Hillary Elwood

Neural crest transcription factor Sox10 is preferentially expressed in triple-negative and metaplastic breast carcinomas

The transcription factor Sox10 mediates the differentiation of neural crest-derived cells, and Sox10 labeling by immunohistochemistry (IHC) is used clinically primarily to support the diagnosis of melanoma. Sox10 expression by IHC has been previously documented in benign breast myoepithelial cells but not in breast carcinomas. Here, we report the first systematic study of Sox10 expression in invasive ductal carcinomas subclassified by IHC-defined molecular subtype (100 cases), as well as in 24 cases of ductal carcinoma in situ and 44 mammary fibroepithelial neoplasms. Tissue microarrays containing 168 primary breast tumors were subjected to IHC for Sox10. The extent of nuclear Sox10 labeling was scored by percentage labeling as follows: 0 (0%), 1+ (1%-25%), 2+ (25%-50%), 3+ (50%-75%), and 4+ (>75%). Overall, 40 (40%) of 100 invasive breast carcinomas demonstrated Sox10 immunoreactivity, which was seen primarily in the basal-like, unclassified triple-negative, and metaplastic carcinomas. Sox10 labeling was seen in 66% (38/58) of the basal-like, unclassified triple-negative, and metaplastic carcinomas as compared with 5% (2/42) of the luminal A, luminal B, and Her-2 carcinomas (P < .00001). Sox10 labeling was seen in 1 (4%) of 24 cases of ductal carcinoma in situ, which was negative for estrogen receptor/progesterone receptor. No labeling was seen in the stromal component of phyllodes tumors or fibroadenomas. These findings show that breast carcinoma must be considered in the differential diagnosis of melanoma for an S100-positive, Sox10-positive metastatic malignant neoplasm. Sox10 expression in the basal-like, unclassified triple-negative, and metaplastic carcinomas types supports the concept that these neoplasms show myoepithelial differentiation.

The immune microenvironment of breast ductal carcinoma in situ

The host immune response has a key role in breast cancer progression and response to therapy. However, relative to primary invasive breast cancers, the immune milieu of breast ductal carcinoma in situ (DCIS) is less understood. Here, we profile tumor infiltrating lymphocytes and expression of the immune checkpoint ligand programmed death ligand 1 (PD-L1) in 27 cases of DCIS with known estrogen receptor (ER), progesterone receptor, and human epidermal growth factor 2 (HER-2) expression using tissue microarrays. Twenty-four cases were pure DCIS and three had associated invasive ductal carcinoma. Tumors were stained by immunohistochemistry for PD-L1, as well as the lymphocyte markers CD3, CD4, CD8, FoxP3, and CD20. The expression of PD-L1 by DCIS carcinoma cells and tumor infiltrating lymphocytes was determined, and the average tumor infiltrating lymphocytes per high power field were manually scored. None of the DCIS cells expressed PD-L1, but 81% of DCIS lesions contained PD-L1+ tumor infiltrating lymphocytes. DCIS with moderate-diffuse tumor infiltrating lymphocytes was more likely to have PD-L1+ tumor infiltrating lymphocytes (P=0.004). Tumor infiltrating lymphocytes with high levels of PD-L1 expression (>50% cells) were seen only in triple-negative DCIS (P=0.0008), and PD-L1−tumor infiltrating lymphocytes were seen only in ER+/HER-2−DCIS (P=0.12). The presence of PD-L1+ tumor infiltrating lymphocytes was associated with a younger mean patient age (P=0.01). Further characterization of the DCIS immune microenvironment may identify useful targets for immune-based therapy and breast cancer prevention.

Immunohistochemical analysis of SMARCB1/INI-1 expression in collecting duct carcinoma.

OBJECTIVES Collecting duct carcinoma (CDC) is a rare and aggressive renal tumor with a tendency to involve the renal sinus. CDC displays variable morphologic features that can overlap with those of renal medullary carcinoma. The loss of SMARCB1/INI1 tumor suppressor gene, initially found in pediatric malignant rhabdoid tumors of the central nervous system, kidneys, and soft tissues, was also recently described in renal medullary carcinoma. The current immunohistochemical study assessed SMARCB1/INI1 expression in a series of CDCs. METHODS A total of 20 archival cases of CDC were used to construct a tissue microarray. Each tumor was spotted 3-7 times; benign tissue from the same specimen was also included when available. The immunoexpression of SMARCB1/INI1 was evaluated using BAF47, a monoclonal mouse antibody directed against the SMARCB1/INI1 gene product. Nuclear staining was considered as indicative of SMARCB1/INI1 expression. RESULTS The complete loss of SMARCB1/INI1 expression was observed in 3 of 20 cases of CDC. Another 3 cases revealed focal and weak intensity staining. The remaining tumors showed multifocal or diffuse SMARCB1/INI1 expression with variable staining intensity. No significant differences were found in the clinicopathologic and outcome features regarding SMARCB1/INI1 status. CONCLUSIONS The complete loss of SMARCB1/INI1 immunoexpression was found in 15% of CDC. No differences were found between the SMARCB1/INI1 positive and negative cases regarding the clinicopathologic and outcome features. Our results suggest that some CDC cases might be associated with genetic alterations involving the SMARCB1/INI1 gene. In addition, SMARCB1/INI1 immunoexpression seems to be of limited value in the differential diagnosis of CDC versus renal medullary carcinoma, although these results require additional validation.

Clinicopathologic features of ductal carcinoma in situ in young women with an emphasis on molecular subtype.

Young women with ductal carcinoma in situ treated by breast-conserving therapy have a higher recurrence rate than do older women, and a younger age at diagnosis is associated with worse overall survival after recurrence. This study explores the clinical, pathologic, and immunohistochemical characteristics of ductal carcinoma in situ lesions diagnosed in women 40 years and younger with a focus on molecular subtypes to elucidate features that may contribute to the purported worse outcome for this patient population. Forty-one patients diagnosed with ductal carcinoma in situ at age 40 years and younger were identified over a 10-year period; 31 cases were used to construct tissue microarrays. The microarrays were labeled with antibodies to estrogen receptor, progesterone receptor, HER2, Ki-67, CK5/6, epidermal growth factor receptor, and p53 and subsequently classified as luminal A, luminal B, HER2, basal-like, or unclassifiable triple negative. All patients had high-grade (73.2%) or intermediate-grade (26.8%) ductal carcinoma in situ. The molecular subtype breakdown was 61.3% luminal A, 22.6% luminal B, 13% HER2, and 3.1% unclassifiable triple negative. The mean Ki-67 by subtype was 4.2%, 14%, 9.5%, and 50%, respectively. Mastectomy was performed in 33 patients (80%). Eight patients (20%) underwent excisional biopsy without subsequent mastectomy. In addition to a predominance of high-grade lesions, young patients had a high proportion of luminal B subtype, which may contribute to an increased rate of local recurrence in this population. A larger series is necessary to confirm the impact that the molecular subtypes of ductal carcinoma in situ in younger patients might have on outcome.

Nuclear factor XIIIa staining (clone AC-1A1 mouse monoclonal) is a highly sensitive marker of sebaceous differentiation in normal and neoplastic sebocytes.

Sebaceous proliferations are common and may be confused with other cutaneous neoplasms. Few useful or specific immunohistochemical markers for sebaceous differentiation are available. We incidentally observed strong factor XIIIa (Ventana clone AC‐1A1 on Ventana Benchmark Ultra stainer) nuclear staining in normal sebaceous glands and hypothesized that this might be a useful marker in sebaceous proliferations.

Superficial fibrin thrombi … and other findings: a review of the histopathology of human scabietic infections.

Cutaneous infection with the mite Sarcoptes scabiei var. hominis is associated with epidermal and dermal changes. After noting superficial fibrin thrombi in two biopsies with scabies mites, we comprehensively reviewed the histopathologic findings in scabietic infections to determine the frequency of this finding.

A case of a giant sarcomatoid basal cell carcinoma with heterologous osteosarcomatous elements.

To the Editor, Giant basal cell carcinomas, defined as tumors greater than 5.0 cm, are rare.1 Also rare are basal cell carcinomas with heterologous osteosarcomatous elements, there being only 13 cases previously described in the literature.2– 4 Herein, we describe a recent case that was both giant (9.4 cm in greatest dimension) and that showed osteosarcomatous differentiation; additionally, this case occurred on the skin of a very elderly patient (over 90 years of age). This is the largest example of, and the oldest patient with, this rare and interesting tumor. An elderly woman was evaluated by a dermatologist for a nodule on the extensor aspect of her left arm. She was unable to provide information as to how long the tumor had been present. Examination revealed a 9.4 × 5 cm, firm, exophytic tumor with superficial ulceration. The mass was narrowly excised and sent for histopathologic evaluation. Microscopic sections showed a multinodular basaloid neoplasm with characteristic features of a basal cell carcinoma including peripheral palisading, peritumoral clefting, stromal mucin and apoptotic cells. Deep to, and merging with, the typical basal cell carcinoma were sheets of pleomorphic spindled cells (Figs. 1 and 2). Intimately associated with this sarcomatoid component was ‘lace-like’ osteoid deposition, a feature diagnostic of osteosarcoma (Fig. 3A,B). Portions of the tumor showed an elevated mitotic index. These findings were interpreted as sarcomatoid basal cell carcinoma with heterologous osteosarcomatous elements. Basal cell carcinoma, the most common cutaneous malignancy, only rarely shows sarcomatoid morphology. Although areas resembling undifferentiated pleomorphic sarcoma (previously, malignant fibrous histiocytoma), chondrosarcoma, leiomyosarcoma and Fig. 1. Basaloid tumor cells with connection to the overlying epidermis merging into areas with sarcomatous stroma and prominent osteoid deposition (×4).

Dermal and Subcutaneous Plexiform Soft Tissue Neoplasms

This article presents an overview of soft tissue tumors that have a plexiform histomorphology. The more commonly encountered entities, including plexiform fibrohistiocytic tumor, cellular neurothekeoma, dermal nerve sheath myxoma, plexiform schwannoma, and plexiform neurofibroma, are discussed in detail, and other tumors are noted. Information on clinical features, microscopic findings, ancillary studies, differential diagnosis, and prognosis is provided for each entity.

Characterization of dermatopathology fellowship applicants: a 5-year single institution experience.

Although much data have been documented on the characteristics of medical school applicants for dermatology and pathology residency programs in the United States and select medical and surgical fellowship applicants through the National Residency Matching Program, little is known about the dermatopathology applicant demographics.

Hard to Swallow: A Rare Cause.

A 66-year-old woman underwent open-access upper endoscopy indicated for a two-month history of odynophagia and dysphagia for solids and liquids, described as difficulty in initiating a swallow followed by the subsequent sensation of food and liquids ‘‘holding up’’ in her mid-chest. Past medical history included type 2 diabetes mellitus, hypertension, and dyslipidemia; medications consisted of aspirin, rosuvastatin, losartan, hydrochlorothiazide, omeprazole, glipizide, metformin, oral potassium chloride, thyroid hormone, and insulin glargine. There had been no recent changes in medications or dosages. A focused physical examination prior to the endoscopy was unremarkable. Laboratory evaluation includes a complete blood cell count and basic metabolic panel that also revealed no abnormality. Endoscopy revealed an area of healing confluent ulceration extending over several centimeters in the hypopharynx (Fig. 1a). There was also severe, circumferential, erosive esophagitis that extended 5 cm proximally from the gastroesophageal junction (Fig. 1b). Biopsies of the distal esophagus were taken due to the possibility of a viral etiology of the severe ulceration. Following one of the esophageal biopsies, a prominent mucosal defect concerning for a superficial tear was noted for which an endoscopic hemoclip was deployed; no other complications of endoscopy occurred. In addition to standard anti-reflux measures, the patient was prescribed omeprazole. The esophageal biopsies were reported as showing a focally ulcerated fragment of squamous mucosa with associated fibropurulent material, consisting ofmixed inflammatory cells. No nuclear or cytoplasmic inclusions were reported. After endoscopy, her primary care provider prescribed topical treatments for suspected aphthous hypopharyngeal ulceration. Four weeks after endoscopy, she complained of worsening oral pain without improvement of her initial symptoms of odynophagia and dysphagia. An oropharyngeal examination during a clinic visit revealed exudative hypopharyngeal erythema with cracking and ulceration of the buccal mucosa, consistent with the appearance of severe aphthous stomatitis. In view of these findings, buccal biopsies were obtained, which were reported as suprabasal epidermal acantholysis compatible with pemphigus vulgaris (Fig. 2a). Review of the first esophageal biopsy identified a single mucosal fragment with similar suprabasal acantholysis in the buccal specimen, confirming the diagnosis of esophageal pemphigus vulgaris (Fig. 2b). Direct immunofluorescence stain of the buccal specimen revealed a strong, intercellular, intramucosal deposition of IgG and C3, confirming the diagnosis of pemphigus vulgaris (Fig. 3).