Radek Sima, Jana Kaspirkova-Nemcova, Roderick H W Simpson, Goran Elmberger, Ilmo Leivo, Silvana Di Palma, Tomas Jirasek, Douglas R Gnepp, Ilan Weinreb, Bayardo Perez-Ordoñez, Petr Mukensnabl, Boris Rychly, Petr Hrabal, Michal Michal
Department of Pathology, Charles University Prague, Faculty of Medicine in Pilsen, Pilsen, Czech Republic. email@example.com
We present a series of 23 cases of a distinctive, hitherto poorly recognized low-grade adenocarcinoma, with several histologic features reminiscent of papillary carcinoma of the thyroid, and which mostly but not exclusively occurs in the tongue. All the tumors were unencapsulated and were divided into lobules that were composed mainly of cribriform and solid growth patterns. Therefore, we propose the name "cribriform adenocarcinoma of minor salivary gland origin (CAMSG)." All the patients were adults with a mean age at diagnosis of 55.8 years (range, 25 to 85 y). Fourteen of the 23 tumors were localized in the tongue, 3 in the soft palate, 2 in the retromolar buccal mucosa, 3 in the lingual tonsils, and 1 in the upper lip. Fifteen patients of 23 had synchronous metastases in the cervical lymph nodes at the time of diagnosis, bilateral in 3 cases. In 3 patients, the nodal metastasis was the first evidence of disease, later investigation revealing primary neoplasms in the base of tongue and tonsil, respectively. In addition, 1 patient developed a cervical lymph node metastasis 8 years after excision of a primary tumor of the tongue. Data on treatment and follow-up were available in 14 cases. The patients were treated by radical excision with clear margins (12 cases) or by simple excision (2 cases). Neck dissection was performed in 10 patients; 9 received radiotherapy, but none were treated by chemotherapy. Clinical follow-up ranged from 2 months to 13 years (mean, 6 y and 5 mo). Twelve patients are alive with no evidence of recurrent or metastatic disease after treatment, 1 patient died 2 years after surgery without evidence of tumor, and 1 patient is alive with recurrent tumor of the palate.
EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland.
Cristina R Antonescu, Nora Katabi, Lei Zhang, Yun Shao Sung, Raja R Seethala, Richard C Jordan, Bayardo Perez-Ordoñez, Cherry Have, Sylvia L Asa, Iona T Leong, Grace Bradley, Hagen Klieb, Ilan Weinreb
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. firstname.lastname@example.org
Hyalinizing clear-cell carcinoma (HCCC) is a rare, low-grade salivary gland tumor with distinctive clear-cell morphology and pattern of hyalinization as well as focal mucinous differentiation. However, histological overlap exists with other salivary gland tumors, such as epithelial-myoepithelial carcinoma (EMCa), salivary myoepithelial carcinoma, and mucoepidermoid carcinoma (MEC). The potential relationship between HCCC and its morphological mimics has not been yet investigated at the genetic level. In this study, we conducted a molecular analysis for the presence of rearrangements in MAML2, commonly seen in MECs, and EWSR1, involved in "soft tissue myoepithelial tumors"(SMET) by fusion with POU5F1, PBX1, or ZNF444. Fluorescence in situ hybridization (FISH) was performed on 23 HCCC cases for abnormalities in MAML2, EWSR1, FUS, POU5F1, PBX1, and ZNF444. FISH for MAML2 was negative in all cases (0 of 14), including those with mucinous differentiation (0 of 7). An EWSR1 rearrangement was identified in 18 of 22 HCCCs (82%), while no break-apart signals were seen in FUS, POU5F1, PBX1, or ZNF444. 3'RACE on an EWSR1 rearranged HCCC identified an EWSR1-ATF1 fusion, which was confirmed by RT-PCR. ATF1 involvement was further confirmed by FISH analysis in 13 of 14 EWSR1-rearranged HCCC cases (93%). In contrast, all control cases tested, including among others 5 EMCa and 3 MEC with clear cells, were negative for EWSR1 and ATF1 rearrangements. The presence of EWSR1-ATF1 fusion in most HCCCs reliably separates these tumors from its histological mimics. The distinction from MEC is particularly important, as conventional MEC grading schemes overgrade these indolent HCCCs, potentially impacting on treatment.
Non-small cell neuroendocrine carcinoma of the sinonasal tract and nasopharynx. Report of 2 cases and review of the literature.
Department of Pathology, University Health Network, 200 Elizabeth Street, Toronto, Ontario, Canada.
Non-small cell neuroendocrine carcinomas (NSNECs) of the sinonasal tract are rare. Due to their rarity, the clinical and pathologic characteristics of these neoplasms are not adequately understood. We report two additional examples of NSNEC. The patients were male, 67- and 34-year-old. The first had a tumor involving left ethmoid sinus and nasal cavity and the second, a neoplasm involving nasopharynx, sphenoid sinus, with bilateral involvement of cavernous sinuses. Both tumors were composed of small to medium size cells showing round nuclei with finely dispersed chromatin and small to inconspicuous nucleoli. One case was characterized by variable size individual and confluent nests while the second demonstrated patternless sheets only. One case had punctate necrosis and a mitotic rate of 10-11/10 hpf whereas the second did not have necrosis and the mitotic rate was only 1-2/10 hpf. Both tumors were positive for keratins, CD56, and NSE. One case was positive for chromogranin and the second for synaptophysin. One patient is alive and free of disease 4 years after external beam radiotherapy. The second is alive with locally advanced disease 7 years after radiotherapy and chemotherapy. The literature suggests that NSNECs are a heterogenous group of neoplasms with a morphologic spectrum encompassing tumors resembling "atypical carcinoids", neoplasms composed of large cells akin to large cell neuroendocrine carcinomas, and tumors with glandular and goblet cell differentiation reminiscent of "goblet cell carcinoids". Other cases do not show specific features and are probably best regarded as "neuroendocrine carcinoma, NOS". More studies are needed to better define the histopathologic spectrum of these lesions and to develop a clinically relevant classification.
Department of Pathology, University Health Network, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada. email@example.com
CONTEXT:-Epithelioid hemangioendothelioma (EHE) is a vascular neoplasm that occasionally is difficult to distinguish from primary/metastatic carcinomas, particularly when EHEs express keratins. We recently encountered an EHE with strong CD10 positivity mimicking renal cell carcinoma. OBJECTIVE:-To examine sensitivity and specificity of CD10 in EHE. DESIGN:-Nine EHEs were stained with keratins, factor VIII, CD31, CD34, and CD10. Mimics of EHE were also retrieved and stained with CD10. RESULTS:-The EHE patients included 5 men and 4 women. Patients ranged in age from 24 to 74 years. Tumors were located in liver (3), skin (2), lung/pleura (2), and sternomastoid and mediastinum (1 each). Two had skin metastases. All EHEs were positive for vascular markers. A total of 7 of 9 primary tumors expressed cytoplasmic and intracytoplasmic luminal CD10. The 2 skin metastases were positive, whereas 2 primary skin EHEs were negative. Of the mimics, CD10 showed staining in 7 of 23 cases: 3 of 3 renal cell carcinomas, 1 of 7 other carcinomas, 2 of 3 epithelioid angiosarcomas, 1 of 3 melanomas, 0 of 3 mesotheliomas, and 0 of 4 epithelioid hemangiomas. CONCLUSIONS:-CD10 has a sensitivity of 78%(confidence interval, 63.6%-92.4%) and specificity of 70%(confidence interval, 54%-85.9%) for EHE. There is a growing list of tumors that show expression of CD10. Pathologists should be aware of this diagnostic pitfall.
Nodular fasciitis of the head and neck region: a clinicopathologic description in a series of 30 cases.
Department of Pathology, University Health Network and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Nodular fasciitis (NF) is a reactive lesion composed of fibroblasts/myofibroblasts and most commonly found in extremities and trunk. NF has been described in the head and neck region (HNR) in 13-20% of cases. It is our impression based on consultation experience that many pathologists do not consider NF in the differential diagnosis of soft tissue masses arising in the HNR. Moreover, it is common for these lesions to be incompletely excised, leading to additional challenges in diagnosis. We describe 30 cases of NF of the HNR in order to focus attention on this frequently overlooked diagnosis. While they had the typical histologic features of NF, the lesions had a tendency for smaller size, increased skeletal muscle involvement (30%) compared to fasciitis elsewhere in the body and diffuse and strong actin expression. Follow up demonstrated one recurrence (7.1%) higher than reported elsewhere in the body. These latter features may add to the challenge in diagnosing NF in these locations. Weinreb I, Shaw AJ, Perez-Ordoñez B, Goldblum JR, Rubin BP. Nodular fasciitis of the head and neck region: a clinicopathologic description in a series of 30 cases.
*Department of Pathology, University Health Network and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada daggerDepartment of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA double daggerDepartment of Pathology, Cleveland Clinic Foundation, Cleveland, OH.
Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy. Oncocytic MEC (OMEC) has been rarely reported with previous cases suggesting they are largely cystic low-grade neoplasms with a favorable prognosis. The differential diagnosis of OMEC includes numerous oncocytic/"oncocytoid" neoplasms. Some are benign while others are aggressive. Recent evidence suggests that p63 is a reliable marker in the diagnosis of conventional MEC but has not been explored in OMEC. We searched the archives of various institutions for examples of OMEC to re-appraise the grade, and to evaluate p63 immunohistochemistry as a tool to separate OMEC from its potential mimics. A total of 12 cases were identified. There were 6 males and 6 females with an age range of 30 to 79 years. Most occurred in the parotid (9) with 1 each in the sublingual gland, hard palate and neck. They showed minimal cystic content and were infiltrative and solid tumors spanning all grades. All tumors had focal mucin production and were composed almost exclusively of oncocytic cells with 2 cases demonstrating conventional MEC areas. All 6 cases tested showed the majority of oncocytic cells staining with p63 in a diffuse pattern, demonstrating its utility in the diagnosis of OMEC. Of the 6 cases with follow-up information, 1 case had local recurrence 8 years after the initial surgery. Three cases showed skin or bone invasion. None had lymph node/distant metastases. In summary, OMEC behaves as a low-grade tumor, and is diffusely positive for p63, which may aid in its differential diagnosis.
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Pathol Res Pract. 2012 May 31;: 22658481
CD10 and HHF35 actin in the differential diagnosis between Collagenous Spherulosis and Adenoid-Cystic Carcinoma of the breast.
Department of Sciences for Health Promotion, Section of Anatomic Pathology, University of Palermo, Italy.
Collagenous Spherulosis (CS) and Adenoid-Cystic Carcinoma (AdCC) of the breast consist of cribriform proliferations of epithelial and myoepithelial cells with an immunophenotypic overlap of some myoepithelial markers, such as p63 and smooth muscle actin (SMA). To our knowledge, CD10 and HHF35 actin have not been assessed in the differential diagnosis of these two breast lesions. We performed an immmunohistochemical study on 6 cases of CS and 9 cases of AdCC. We found CD10, muscle-specific actin (HHF35), Estrogen and Progesterone receptors (ER and PR) to be strongly expressed in CS, but not in AdCC; C-kit was diffusely positive in AdCC and scanty in CS; SMA, p63 and Cytokeratine 5/6 (CK5/6) were positive in both. Our results also confirm that AdCC could be true basal-like neoplasia, probably arising from a basal stem line tending to divergent differentiation toward CK5/6/C-kit+, ER/PR-, epithelial basal-like cell type, and toward a myoepitelial-like cell type, with an incomplete SMA/p63+, CD10/HHF35- immunophenotype. By contrast, CS is a reactive, benign proliferation of two well-differentiated cell types: epithelial (ER/PR+, C-kit-) and myoepithelial cells with a complete immunophenotype including CD10/HHF35 positivity. Our study highlights the usefulness of CD10 and HHF35 in the differential diagnosis and helps to understand the histogenesis of the two lesions.
Oral Maxillofac Surg. 2012 Apr 18;: 22527656
Atsushi Kasamatsu, Masashi Shiiba, Dai Nakashima, Ken Shimada, Morihiro Higo, Takashi Ishigami, Shunsaku Ishige, Katsunori Ogawara, Hideki Tanzawa, Katsuhiro Uzawa
Division of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8670, Japan, firstname.lastname@example.org.
BACKGROUND: Myoepithelioma, a generally benign tumor comprised of myoepithelial cells, is an uncommon salivary gland tumor. Among four morphologic variants of myoepithelioma, epithelioid type has not been reported in the oral and maxillofacial region. CASE REPORT: A 61-year-old man first noticed the mass 3 years previously. The oral examination revealed a firm, non-tender, and well-circumscribed mass in the middle of the hard palate. A magnetic resonance imaging scan showed a well-circumscribed mass with low signal intensity (T(1)-weighted image) or increased signal intensity (T(2)-weighted image). DISCUSSION: Immunohistochemically, the tumor cells in the present case reacted to the epithelial (CK HMW and CAM5.2) and the mesenchymal (vimentin) markers. However, myoepithelial markers (S-100 protein, α-smooth muscle actin, glial fibrillary acidic protein, and calponin), except p63, were not expressed in the tumor cells. These results indicated that the epithelial myoepithelioma cells differentiated into epithelial cells rather than myoepithelial cells. We believe that epithelioid myoepithelioma of the palate is a distinctive subtype of myoepithelioma that should be included in the differential diagnosis of tumors of the palate.
Int J Oral Sci. 2012 Apr ;4 (1):50-3 22241374
Department of Dentistry and Oral Surgery, Division of Medicine for Function and Morphology of Sensory Organs, Osaka Medical College, Takatsuki, Japan.
We report a case of carcinoma ex pleomorphic adenoma of a sublingual gland in a 70-year-old man. Under a clinical diagnosis of benign salivary gland tumor, excision of the mass with the sublingual salivary gland in an en bloc fashion via an intraoral approach was performed. Histopathologically, there was a rupture of the fibrous capsule and diffuse cell-rich sheets composed of myoepithelial cells with round nuclei were also seen. Immunohistochemically, the cells that composed of cell rich sheets were positive to smooth muscle actin. Final diagnosis of myoepithelial carcinoma ex pleomorphic adenoma was made.
J Vet Med Sci. 2012 Jan 12;: 22240986
Ayako Shiraki, Yuri Hojo, Takuma Tsuchiya, Liyun Wang, Takumi Ohishi, Kazuhiko Suzuki, Kunitoshi Mitsumori, Makoto Shibutani
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology.
A rare case of complex apocrine carcinoma displaying dominant myoepithelial proliferation developed in the right leg subcutis of a 10-year-old male dog. The major cell population consisted of diffusely proliferating p63-expressing neoplastic cells that were largely myoepithelial in origin co-expressing α-smooth muscle actin. A small portion of the cell population consisted of concomitant basal epithelial cells lacking α-smooth muscle actin expression. The minor population consisted of p63-negative apocrine gland cells that expressed cytokeratin 8. The myoepithelial cell population showed a rather stronger proliferation activity than did the apocrine epithelial population. Thus, this tumor might have been derived from basal epithelial cells characterized by more predominant myoepithelial differentiation than luminal apocrine epithelial differentiation.
The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST)& Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei, China; Department of Oral Histopathology, Faculty of Stomatology, Hainan Medical College, Haikou, Hainan, China.
Epithelial-myoepithelial carcinoma (EMC) is a rare low-grade salivary gland malignancy of presumed intercalated duct origin comprising 1% of all salivary gland tumours. High grade transformation (HGT) in EMC is a recently recognised entity with only a few cases reported in the literature. The authors report an additional case of EMC with HGT involving the submandibular gland. The patient was a 60-year-old woman who requested examination of the rapid growth of a mass in the left submandibular area, which she had first noticed 20 years previously. Histologically, the tumour had two distinct carcinomatous components. One component had features of a low grade EMC. The second component consisted of polygonal cells, arranged in a solid and nested pattern, with marked nuclear pleomorphism, brisk mitotic activity, and frequent necrosis. The Ki-67 labelling index of the EMC component was 9%, and that of the high grade component was 40%. The patient developed multiple pulmonary metastases 15 months after surgery. The aggressive behaviour of EMC with HGT suggests that it is important to recognise this variant of EMC to avoid misdiagnosis and inappropriate treatment.
Oral Oncol. 2012 Feb ;48 (2):102-9 21996542
In vitro influence of the extracellular matrix in myoepithelial cells stimulated by malignant conditioned medium.
Elizabeth F Martinez, Ana Paula Dias Demasi, Marcelo Henrique Napimoga, Victor Elias Arana-Chavez, Albina Altemani, Ney Soares de Araújo, Vera Cavalcanti de Araújo
Department of Oral Pathology, São Leopoldo Mandic Institute and Research Center, Campinas, SP, Brazil. email@example.com
In order to investigate the role of myoepithelial cell and tumor microenvironment in salivary gland neoplasma, we have performed a study towards the effect of different extracellular matrix proteins (basement membrane matrix, type I collagen and fibronectin) on morphology and differentiation of benign myoepithelial cells from pleomorphic adenoma cultured with malignant cell culture medium from squamous cell carcinoma. We have also analyzed the expression of α-smooth muscle actin (α-SMA) and FGF-2 by immunofluorescence and qPCR. Our immunofluorescence results, supported by qPCR analysis, demonstrated that α-SMA and FGF-2 were upregulated in the benign myoepithelial cells from pleomorphic adenoma in all studied conditions on fibronectin substratum. However, the myoepithelial cells on fibronectin substratum did not alter their morphology under malignant conditioned medium stimulation and exhibited a stellate morphology and, occasionally focal adhesions with the substratum. In summary, our data demonstrated that the extracellular matrix exerts an important role in the morphology of the benign myoepithelial cells by the presence of focal adhesions and also inducing increase FGF-2 and α-SMA expression by these cells, especially in the fibronectin substratum.
Kyohei Yasuno, Yoshiichi Takagi, Ryosuke Kobayashi, Tamio Ohmuro, Junichi Kamiie, Hiroeki Sahara, Kinji Shirota
Research Institute of Biosciences, School of Veterinary Medicine, Azabu University, 1-17-71, Fuchinobe, Chuo-ku, Sagamihara, Kanagawa 252-5201, Japan.
The current report describes a complex canine mammary adenoma with a rare histological feature characterized by sebaceous differentiation of tumor cells. A 13-year-old, mixed-breed, intact female dog had mammary tumors on the right mammary chain. Histologically, one of the masses was composed of bilayered ductal structures with luminal epithelial cells together with basaloid or myoepithelial cell components. Within the tumor, there were a number of lobules and nests of large foamy cells associated with basaloid reserve-like cells similar to sebaceous gland. Squamous metaplasia was also seen within the tumor. Immunohistochemical staining indicated that the tumor cells with sebaceous differentiation were positive for cytokeratin (CK)14 and that the associated basaloid reserve-like cells were positive for p63. In contrast, other luminal epithelial tumor cells were positive for CK18 and CK19, but not for CK14 and p63. The myoepithelial cells were positive for α-smooth muscle actin and p63. The expression of p63 in both sebaceous basaloid reserve-like cells and myoepithelial cells, and their structural continuity within the tumor tissue, suggested a common origin of these 2 components.
Faculty of Dentistry, Université de Montréal, Montréal, Canada. firstname.lastname@example.org
Hyalinizing clear cell carcinoma (HCCC) is a low-grade malignancy with infiltrative growth pattern. It affects mainly the minor salivary glands of adult women. The most frequent locations of this tumor are the palate and tongue. HCCC shows a poorly circumscribed, infiltrative, and essentially monomorphic population of clear cells with few mitoses and almost no nuclear or cellular pleomorphism. These cells form trabeculae, cords, islands, and/or nests, circumscribed by variable amounts of hyalinized fibrous bands with foci of myxohyaline stroma. S-100 protein, muscle-specific actin, smooth muscle actin, myosin, and calponin are consistently negative, which strongly indicates the absence of myoepithelial cell differentiation in this tumor. We present a case of HCCC affecting the upper vestibule in a 53-year-old man. The patient was treated by surgery and postoperative radiation and did not show recurrence or distant metastases 3 years after treatment. Discussed also are the clinical and pathologic features of this tumor along with the differential diagnosis and a literature review.
Fernanda Salgueiredo-Giudice, Felipe Fornias-Sperandio, Erika Martins-Pereira, Aluana Maria da Costa dal Vechio, Suzana Cantanhede Orsini Machado de Sousa, Décio dos Santos-Pinto-Junior
Department of Oral Pathology, School of Dentistry, University of São Paulo, São Paulo, Brazil. email@example.com
OBJECTIVE The aim of this study was to demonstrate the immunohistochemical profile of oral inflammatory myofibroblastic tumors (IMTs) along with morphologic analysis. STUDY DESIGN Three cases diagnosed as oral IMTs were selected to compile an immunohistochemical panel constituted by calponin, caldesmon, Bcl-2, desmin, fibronectin, CD68, Ki-67, S100, anaplastic lymphoma kinase (ALK), α-smooth muscle actin, cytokeratins AE1/AE3, muscle-specific actin, CD34, and vimentin. An oral squamous cell carcinoma with a focal area of desmoplastic stroma was used as control for the stained myofibroblastic cells. RESULTS All oral IMTs were positive for calponin, revealing a strong and diffuse expression in the spindle-shaped cells. The lesions were also positive for vimentin (3/3), fibronectin (3/3), α-smooth muscle actin (3/3), and muscle-specific actin (1/3) and negative for h-caldesmon, Bcl-2, desmin, CD68, Ki-67, S100, ALK, cytokeratins AE1/AE3, and CD34. CONCLUSIONS Within the results encountered, the present panel should be of great assistance in the diagnosis of oral IMTs.
Epithelial-myoepithelial carcinoma of the minor salivary glands: immunohistochemical and morphological features.
Anatomia Patologica, Ospedale San Gerardo Via Pergolesi 33, Monza, Italy. firstname.lastname@example.org
AIMS Epithelial-myoepithelial carcinoma (EMC) is a rare malignant salivary gland neoplasm that most commonly occurs in the parotid gland, but can also arise in the minor salivary glands. Three cases are reported of epithelial-myoepithelial carcinoma of the minor salivary glands, with the goal of better defining this entity. PATIENTS AND METHODS All three cases showed a characteristic nodular/multinodular growth pattern and classic biphasic tubular histology. All parts of each tumor were surrounded by a myoepithelial cell rim and there was evidence of invasion. RESULTS Immunohistochemical analysis showed the tumor cells to be weakly positive for S100, cytokeratin (CK) CK5/6, CK7, CKAE-1/AE-3 and strongly positive for epithelial membrane antigen (EMA) and p63; they were focally positive for calponin and acute lymphoblastic leukemia antigen (CD10). The tumor cells were negative for vimentin, alpha-smooth muscle actin (SMA)(except one case), glial fibrillar acid protein (GFAP) and MIB1. The tumors were resected completely with wide margins and no recurrence or metastasis had occurred from 6 to 15 months after surgery. CONCLUSION Three cases of minor salivary gland tumors are described and the differential diagnosis underlined in relation to benign myoepithelioma. The characteristic morphological and immunohistochemical features aided diagnosis of these biphasic tumors.