Faculty Bibliography

BACKGROUND:The role of the mammalian target of rapamycin (mTOR) in hair follicle tumorigenesis is unclear. mTOR controls cell growth and can be activated through ribosomal S6 kinase. Herein, we sought to evaluate the expression of phospho-S6 in six different benign and malignant follicular tumor types. METHODS:test (p<0.05). RESULTS:All malignant neoplasms in our series [8/8 (100%) cases of tricholemmal carcinoma, 1/1 (100%) trichoblastic carcinoma and 1/1 (100%) malignant proliferating tricholemmal tumor] demonstrated a strong and diffuse pattern of staining with phospho-S6 involving 70-90% of tumor cells. By contrast, a minority of benign tumors were positive for phospho-S6 and most stained in a patchy pattern including 12/17 (71%) fibrofolliculomas, 9/20 (45%) trichoepitheliomas and 1/10 (10%) tricholemmomas, involving 30-50%, 5-20%, and 40-50% of tumor cells, respectively. Most pilomatricomas [17/19 (89%)] exhibited a stronger, but distinctive staining pattern, staining mostly the basaloid cells with a multifocal distribution, involving 70-90% of tumor cell. CONCLUSIONS:Phospho-S6 is differentially expressed among benign and malignant hair follicle tumors (p = 0.0044). While malignant tumors show diffuse expression, only a small subset of benign neoplasms were positive, primarily in a patchy distribution.

BACKGROUND AND IMPORTANCE/BACKGROUND:Liposclerosing myxofibrous tumors (LSMFTs) are rare benign fibro-osseous tumors most frequently occurring in the proximal femur. We report the first case of this rare tumor occurring within the calvarium. CLINICAL PRESENTATION/METHODS:Our patient presented with a 2-yr history of enlarging, painless, fixed mass over the left forehead. She underwent surgical resection and the mass was histologically confirmed to be a LSMFT. CONCLUSION/CONCLUSIONS:LSMFT is a rare tumor that should remain on the differential for lesions of the calvarium. When diagnosed, this lesion can be removed with the goal of gross total resection and excellent cosmesis can be achieved.

Superficial/cutaneous malignant peripheral nerve sheath tumor is a rare soft tissue neoplasm that shares morphological, immunohistochemical, and molecular features with spindle/desmoplastic melanoma. We aimed to identify a methylome signature to distinguish these two entities. We analyzed 15 cases of spindle/desmoplastic melanoma and 15 cases of cutaneous malignant peripheral nerve sheath tumor in 23 men and 7 women. DNA from formalin-fixed, paraffin-embedded tissues was extracted and processed using the Illumina Infinium Methylation EPIC array interrogating 866,562 CpG sites. Using a home-grown informatics pipeline, we identified differentially methylated positions between the two entities. Functional network analysis for enrichment signatures was performed using DAVID tools. Identified differentially methylated positions were compared with the Cancer Genome Atlas's cutaneous melanoma dataset and a recently published malignant peripheral nerve sheath tumor dataset to assess the specificity of the identified signature. Unsupervised hierarchical clustering showed different patterns of methylation in cutaneous malignant peripheral nerve sheath tumor and spindle/desmoplastic melanoma. Two probes, cg20783223 and cg13332552, colocalized in the promoter region of BCAT1 and miR-2504. Pathway analysis highlighted enrichment in a subset of genes involved in breast and gastric cancer centered on BCAT1 and downstream activated genes in the mTOR pathway. Our study identifies BCAT1 as a novel methylome signature distinguishing spindle/desmoplastic melanoma from cutaneous malignant peripheral nerve sheath tumor.

Microglandular adenosis (MGA) is a rare breast lesion reported to be associated with invasive carcinoma in up to 20-30% of cases, and has been proposed as a non-obligate precursor to basal-like breast cancers. We identified a case of matrix-producing metaplastic carcinoma with morphologic and immunohistochemical evidence of progression from MGA to atypical MGA (AMGA), carcinoma in situ (CIS) and invasive carcinoma. We performed whole exome sequencing of each component (MGA, AMGA, CIS and cancer) to characterize the mutational landscape of these foci. There was significant copy number overlap between all foci, including a segmental amplification of the CCND1 locus (partial chromosome 11 trisomy) and MYC (8q24.12-13). Using a bioinformatics approach, we were able to identify three putative mutational clusters and recurrent, stop-gain non-synonymous mutations in both ZNF862 and TP53 that were shared across all foci. Finally, we identified a novel deleterious splice-acceptor site mutation of chr5:5186164G>T (chromosome 5p15) encoding the gene, ADAMTS16, in the invasive component.

BACKGROUND:Erythema elevatum diutinum (EED) is a rare vasculitis with variable clinical presentation which diagnosis can be challenging. Herein we want to describe the clinicopathological spectrum of findings in 5 cases of EED. PATIENTS AND METHODS/METHODS:We retrospectively analyzed 5 cases in a single institution collected over a period of 27 years. The clinical history was collected and all the slides were examined in order to determine the histopathological characteristics of the lesions. RESULTS:The mean age of our patients is 56.6 years. Two of five patients were females and with lesions showing predilection for the upper-extremities. The most common presentation was of an erythematous plaque on the extensor surfaces. Three patients had a history of neoplasm. All cases showed leukocytoclastic damage consistent with EED. CONCLUSION/CONCLUSIONS:Our findings suggest that EED shows a heterogeneous clinical and pathological presentation which can show an overlap with granulomatous dermatoses and mixed connective tissue diseases. Scalp lesions can occur and can mimic granulomatous dermatoses. The finding of EED in benign and malignant solid tumors in three of our patients begs the question whether there is an association between EED and such solid neoplasms.

Cutaneous metastases are not particularly common compared to metastases to other system organs, but they are an important entity to diagnose correctly given their prognostic implications. Clinically cutaneous metastases can mimic more common dermatologic disorders (e.g. cysts, adnexal tumors, lipomas, cellulitis, vascular tumors, etc.) that may result in diagnosis delay if not considered. An understanding of the clinical spectrum as well as advances in histopathologic assessment of skin metastases is vital to establish the correct diagnosis. Herein we review the clinical, histopathologic, and prognostic salient findings of three different types of cutaneous metastases: carcinomas, melanomas, and sarcomas. We also highlight important immunohistochemical studies and molecular platforms that assist in determining the primary site of origin and/or the line of differentiation.