Dermatopathology Trends in African Americans: A Retrospective Analysis of Biopsies.

ABSTRACT: In a retrospective analysis of biopsies from January 1, 2019 to December 31, 2020, at University Hospitals Cleveland Medical Center, we aimed to determine the frequency of dermatologic conditions biopsied in African Americans (AA). Given that AAs constitute 13.4% of the US population, understanding the skin disease profile within this significant demographic is crucial. From a total of 1701 biopsies collected from 1442 AA patients, benign neoplasms emerged as the most common diagnosis, accounting for 26.7%, predominantly in females. Notably, cutaneous T-cell lymphoma was the most frequently biopsied malignancy, whereas pigmentary disorders were the least common at 1.4%. The study highlighted the higher occurrence of squamous cell carcinoma compared with basal cell carcinoma in AA, contrasting trends in other racial demographics. Moreover, recognizing the unique presentations of skin disorders in different racial backgrounds is essential, especially because disparities have been reported in skin of color training among dermatology residency programs. Understanding these racial differences in skin diseases can assist clinicians in refining their diagnostic approach. Future research could further explore the potential gaps between clinical expectations and histologic findings, improving diagnostic accuracy.

Vitamin D3 and deconvoluting a rash.

BACKGROUNDAdverse drug reactions are unpredictable immunologic events presenting frequent challenges to clinical management. Systemically administered cholecalciferol (vitamin D3) has immunomodulatory properties. In this randomized, double-blinded, placebo-controlled interventional trial of healthy human adults, we investigated the clinical and molecular immunomodulatory effects of a single high dose of oral vitamin D3 on an experimentally induced chemical rash.METHODSSkin inflammation was induced with topical nitrogen mustard (NM) in 28 participants. Participant-specific inflammatory responses to NM alone were characterized using clinical measures, serum studies, and skin tissue analysis over the next week. All participants underwent repeat NM exposure to the opposite arm and then received placebo or 200,000 IU cholecalciferol intervention. The complete rash reaction was followed by multi-omic analysis, clinical measures, and serum studies over 6 weeks.RESULTSCholecalciferol mitigated acute inflammation in all participants and achieved 6 weeks of durable responses. Integrative analysis of skin and blood identified an unexpected divergence in response severity to NM, corroborated by systemic neutrophilia and significant histopathologic and clinical differences. Multi-omic and pathway analyses revealed a 3-biomarker signature (CCL20, CCL2, CXCL8) unique to exaggerated responders that is suppressed by cholecalciferol and implicates IL-17 signaling involvement.CONCLUSIONHigh-dose systemic cholecalciferol may be an effective treatment for severe reactions to topical chemotherapy. Our findings have broad implications for cholecalciferol as an antiinflammatory intervention against the development of exaggerated immune responses.TRIAL REGISTRATIONclinicaltrials.gov (NCT02968446).FUNDINGNIH and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; grants U01AR064144, U01AR071168, P30 AR075049, U54 AR079795, and P30 AR039750 (CWRU)).

Genomic Analysis of Cutaneous CD30-Positive Lymphoproliferative Disorders.

Primary cutaneous CD30+ T-cell lymphoproliferative disorders are the second most common cutaneous lymphomas. According to the World Health Organization, CD30+ T-cell lymphoproliferative disorders include primary cutaneous anaplastic large cell lymphoma (C-ALCL) and lymphomatoid papulosis (LyP) as well as borderline lesions. C-ALCL and LyP are thought to represent two ends of a spectrum of diseases that have different clinical presentations, clinical courses, and prognoses in their classic forms but share the same histology of medium to large CD30+ atypical lymphoid cell infiltrates. Because the behavior of these entities is different clinically and prognostically, we aim to search for oncogenic genomic variants using whole-exome sequencing that drive the development of LyP and C-ALCL. Clinical information, pathology, immunohistochemistry, and T-cell rearrangements on six cases of LyP and five cases of C-ALCL were reviewed to confirm the rendered diagnosis before whole-exome sequencing of all specimens. Both LyP and C-ALCL had recurrent alterations in epigenetic modifying genes affecting histone methylation and acetylation (SETD2, KMT2A, KMT2D, and CREBBP). However, they also harbor unique differences with mutations in signal transducer and activator of transcription gene STAT3 of the Jak/signal transducer and activator of transcription pathway and EOMES, a transcription factor involved in lymphocyte development, only noted in C-ALCL specimens. Genomic characterization of LyP and C-ALCL in this series confirms the role of multiple pathways involved in the biology and development of these lymphomatous processes. The identification of similar aberrations within the epigenetic modifying genes emphasizes common potential development mechanisms of lymphomagenesis within lymphoproliferative disorders being shared between LyP and C-ALCL; however, the presence of differences may account for the differences in clinical course.

Bilateral periorbital leukemia cutis presenting as suspected cellulitis.

Many conditions present with periorbital edema and erythema, mimicking preseptal cellulitis. We report the unique case of a patient with relapsed monoblastic mutant isocitrate dehydrogenase-2 (IDH2) acute myeloid leukemia (AML) who presented with periorbital edema and erythema, unresponsive to antibiotics. Histopathology from punch biopsy was consistent with leukemia cutis. The patient responded rapidly to the initiation of enasidenib, a novel targeted inhibitor of mutant IDH2 enzymes. Our case highlights the importance of considering leukemia cutis in patients with a history of leukemia presenting with periorbital edema and erythema.

Incidence of missing pathology specimens in dermatology.

BACKGROUND: Occasionally specimen containers are received in the dermatopathology laboratory without an accompanying specimen. The consequences in this scenario can range from delay in care and inconvenience to patients to increased morbidity and even mortality. Data regarding incidence and associated characteristics of missing specimens are scant. METHODS: Over a 10-year period (7 January 2010 to 7 January 2020) all cases with a missing specimen in a single academic dermatopathology laboratory and a single dermatopathology practice embedded within a dermatology practice were reviewed. RESULTS: Out of 270,754 specimens received, 83 empty specimen containers were identified for an incidence of 0.031%. There were 14 (0.005%) cases in which patients had a separate procedure and a second container with both specimens in it accompanying the empty container. The most common missing specimen-generating procedures were shave biopsies (51%) with most common clinical diagnosis being unspecified (30%). The most common specimen location from the 97 total specimen bottles containing either zero or two specimens was head/neck (53%). Although no further procedures were performed after the specimen was lost for 48% of cases, re-biopsy occurred for 28%. CONCLUSIONS: Failure to insert specimens into the correct container is rare, but represents a potential significant negative event where vigilance and improvement is required.

Pure and Mixed Desmoplastic Melanomas: A Retrospective Clinicopathologic Comparison of 33 Cases.

BACKGROUND: Pure and mixed desmoplastic melanomas (DMs) may have different natural histories and behaviors. METHODS: We conducted a retrospective review of patients diagnosed with DM at our institution between January 1997 and April 2019. A total of 33 unique DMs were identified and subsequently analyzed based on the histologic type (pure vs. mixed). RESULTS: The majority (57.6%) of our cases were classified as pure histology. Patients with pure DMs were more likely to be men (P = 0.035) and be older than 65 years (P = 0.019) compared with patients with mixed DMs. Patients with mixed DM were more likely to have mitoses present (P = 0.001) compared with patients with pure DM. There were no differences in ulceration, perineural invasion, vascular invasion, or survival between patients with pure and mixed histologic subtypes. In addition, no differences in sentinel lymph node biopsy, radiation, or chemotherapy were noted between the 2 histologic subtypes. Immunohistochemistry showed that 27.3% of the pure DMs stained with Melan-A and HMB45 were positive for these immunomarkers. CONCLUSIONS: Pure and mixed variants of DM were found to have similar clinicopathologic characteristics. Patients with the mixed histologic subtype were more likely to have mitoses, but no difference in the therapeutic management or patient survival was seen between the 2 subtypes.

Spitz nevi in African Americans: A retrospective chart review of 11 patients.

BACKGROUND: Spitz nevi are benign melanocytic neoplasms that typically present as rapidly growing solitary lesions on the head, neck, or lower extremities. Very rare reports have been described in African Americans. METHODS: A single-institution 29-year retrospective review of African American patients diagnosed with Spitz nevi was thoroughly analyzed in order to characterize these rare clinical and histopathologic presentations. RESULTS: Eleven African Americans with spitzoid lesions were identified. Seven (64%) cases were in pediatric patients and nine (82%) were in females. Most lesions were hyperpigmented (73%) and elevated (82%). Six (55%) were compound Spitz nevi, three (27%) were dermal Spitz nevi, and two (18%) were junctional Spitz nevi. Two lesions had more than one atypical feature. Histopathologically, common features were symmetry, sharp circumscription, pagetoid spread (55%) with most being centrally, predominance of epithelioid cells (64%), Kamino bodies (45%), slight pigmentation (46%), maturation of dermal component with depth, and lack of subcutaneous fat involvement or ulceration. Excision was performed on all patients and there were no recurrences although follow-up was limited. CONCLUSION: Awareness of the possibility and various presentations of Spitz nevi in African Americans will help prevent misdiagnosis.

Sentinel Node Biopsy in Young Patients with Atypical Melanocytic Tumors of the Head and Neck.

OBJECTIVE: To examine the diagnostic value of the sentinel lymph node biopsy in pediatric through young adult head and neck melanocytic tumors of unknown malignant potential. STUDY DESIGN: Retrospective case series. SETTING: Single academic institution. SUBJECTS AND METHODS: Demographics, histology, and outcomes were examined in 14 patients aged 4 to 24 years with head and neck melanocytic tumors of unknown malignant potential. Information on age at diagnosis, primary lesion characteristics, and sentinel lymph node biopsy were compared. RESULTS: Of 14 patients meeting criteria for head and neck melanocytic tumors of unknown malignant potential, 8 patients underwent sentinel lymph node biopsy (57%). Of those, 4 biopsies (50%) had positive sentinel nodes. All patients undergoing sentinel lymph node biopsy had primary lesions greater than 1 mm depth or mitotic rate of at least 1 mitosis per mm2. No patients had recurrence of their primary lesion at time of follow-up. CONCLUSION: Our data show a high rate of node-positive sentinel lymph node biopsy for pediatric and young adult head and neck patients with melanocytic tumors of unknown malignant potential, supporting the value of sentinel lymph node biopsy in this population.

Immune checkpoint inhibitor-induced sarcoidosis-like granulomas.

Immune checkpoint inhibitors targeting the cytotoxic T lymphocyte-associated antigen-4 and programmed cell death-1 receptors have transformed the treatment of melanoma and other cancers. These therapies are associated with a number of side effects, including immune-related adverse events. Sarcoidosis-like granulomas (SLGs) are important immune checkpoint inhibitor-related reactions to recognize as SLGs can mimic disease progression and accordingly impact treatment decisions. We systematically review reports of immune checkpoint inhibitor-induced SLGs in cancer patients and discuss potential underlying pathophysiological mechanisms.