Microsecretory Adenocarcinoma: A Novel Salivary Gland Tumor Characterized by a Recurrent MEF2C-SS18 Fusion.

Salivary gland adenocarcinoma not otherwise specified (NOS) is a heterogenous group, likely containing distinct tumors not yet characterized. A growing number of low to intermediate-grade salivary carcinomas are now known to harbor tumor-specific gene fusions. On occasion, identifying a novel fusion allows for recognition of a new salivary tumor type, in addition to representing a potential diagnostic tool. We sought to characterize a distinctive salivary gland adenocarcinoma that would previously have been regarded as adenocarcinoma NOS. On the basis of the recognition of 5 morphologically identical, distinct low-grade salivary adenocarcinomas, we used targeted RNA sequencing (RNA-Seq) to determine whether these could be differentiated from other fusion-associated salivary gland tumors. RNA-Seq was performed on all 5 low-intermediate grade adenocarcinomas NOS with near-identical histologic appearances, as well as 23 low-intermediate grade control adenocarcinoma NOS cases that did not resemble the index cases. All 5 index cases harbored a novel MEF2C-SS18 gene fusion, which was independently confirmed by reverse transcriptase-polymerase chain reaction. The MEF2C-SS18-positive cases arose in the oral cavity (4/5) and parotid gland (1/5) of 3 women and 2 men ranging from 21 to 80 years (mean: 46) and shared near-identical histologic features: intercalated duct-like cells with eosinophilic to clear cytoplasm and small, uniform oval nuclei, infiltrative microcysts and cords, abundant intraluminal secretions, and cellular fibromyxoid stroma. Mitotic rates were low; necrosis was absent. All MEF2C-SS18-positive tumors were positive for S100 and p63 and negative for p40, smooth muscle actin, calponin, and mammaglobin. One of the 23 control cases, a parotid tumor, was found to contain a SS18-ZBTB7A gene fusion; it demonstrated similar, but not identical histologic and immunophenotypic features compared with the MEF2C-SS18 cases. The remaining control cases were negative for SS18 and MEF2C rearrangements. A novel MEF2C-SS18 gene fusion and unique histologic and immunophenotypic features characterize a heretofore undefined low-grade salivary adenocarcinoma for which we propose the term "microsecretory adenocarcinoma." RNA-Seq helped establish this entity as a distinct tumor type, and identified one possibly related case with a different SS18-related fusion. The recognition of microsecretory adenocarcinoma and its separation from other adenocarcinomas NOS will facilitate a more complete understanding of the clinical and pathologic characteristics of this previously unrecognized neoplasm.

CD34-positive dendritic cells disappear from scars but are increased in pericicatricial tissue.

CD34-positive stromal cells (CD34SC) are distributed throughout the body, including the dermis. They are thought to play a role in maturation and proliferation of adjacent mesenchymal and epithelial stem cells and in immune responses. To investigate the role of such cells in wound healing after excision of cutaneous lesions, we examined the distribution and quantity of CD34SC in scars from the sites of removal of malignant skin tumors and from reconstructive surgery, as well as in samples of normal skin. In normal skin, CD34 staining was confined to dendritic cells in the dermis, endothelial cells, perifollicular cells and eccrine glands. In cutaneous scars, the cicatricial tissue was totally devoid of CD34SC. However, the dermis adjacent to scar showed increased numbers of CD34SC as compared with normal skin [41.5 cells/mm(2) vs. 24.5 cells/mm(2) (p < 0.001)]. We conclude that CD34SC disappears from scars but are induced to proliferate in pericicatricial tissue. The cells in question may play a role in remodeling of scarred skin. One should be aware that augmented labeling for CD34SC around scars is common; it should not be interpreted as evidence for the persistence or recurrence of tumors that may also express CD34.

Immunoglobulin A pemphigus involving the perianal skin and oral mucosa: an unusual presentation.

Immunoglobulin A (IgA) pemphigus is a rare autoimmune blistering disease characterized by epidermal acantholysis and neutrophilic infiltrates, as well as intraepidermal IgA deposits. We report an unusual case of IgA pemphigus involving anal/ perianal skin and oral mucosa that demonstrated a successful response to dapsone treatment.

E-cadherin status in breast cancer correlates with histologic type but does not correlate with established prognostic parameters.

Our objective was to assess the loss of E-cadherin (EC) as a diagnostic marker or a predictor of prognosis. We stained 276 breast carcinomas with monoclonal antibodies to EC (invasive lobular carcinomas [ILC] and variants, 59; invasive ductal carcinoma and ductal special types [IDC], 204; tubulolobular carcinoma [TLC], 4; and invasive carcinoma [IC], uncertain whether lobular or ductal type, 9). The results were as follows: EC+IDCs, 99.5%; EC-ILCs, 90%; EC+ILCs, 10%; EC+pleomorphic ILCs, 20%; EC-ICs, 44%. All 4 TLCs showed positive tubules while cords were negative. Statistically a correlation of EC loss with a positive diagnosis of ILC was found but there was no correlation with any prognostic tumor variables. A negative EC stain confirms the diagnosis of ILC (specificity, 97.7%; negative predictive value, 96.8%; sensitivity, 88.1%; positive predictive value, 91.2%). EC is helpful in classifying cases with indeterminate histologic features. EC loss is uncommon in nonlobular carcinomas with no correlation to currently established prognostic variables.

Solitary fibrous tumors of the skin: a clinicopathologic study of 10 cases and review of the literature.

Solitary fibrous tumor (SFT) is a relatively uncommon neoplasm that most commonly arises in the pleura. However, SFT is now known to affect various other anatomic sites as well, including rare examples in the skin, where the histologic features of this lesion may create diagnostic confusion with a variety of other spindle-cell tumors. In order to further the characterization of cutaneous SFT, all available cases of that entity were retrieved from the authors' institutional files. Immunohistochemical analysis for CD-34, CD-99, vimentin, bcl-2, factor XIIIa, S100 protein, smooth muscle actin, pankeratin, epithelial membrane antigen (EMA) and desmin was performed on those neoplasms and the corresponding clinical information was obtained whenever possible. There were eight men and two women in the study group, with a median age of 43 years. Sites of involvement included the trunk (two cases), cheek (two), scalp (one), forehead (one), lip (one), temple (one), heel (one) and toe (one). All patients were treated with local excision; only one lesion recurred locally, but it required multiple re-excisions. All of the neoplasms were composed of bland spindle cells with a variably fibrous but focally hyalinized collagenous stroma. A variety of case-specific growth patterns were observed. Mitoses were generally rare, ranging from 0 to 3 per 10 x400 microscopic fields. Immunostains showed reactivity for vimentin in all SFTs, CD-34 in 8 of 10 cases, CD-99 and bcl-2 in 4 of 10 (each) and smooth-muscle actin in 3 of 10 cases. None of the lesions was labeled for factor XIIIa, keratin, EMA, desmin or S100 protein. SFT of the skin appears to be a 'borderline' neoplasm that only uncommonly recurs. Immunoreactivity for CD-34, - especially together with bcl-2 or CD-99, or both - is helpful in identifying this tumor.

The diagnostic utility of p63, CK5/6, CK 7, and CK 20 in distinguishing primary cutaneous adnexal neoplasms from metastatic carcinomas.

BACKGROUND: Distinguishing primary cutaneous adnexal neoplasms (PCANs) from metastatic carcinomas (MCs) can be difficult. We study the utility of p63, CK 5/6, CK 7, and 20 expression in PCAN vs. MC. METHODS: Twenty-one PCAN with sweat gland differentiation (six benign, 15 malignant), one sebaceous carcinoma, and 15 MC (14 adenocarcinomas, one urothelial carcinoma) to skin were retrieved from the pathology files. Immunostains for p63, CK 5/6, CK 7, and CK 20 were performed and graded as follows: 1, <10; 2, 11-50; and 3 >50% of tumor cells stained. RESULTS: Twenty of 22 PCAN expressed p63 and CK 5/6. Four of 15 and two of 15 MC were positive for CK 5/6 and p63, respectively. Thirteen of 22 PCAN and 13 of 15 MC were positive for CK 7, respectively. All PCAN were negative for CK 20, two of 15 MC were positive. The sensitivity and specificity for the diagnosis of PCAN were 91 and 73% for CK 5/6, 91 and 100% for p63, and 60 and 13% for CK 7, respectively. CONCLUSIONS: For distinguishing PCAN from MC: (1) positivity for p63 and CK 5/6 are relatively specific and sensitive for PCAN, (2) CK 7 and 20 are neither sensitive nor specific, and (3) CK 7 positivity in PCAN was focal with a specific pattern in contrast to the diffuse positivity for MC.

Primary cutaneous mucinous carcinoma: presence of myoepithelial cells as a clue to the cutaneous origin.

BACKGROUND: Primary cutaneous mucinous carcinoma (PCMC) is a rare malignancy with probable apocrine differentiation. It is important to differentiate it from metastatic mucinous carcinoma (MMC), especially from the breast. The histologic and immunohistochemical features overlap between PCMC and breast mucinous carcinomas. In this study, we introduce the presence of myoepithelial component in PCMC as a new morphologic parameter to distinguish it from MMC from either breast or sites elsewhere in the body. MATERIALS AND METHODS: We studied 7 cases of PCMC. The possible in situ component in the tumor was assessed by the presence of a peripheral myoepithelial cell layer. Myoepithelial cell differentiation was confirmed with immunohistochemical stains for p63, CK 5/6, calponin, smooth muscle actin (SMA), HHF-35, and CD10. Estrogen and progesterone receptor (ER/PR), gross cystic disease fluid protein (GCDFP 15), CK7, CK20, and S-100 immunostains were also performed. RESULTS: Histologically, multiple small monomorphic epithelial islands floating in multilocular pools of mucin characterized the tumor. Focally, epithelial islands were bordered by dermal connective tissue at the periphery of mucin pools. Secretory snouts were apparent in all cases providing evidence for apocrine differentiation. In 5 of the 7 cases, an in situ component was identified as epithelial islands being bounded by a myoepithelial layer, which was highlighted by p63, CK 5/6, calponin, SMA, and HHF-35. ER/PR and CK7 were positive in all the cases. GCDFP-15 and CD10 were focally positive in the tumor cells and myoepithelial cells, respectively. All 7 cases were negative for S-100 and CK 20. CONCLUSION: We conclude that an in situ component is frequently present in PCMC (5/7) and may help in distinguishing this entity from MMC, especially of breast origin. Furthermore, it may provide insight into the pathogenetic mechanism of mucinous carcinoma evolving from in situ carcinoma with luminal mucinous distention to cellular tumor with a little surrounding mucin.