Salivary Duct Carcinoma - A Highly Aggressive Salivary Gland Tumor with HER-2/neu Oncoprotein Overexpression

Salivary duct carcinoma (SDC) is a highly malignant salivary gland tumor with aggressive clinical behavior, and is characterized by its histological resemblance to invasive ductal carcinoma of the breast. Overexpression and/or amplification of proto-oncogene Her2/neu has been shown to influence both prognosis and treatment of breast cancer. Since salivary duct carcinoma and ductal breast carcinoma share many common characteristics, HER2/neu overexpression might also be important in SDC. However, data on the expression of c-erbB2/HER2/neu in salivary gland tumors are still scarce. Therefore, we have evaluated 15 cases of salivary duct carcinomas (SDC) for HER2/neu overexpression using immunohistochemistry with the HercepTest. Overexpression, identified as strong or moderate membrane immunostaining, was observed in all but one case of SDC in most neoplastic cells. Thus, our study suggests that anti-HER2/neu therapy with Herceptin is beneficial for patients with aggressive salivary duct carcinoma.     

Salivary duct carcinoma--a highly aggressive salivary gland tumor with HER-2/neu oncoprotein overexpression

Salivary duct carcinoma (SDC) is a highly malignant salivary gland tumor with aggressive clinical behavior, and is characterized by its histological resemblance to invasive ductal carcinoma of the breast. Overexpression and/or amplification of proto-oncogene Her2/neu has been shown to influence both prognosis and treatment of breast cancer. Since salivary duct carcinoma and ductal breast carcinoma share many common characteristics, HER2/neu overexpression might also be important in SDC. However, data on the expression of c-erbB2/HER2/neu in salivary gland tumors are still scarce. Therefore, we have evaluated 15 cases of salivary duct carcinomas (SDC) for HER2/neu overexpression using immunohistochemistry with the HercepTest. Overexpression, identified as strong or moderate membrane immunostaining, was observed in all but one case of SDC in most neoplastic cells. Thus, our study suggests that anti-HER2/neu therapy with Herceptin is beneficial for patients with aggressive salivary duct carcinoma.     

Salivary duct carcinoma with neuroendocrine features: report of a case with cytological and immunohistochemical study

We report a salivary duct carcinoma (SDC) of parotid gland in a 75-year-old male. Initially, it was studied by fine-needle aspiration, which disclosed features of malignancy consistent with a high-grade carcinoma. Histologically, the tumor showed typical features of SDC, predominantly with a solid and apocrine pattern. The aggressive behavior of this tumor was documented by facial palsy and the presence of 12 regional lymph node metastases. Immunohistochemical study showed positivity for cytokeratins (AE1/AE3), cytokeratin 7, GCDFP-15, C-erbB-2, Mib-1, topoisomerase II alpha, p53, and androgen receptors. Diffuse positivity with chromogranin-A, synaptophysin, and Grimelius stains was also observed, suggesting endocrine features. Phosphotungstic acid hematoxylin, antimitochondrial antigen, progesterone and estrogen receptors, cytokeratin 20, and S-100 stains were negative. To our knowledge, this is the first case reported of SDC exhibiting neuroendocrine differentiation.     

Primary ductal adenocarcinoma of the lacrimal sac: the first reported case

Primary lacrimal sac tumor is extremely rare, and moreover, glandular tumor is exceptional. Herein, we described the first documented case of primary ductal adenocarcinoma of the lacrimal sac. A 79-year-old Japanese female presented with persistent swelling of her left lower eyelid. Computed tomography demonstrated an irregular-shaped tumor involving the left lacrimal sac, lower eyelid, sinonasal tract, and internal side of the left orbit. Biopsy from the eyelid revealed a poorly differentiated adenocarcinoma. Histopathological study of the resected lacrimal sac tumor revealed an infiltrative neoplastic growth that was composed of cribriform structures with comedonecrosis. The neoplastic cells had relatively rich granular eosinophilic cytoplasm and large round to oval nuclei containing conspicuous nucleoli. The left cervical lymph nodes had metastatic carcinoma. Immunohistochemically, the neoplastic cells were diffusely positive for gross cystic disease fluid protein-15 and androgen receptor. Moreover, mammalian target of rapamycin (mTOR), 4E-BP1, and p4E-BP1 were expressed. According to these results, an ultimate diagnosis of primary ductal adenocarcinoma of the lacrimal sac was made. Only 9 cases of primary lacrimal sac adenocarcinoma have been reported, and this is the first reported case of ductal adenocarcinoma of the lacrimal sac. Ductal adenocarcinoma of the salivary gland shows an aggressive clinical course, and the present case had multiple cervical lymph node metastases. This report is the first to demonstrate that mTOR pathway proteins, which are central proteins involved in carcinogenesis, are activated in ductal adenocarcinoma. Therefore, mTOR inhibitor may be a potential candidate for treatment of this highly aggressive carcinoma.     

Sebaceous carcinoma of the breast

Sebaceous carcinoma (SC) of the breast is a rare malignant tumor and only nine cases, including the present one, have been reported in the English-language literature. The present report describes a case of mammary SC in a 50-year-old Japanese woman. The tumor was gray–white on cut surface and separate from the skin and the nipple. Microscopically, lobules encircled by a fibrous envelope and cords or small cell nests in the stroma were noted. These two types of structures were composed of dark cells and clear foamy cells. The dark cells had large nuclei and amphophilic cytoplasm. The clear foamy cells had numerous lipid vacuoles, confirmed on immunostaining with anti-adipophilin antibody and electron microscopy. In the lobules the gradual transitions from basal dark cells to central clear foamy cells and comedo-like necrosis were observed. The tumor cells were positive on immunohistochemistry for cytokeratins (CAM5.2, AE1/AE3), Her2/neu and androgen receptor but negative for estrogen and progesterone receptors. This is the first case of an androgen receptor-positive mammary SC to be reported, and therefore contributes to the understanding of the clinicopathological features of SC of the breast.     

Sclerosing Mucoepidermoid carcinoma with eosinophilia of the thyroid glands: a case report with clinical manifestation of recurrent neck mass.

Sclerosing mucoepidermoid carcinoma with eosinophilia (SMECE) is a recently recognized malignant neoplasm of the thyroid gland. About 14 cases of SMECE have been reported and this is the first reported case in Korea. A 57-year-old woman presented with right neck mass for 20 years. Total thyroidectomy was performed under the impression of thyroid carcinoma. The resected thyroid gland showed a poorly circumscribed hard mass. Histologically, the tumor consisted of solid nests of large atypical cells with dense fibrous stroma. The tumor cells showed squamoid appearance with abundant eosinophilic cytoplasm. There were also rare mucin-containing cells within the nests. Within the hyalinized stroma, numerous eosinophils were found. The surrounding thyroid parenchyma displayed Hashimoto's thyroiditis. There was metastasis in a regional lymph node. Two years after initial surgery, she underwent a modified radical neck dissection due to recurrent neck mass. After the radiation therapy for eight weeks, laryngectomy and esophagectomy were performed due to a recurrent carcinoma in the esophageal wall. We report an additional case of SMECE, with metastasis to regional lymph nodes and esophagus. The tumor appears to be more aggressive than previously reported and a correct diagnosis can be rendered by just examining the metastatic lesions.     

Metastatic salivary duct carcinoma to the uterus: report of a case diagnosed by cervical smear.

Metastasis to the uterus from extragenital sites is uncommon. We report on a rare case of salivary duct carcinoma (SDC) of the parotid gland with metastasis to the uterus, diagnosed by cervical smear. To the best of our knowledge, this is the first case reported in the literature. A 61-yr-old woman with a prior diagnosis of SDC was admitted to hospital with a fractured left humerus, back pain, and vaginal bleeding. A cervical smear and an endometrial aspiration were performed. The cervical smear showed numerous fragments and many isolated tumor cells in a clean background. The tumor cells were large and had abundant, granular/vacuolated cytoplasm. The nuclei were slightly pleomorphic, with fine chromatin and 1-2 small nucleoli. The malignant cells were morphologically identical to the primary tumor and correlated with the tumor in the endometrial aspiration. A diagnosis of metastatic salivary duct carcinoma was made. Although metastatic SDC to the uterus is rare, this possibility should be considered in the differential diagnosis of a positive cervical smear. This case also illustrates the importance of appropriate clinical history, including the knowledge of a primary tumor which may prevent unnecessary clinical investigations. Diagn. Cytopathol. 1999;21:271-275.     

Aggressive invasive micropapillary salivary duct carcinoma of the parotid gland

The presence of invasive micropapillary component has been reported to be associated with salivary duct carcinoma and poor outcomes. Herein is described a rare case of invasive micropapillary salivary duct carcinoma of the parotid gland in a 60-year-old man. The micropapillary component was approximately 70% of the area of the tumor. Squamous differentiation was focally seen adjacent to the micropapillary component. On immunohistochemistry the ordinary salivary duct carcinoma component was positive for gross cystic disease fluid protein-15 (GCDFP-15), androgen receptor (AR), and HER2/neu, whereas both micropapillary and squamous components were negative for GCDFP-15 and AR. Immunohistochemical staining for D2-40 highlighted the lymph vessel invasion of tumor cells. This patient developed metastases in the lymph nodes of the neck, and also in the liver, lung, and brain. The lymph nodes and liver metastases had both ordinary salivary duct carcinoma and micropapillary components. The patient died of tumor 11 months after the initial surgical operation. The results support that the presence of micropapillary component is associated with more aggressive behavior of salivary duct carcinoma. It is also important for pathologists to recognize that GCDFP-15 and AR expression can be reduced in micropapillary carcinoma in the differential diagnosis of metastatic tumor.     

Androgen receptors are frequently expressed in mammary and extramammary Paget's disease.

Mammary Paget's disease and extramammary Paget's disease are rare intraepithelial neoplasms. Mammary Paget's disease is almost exclusively associated with underlying invasive breast carcinoma or high-grade ductal carcinoma in situ (DCIS G3). Extramammary Paget's disease arises in areas rich in apocrine glands and is suspected to have apocrine gland origin. The aim of the study was to investigate the presence of estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR) and Her2/neu in a large number of cases. We investigated 58 cases of mammary and 23 cases of extramammary Paget's disease. Formalin-fixed and paraffin-embedded tissues were analyzed using antibodies against AR, PR, ER and Her2/neu according to standardized procedures. In mammary Paget's disease, positive immunoreactions for Her2/neu, AR and ER were observed in 56 of 58 (97%), 51 of 58 (88%), and respectively in six of 58 (10%) cases. All cases of mammary Paget's disease were negative for PR and showed a coexpression of Her2/neu and AR in 51 out of 58 cases (88%). In extramammary Paget's disease, positive immunoreactions for AR, Her2/neu and ER were observed in 18 of 23 (78%), 12 of 23 (52%), and respectively in 1 of 23 (4%) cases. All cases of extramammary Paget's disease were negative for PR and showed a coexpression of AR and Her2/neu in 12 out of 23 cases (52%). In contrast to ER and PR, AR and Her2/neu are commonly expressed in mammary and extramammary Paget's disease. The knowledge about frequent expression of AR in Paget's disease could lead to the development of a new adjuvant therapy, particularly in patients with recurrent disease.     

Ultrastructural and Immunohistochemical Study of Salivary Duct Carcinoma of the Parotid Gland

A case of salivary duct carcinoma of the parotid gland found in an 81-year-old man was studied by light microscopy, immunohistochemistry, and electron microscopy. Histologically, the tumor was composed of elongated cords of cells and ductal structure with desmoplastic stromal reaction. Tumor cell nests sometimes showed central comedonecrosis. Immuno-histochemically, the tumor cells were positive for cytokeratin and epithelial membrane antigen, and they were negative for S-100 protein and muscle-specific actin. Electromicroscopi-cally, two cell types were identified. The first cell type showed electron-lucent cytoplasm with scant organelles. The second type cell contained numerous mitochondria. Neither acinar nor myoepithelial cell differentiation was observed. These findings suggest that salivary duct carcinoma originates from the interlobular or excretory ducts.     

Prognostic significance of micropapillary pattern in pure mucinous carcinoma of the breast

Breast carcinoma with micropapillary architecture is associated with aggressive behavior. Similar micropapillary pattern in pure mucinous carcinoma has been noticed and has been shown to convey poor prognosis. In this study 17 cases of pure mucinous carcinoma of the breast seen during a 10-year period have been reviewed, with special reference to micropapillary pattern. Diffuse micropapillary pattern was seen in 6 of 17 cases of mucinous carcinoma of the breast and demonstrated reverse polarity immunostaining pattern with "Epithelial Membrane Antigen." In all cases, the tumor cells showed grade I morphology, and no lymph node metastases were noticed. All the tumors except 1 expressed strong estrogen and progesterone receptor expression, however, all the cases were negative for Her-2/neu expression. In this present study, mucinous carcinomas with micropapillary pattern showed a low nuclear grade, higher incidence of hormone receptor positivity, and lower incidence of Her-2/neu similar to mucinous carcinomas without micropapillary pattern, thus explaining their indolent behavior.     

Mucin-rich salivary duct carcinoma with signet-ring cell feature ex pleomorphic adenoma of the submandibular gland: a case report of an unusual histology with immunohistochemical analysis and review of the literature

Salivary duct carcinoma (SDC) is a highly aggressive salivary gland carcinoma, and the mucin-rich variant of SDC (mSDC) is extremely rare. We report herein one case of salivary mSDC, showing predominantly signet-ring cell features. The patient was an 84-year-old Japanese woman, who noticed swelling in the left submandibular region. The tumor consisted of two components: one was of mSDC, which contained numerous signet-ring cells in large mucinous lakes, whereas the other was of preexisting pleomorphic adenoma (PA), which showed a hyalinized nodule. mSDC was markedly positive for mucin staining. Signetring cells in the mSDC component were immunopositive for androgen receptor, gross cystic disease fluid protein-15, MUC1, MUC2, MUC5AC, MUC5B, and MUC6, but negative for Her-2 and myoepithelial markers. This case was diagnosed as mSDC with the signet-ring cell feature ex PA. We discuss herein the significance of the signet-ring cell feature in mSDC and the mucin pattern of mSDC.     

Sarcomatoid variant of salivary duct carcinoma: clinicopathologic and immunohistochemical study of eight cases with review of the literature

Salivary duct carcinoma (SDC) is an uncommon, high-grade tumor. We present 8 cases of sarcomatoid SDC, which has been defined recently as a rare variant of SDC. The 8 patients (5 men, 3 women) had a mean age of 63.6 years. Histologically, all tumors were characterized by a biphasic neoplasm composed of both SDC and sarcomatoid elements. In 3 cases, sarcomatoid components showed osteosarcomatous heterologous differentiation. A residual pleomorphic adenoma was detected in 5 tumors. The sarcomatoid component showed focal immunoreactivity for cytokeratin in 4 cases and epithelial membrane antigen in all 8 cases. Diffuse p53 immunostaining was detected in 3 cases, and it was coexpressed in both components. Our observations support the histogenetic theory of a common origin of the carcinomatous and sarcomatoid populations. Of the 13 patients, including our 8, reported to have sarcomatoid SDC arising in a major salivary gland and for whom long-term follow-up data were available, 7 have died of disease (mean survival, 15.6 months). These results indicate that sarcomatoid SDC is a highly aggressive tumor, similar to conventional SDC.     

Oncocytic lipoadenoma of the parotid gland: Cytological findings and differential diagnosis on fine‐needle aspiration

Oncocytic lipoadenoma is a rare benign neoplastic lesion of salivary gland. To the best of our knowledge, the detailed cytomorphological findings were described only in two cases. We are reporting a 56‐year‐old woman who presented with 1‐year history of right parotid gland mass. Cytologic examination revealed tight clusters of bland looking oncocytic ductal cells with few aggregates of mature adipose tissue in a lipoid background and a benign oncocytic tumor of parotid gland was rendered. Histologically, a tumor with islands of oncocytic epithelial cells admixed with abundant mature adipose tissue was identified. Oncocytic lipoadenoma despite its rarity should be considered in the differential diagnosis of salivary gland fine‐needle aspirations containing oncocytes especially those which are accompanied by mature adipose tissue and lipoid background. Diagn. Cytopathol. 2015;43:72–74. © 2014 Wiley Periodicals, Inc.     

Metaplastic variant of invasive micropapillary breast carcinoma: a unique triple negative phenotype

Invasive micropapillary carcinomas (IMC) and metaplastic breast carcinoma (MBC) have different clinicopathologic features. This study reports an unusual case of multifocal grade III IMC associated with MBC component in a 35-year-old woman. MBC was vimentin positive, pancytokeratin negative, and showed focal p63 positivity. Immunostains for estrogen and progesterone receptor, and fluorescence in situ hybridization for Her2/neu amplification were negative. All the left axillary lymph nodes dissected were positive for metastatic carcinoma with ductal and IMC patterns, but without metaplastic component. Postmastectomy computed tomography and magnetic resonance imaging scans showed metastases to lungs, liver, brain, and vertebrae. The biologic behavior of tumor was in accordance with histology, so that the nodal and distant metastases were testament to the underlying inherently aggressive IMC, whereas large tumor size and triple negativity reflected the features of MBC. To the best of the authors' knowledge, this is the first report of a metaplastic variant of invasive micropapillary breast carcinoma with triple negative phenotype.     

Spinal adrenal cortical adenoma with oncocytic features: report of the first intramedullary case and review of the literature

Ectopic adrenal cortical neoplasms are extremely rare, and only a few have involved the CNS. We report the first case of an intramedullary oncocytic adrenal cortical neoplasm of the spinal cord with immunohistochemical (IMHC) confirmation. A 27-year-old man presented with progressive lower extremity weakness, spastic paraparesis, decreased reflexes, and hypoesthesia below T10. A spinal myelogram showed cauda equina blockade and obliteration of sacral nerve roots. This prompted emergent surgical intervention. A well-circumscribed, approximately 3 x 2 cm, light brown to tan, intramedullary tumor was identified at the level of the conus medullaris. Histologically, the tumor showed sheets and nests of plump, cytologically bland polygonal cells with abundant eosinophilic cytoplasm. A single mitosis, but no necrosis, was identified. By IMHC, the cells were positive for inhibin, melan-A, and synaptophysin, and negative for GFAP, EMA, cytokeratins, S-100, HMB-45, and chromogranin. Electron microscopy study performed from paraffin-embedded tissues demonstrated abundant mitochondria, and lipid vacuoles. This case confirms the occurrence of adrenal cortical neoplasms in the CNS and is the first report of an intradural, intramedullary adrenal cortical adenoma of the spinal cord, and the first to occur in a male. This tumor should be considered in the differential diagnosis of tumors of the CNS.     

Histiocytoid carcinoma of the male breast

Histiocytoid carcinoma of the breast is a rare tumor with approximately 30 cases reported, all occurring in female patients. We report the first case of histiocytoid breast carcinoma in a male patient. A 68-year-old man presented with a 2.5-cm breast mass. Microscopic examination of the needle core biopsy revealed a diffuse (lobular type) infiltration of tumor cells as angulated clusters, linear arrangements, small nests, and individual cells; there was no duct formation. The nuclei were round-oval and hyperchromatic with inconspicuous nucleoli and finely dispersed chromatin. The cytoplasm was abundant, was amphophilic, and ranged from granular to vacuolated. A subset of tumor cells contained periodic acid Schiff-positive cytoplasmic material, which was largely but incompletely removed by diastase treatment. There was minimal nuclear pleomorphism, and mitotic figures were inconspicuous. The intervening stroma was densely fibrotic, and the tumor infiltrated among tightly packed collagen bundles. Immunohistochemistry was positive for estrogen receptor, progesterone receptor, androgen receptor, vimentin, epithelial membrane antigen, and pan-cytokeratin. The tumor was negative for CK7, CAM5.2, 34BE12, AE1/AE3, GCDFP-15 (BRST-2), E-cadherin, and CD68. The mastectomy resection demonstrated similar histologic findings. Sentinel lymph node biopsy was negative. The morphology of this tumor is similar to that described for histiocytoid carcinoma of the female breast, a rare entity. Such tumors are felt to be variants of lobular carcinomas, which is supported by diffuse infiltrative growth, loss of E-cadherin expression, and strong ER positivity. We believe our case to be the first reported example of histiocytoid carcinoma in a male breast.     

Amplification and overexpression of HER-2/neu in parotid gland salivary duct carcinoma. Immunohistochemical study and fluorescence in situ hybridization

Salivary duct carcinoma (SDC) is highly malignant salivary gland tumour with aggressive clinical behaviour, characterised by its histological resemblance to invasive ductal carcinoma of the breast. Amplification of gene HER-2/neu and overexpression of its gene product have been shown to have both prognostic and treatment implications in breast cancer. The reports concerning the expression of c-erbB2/HER-2/neu in salivary gland tumours are few and controversial. Thus, eleven cases of SDC were evaluated for HER-2/neu status using immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). To the best of our knowledge, this is the first molecular genetic analysis of SDCs using FISH. HER-2/neu overexpression, identified as strong membrane staining, was observed in all but one case of SDC in majority of neoplastic cells while only four tumours, of nine cases analysed, revealed HER-2/neu gene amplification by means of FISH analysis. SDCs were associated with poor clinical outcome, 6 patients (55%) died of disseminated carcinoma within 4 to 44 months after therapy. There was no difference in outcome of patients with IHC positive-nonamplified and IHC positive-amplified tumours.     

Gastric small cell carcinoma with squamous and neuroendocrine differentiation.

A rare gastric carcinoma containing diverse components, that is, neuroendocrine (small cell carcinoma), squamous and gland-like elements in an 82 yr old woman is described. Radiologic examination revealed a large ulcerated tumor, and a Borrmann type II tumor, 6.5 x 5 cm, was found in the resected stomach. Histologically, the tumor was mainly composed of small cells with hyperchromatic nuclei and scant cytoplasm. Argyrophilic granules were seen in these cells. There were also scattered foci of large cells with features of squamous cells, and many intermediate cells with oncocytic cytoplasm. The small cancer cells were positive for chromogranin A and neuron specific enolase. Squamous cell nests were positive for high molecular cytokeratin (CK), and intermediate cells were positive for low molecular CK. Electron microscopic examination revealed secretory granules in the small cells and tonofilaments in the squamous cells. This tumor might have originated from the pluripotential stem cell in the gastric epithelium.     

Low-grade salivary duct carcinoma of the parotid gland: report of a case with immunohistochemical analysis

Salivary duct carcinoma (SDC) is a highly aggressive malignancy of the salivary glands. However, one type of SDC, which shows minimal invasion and better prognosis, is known as low-grade SDC (LG-SDC). This report presents an additional case of LG-SDC of the parotid gland. The patient was a 38-year-old Japanese woman who noticed painless swelling of the left parotid region. Grossly, the cut surface of the tumor was cystic. Microscopically, the tumor showed a multicystic pattern, which was lined by eosinophilic to clear atypical cells with cribriform or Roman bridge patterns. An immunohistochemical examination revealed the tumor was positive for cytokeratin (CK) 7 and epithelial membrane antigen, partially positive for androgen receptor and gross cystic disease fluid protein-15, and diffusely positive for Her-2/Neu, progesterone, and estrogen receptors. The cancer cells showed focal immunopositivity for S-100 protein. Immunostaining for p63, CK14, and calponin showed an in situ pattern in most areas of this tumor, whereas the tumor showed minimal invasion. The cancer cells were diffusely positive for MUC1 and MUC6 and focally positive for MUC2 and MUC4. Finally, the tumor was diagnosed to be LG-SDC. The differential diagnosis and the mucin pattern were evaluated.