Comparison of 2 T-Cell Receptor-γ Clonality Assays on Skin Biopsies Suspicious for Mycosis Fungoides.

ABSTRACT: PCR-based fragment analysis of the T-cell receptor (TCR) gene is used extensively in diagnostic labs to assess clonality in T-cell populations in multiple tissue sites. Of the numerous TCR assays that have been reported, studies assessing use on biopsies suspicious for mycosis fungoides specifically are lacking. We compared clonality findings from a previously run 2-tube/2-fluorochrome dye assay to a redesigned 1-tube/1-fluorochrome dye assay on formalin-fixed skin biopsies. Overall, the accuracy of the 2-tube assay was marginally better (75.7% vs. 71.4%), when using clinical history combined with histologic diagnosis as the gold standard. The 2-tube assay had better sensitivity (73.7% vs. 65.8%), while the 1-tube assay had superior specificity (93.8% vs. 87.5%). Clonality results were easier to interpret with the 1-tube assay. In nearly 19% of cases, a change of assays on the same biopsy resulted in a change of clonality interpretation. For laboratories that change TCR-γ clonality assays, follow-up biopsies for mycosis fungoides assessment may result in a change of diagnosis.

Vulvar Lichen Sclerosus Clinical Severity Scales and Histopathologic Correlation: A Case Series.

ABSTRACT: Several vulvar lichen sclerosus (VLS) clinical severity scales have recently been proposed. In this prospective case series, we characterized histopathology in the context of clinical severity in 6 treatment-naïve postmenopausal patients with VLS. The Vulvar Quality of Life Index (VQLI) and an adaptation of the 2018 International Society for the Study of Vulvovaginal Disease Delphi consensus VLS severity score were administered. Vulvar skin punch biopsies were obtained to measure inflammatory density, constituent inflammatory cells, thickness of the stratum corneum and other epidermal layers, dermal edema, and dermal sclerosis. Clinicopathologic correlations were assessed. Two cases demonstrated sparse inflammatory densities, 1 case demonstrated patchy and nodular inflammatory density, 1 case demonstrated dense lichenoid inflammatory density, and 2 cases demonstrated dense lichenoid and epitheliotropic inflammatory densities. Those patients who reported severe pruritus demonstrated the greatest lymphocytic inflammatory densities on histopathological examination. Both cases of ulceration or erosion were associated with severe VQLI scores. Severe VQLI scores were also associated with trends for higher average thickness of the epidermal layers and of dermal sclerosis. Altogether, histopathologic grading of biopsy sites may reflect clinical severity in patients with VLS.

Cutaneous mucormycosis involving a colostomy site.

Cutaneous mucormycosis is a rapidly advancing fungal infection that most commonly occurs due to airborne spread or direct inoculation and requires early detection and prompt treatment for optimal survival. Major risk factors include diabetes, transplantations, malignancies, surgical procedures, and HIV. Diagnostic criteria are based on microscopy and culture. We present an immunocompromised patient with cutaneous mucormycosis that developed in a peristomal ulcer following a hemicolectomy procedure. Histopathologic evaluation was indicative of mucormycosis. Intravenous posaconazole treatment was initiated, but unfortunately, the patient's condition deteriorated and he passed away.

Trends in dermatology eponyms.

Background: Eponyms are ubiquitous in dermatology; however, their usage trends have not been studied. Objective: To characterize the usage of eponyms in dermatology from 1880 to 2020. Methods: Candidate eponyms were collected from a textbook and an online resource. A subset of these eponyms was deemed to be dermatology-focused by a panel of experienced dermatologists. Python scripts were used to permute eponyms into multiple variations and automatically search PubMed using BioPython's Entrez library. Results: The dermatologist panel designated 373 of 529 candidate eponyms as dermatology-focused. These eponyms were permuted into 3159 variations and searched in PubMed. The highest occurring dermatology-focused eponyms (DFEs) in the year 2020 included Leishmania, Behçet syndrome, Kaposi sarcoma, Langerhans cell histiocytosis, and Mohs surgery. Increased DFE usage in the general medical literature parallels the overall increase in the use of other eponyms in the medical literature. However, in the most cited dermatology journals, DFE usage did not increase in the past decade. There were several eponyms with decreased usage. Limitations: This study is limited to the publications in PubMed; only titles and abstracts could be queried. Conclusion: DFEs are increasing in usage in the general medical literature, but the usage of eponyms in the most cited dermatology journals has plateaued.

A Short Isoform of Spermatogenic Enzyme GAPDHS Functions as a Metabolic Switch and Limits Metastasis in Melanoma.

Despite being the leading cause of cancer deaths, metastasis remains a poorly understood process. To identify novel regulators of metastasis in melanoma, we performed a large-scale RNA sequencing screen of 48 samples from patient-derived xenograft (PDX) subcutaneous melanomas and their associated metastases. In comparison with primary tumors, expression of glycolytic genes was frequently decreased in metastases, whereas expression of some tricarboxylic acid (TCA) cycle genes was increased in metastases. Consistent with these transcriptional changes, melanoma metastases underwent a metabolic switch characterized by decreased levels of glycolytic metabolites and increased abundance of TCA cycle metabolites. A short isoform of glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS) lacking the N-terminal domain suppressed metastasis and regulated this metabolic switch. GAPDHS was downregulated in metastatic nodules from PDX models as well as in human patients. Overexpression of GAPDHS was sufficient to block melanoma metastasis, whereas its inhibition promoted metastasis, decreased glycolysis, and increased levels of certain TCA cycle metabolites and their derivatives including citrate, fumarate, malate, and aspartate. Isotope tracing studies indicated that GAPDHS mediates this shift through changes in pyruvate carboxylase activity and aspartate synthesis, both metabolic pathways critical for cancer survival and metastasis. Together, these data identify a short isoform of GAPDHS that limits melanoma metastasis and regulates central carbon metabolism. SIGNIFICANCE: This study characterizes metabolic changes during cancer metastasis and identifies GAPDHS as a novel regulator of these processes in melanoma cells.

Epidermolytic Hyperkeratosis in an Epidermoid (Infundibular) Cyst.

ABSTRACT: Epidermolytic hyperkeratosis (EHK) is an uncommon histopathologic reaction pattern that may represent a primary pathological process or a coincidental finding in a variety of neoplasms. We present a case of EHK in an epidermoid (infundibular) cyst. Histopathologically, EHK demonstrates vacuolar degeneration of keratinocytes in the spinous and granular cell layers, with disrupted cellular boundaries, enlarged basophilic keratohyalin-like granules and amorphous eosinophilic inclusions, along with massive hyperkeratosis. In addition to the morphologic description of EHK, we summarize the diagnoses in which EHK has been reported. Prior cases of EHK in an epidermoid (infundibular) cyst are summarized to compare findings. The significance of incidental EHK in skin lesions is unknown.

Ichthyosiform sarcoidosis: Report of a case and comprehensive review of the literature.

Sarcoidosis is a disease that can affect a multitude of organs and manifest as cutaneous disease. Cutaneous manifestations of sarcoidosis vary widely in morphology, earning the nickname of "great imitator," and the diagnosis often requires clinicopathologic correlation and additional laboratory and radiographic workup. We present the case of a 42-year-old African American woman with ichthyosiform sarcoidosis on the bilateral lower extremities. As one of the rarest specific variants of cutaneous sarcoidosis, ichthyosiform is understudied and has been primarily documented in case reports and series. We undertake a comprehensive review of the literature to identify key clinicopathologic features including the characterization of sites of cutaneous and systemic involvement, as well as typical histopathological findings. Lower extremities were the most involved body site (85.7%). Extracutaneous organ involvement centered around pulmonary (65.7%), lymph node (57.1%), and ocular (31.4%) involvement. Of the histopathological features reported, hyperkeratosis (51.4%) and diminished stratum granulosum (62.9%) were most frequently reported in conjunction with dermal granulomas (100%). We hope that these findings will serve to aid clinicopathological correlation and accurate diagnosis of ichthyosiform sarcoidosis.

Podophyllotoxin Cytological Effects on the Epidermis in Condyloma Acuminatum.

ABSTRACT: Podophyllotoxin (PPT) is used to treat condylomata acuminata and works by destabilizing microtubules within epithelial cells, leading to mitotic arrest in metaphase. PPT-induced changes to the epidermis can cause histological findings mimicking dysplasia. Here, we present a case of vulvar condyloma acuminatum treated with PPT, showing ballooning degeneration, necrotic keratinocytes, and mitotic figures. PPT-treated skin may resemble dysplasia or squamous cell carcinoma in situ due to dyskeratosis and frequent mitoses; however, the synchronicity of mitotic figures in early phases of mitosis, as well as the absence of cellular pleomorphism and atypical mitotic figures, allows for distinction from malignancy. This case demonstrates the importance of understanding the histological changes caused by PPT to prevent misdiagnosis and potential overtreatment.

Pink nodule of the chin: an unusual presentation of metastatic carcinoma.

Renal cell carcinoma (RCC) is the most lethal urological tumor, often because it is widely metastasized at the time of diagnosis. There are reports of cutaneous metastases, most commonly to the head and neck, presenting late after RCC is diagnosed. This case presentation explores a 45-year old female patient with a growing skin lesion on her chin, previously treated as an epidermoid cyst before presenting to dermatology clinic. We present a case of cutaneous metastatic clear cell renal cell carcinoma presenting 7 years after initial diagnosis.

A lobulated mass on the upper back with prominent vasculature: A giant basal cell carcinoma.

Basal cell carcinoma (BCC) is characterized by slow but locally invasive growth. Although there is low metastatic potential, if not treated early, these skin cancers can lead to significant morbidity and mortality. In this case report, we present a man with a neglected BCC that developed into what is termed a giant BCC or one that is greater than 5 cm. This tumor was discovered only upon workup of orthostatic lightheadedness and iron deficiency anemia. Although rare, basal cell carcinoma must be included on the differential of a large cutaneous lesion and may be a source of significant blood loss.

Blastic plasmacytoid dendritic cell neoplasm in a young patient.

Blastic plasmacytoid dendritic cell neoplasm is a rare hematologic neoplasm originating from plasmacytoid dendritic cell precursors that has an aggressive disease course with typically poor prognosis. Herein, we report a man in his early twenties who presented with rapid onset of violaceous nodules and purpuric papules and macules that began on his chest before spreading to his arms, back, face, scalp, and legs. He also exhibited systemic symptoms including weight loss and night sweats. He was diagnosed with blastic plasmacytoid dendritic cell neoplasm and began treatment with aggressive multidrug therapy. Thus far his treatment has resulted in complete resolution of his cutaneous manifestations.

Assessing comfort level with pediatric skin specimens among dermatopathologists and pediatric pathologists: A national cross-sectional survey.

BACKGROUND: Cutaneous histopathologic diagnoses in children often differ from those in adults. Depending on practice setting, these specimens may be evaluated by dermatopathologists or pediatric pathologists. We sought to determine whether comfort level with pediatric dermatopathology is associated with prior training, pediatric dermatopathology exposure during fellowship, career duration, or specimen subtype. METHODS: We surveyed dermatopathologists and pediatric pathologists practicing in the United States. Training and practice variables were evaluated by multivariable regression for association with comfort level. RESULTS: Of the 156 respondents, 72% were dermatopathologists (response rate 11.6%) and 28% were pediatric pathologists (response rate 9.3%). Dermatopathologists reported higher comfort overall (P < .001); this was also true for inflammatory dermatoses and melanocytic neoplasms (P < .001). Thirty-four percent and 75% of dermatopathologists and pediatric pathologists, respectively, reported lower comfort with pediatric skin specimens than their usual cases. Pediatric pathologists were 28% more likely to refer these cases to colleagues. Among dermatopathologists, dermatology-trained were more comfortable than pathology-trained colleagues interpreting inflammatory dermatoses (P < .001). CONCLUSIONS: Pathologists' comfort with pediatric dermatopathology varied significantly based upon prior training, career duration, and specimen subtype. These results suggest opportunities for improving education in this domain.