Diagnostic utility of direct immunofluorescence test panels for cutaneous vasculitis: A scoping review.

BACKGROUND: Due to the immune-mediated nature of non-infectious cutaneous vasculitis, skin biopsy specimens are often submitted for direct immunofluorescence (DIF) testing when vasculitis is considered clinically. However, evidence regarding the clinical value of DIF has not been rigorously appraised. OBJECTIVE: In this scoping review, we aimed to systematically evaluate the peer-reviewed literature on the utility of DIF in vasculitis to assist with the development of appropriate use criteria by the American Society of Dermatopathology. METHODS: Two electronic databases were searched for articles on DIF and vasculitis (January 1975-October 2023). Relevant case series involving more than or equal to three patients, published in English, and with full-text availability were included. Additional articles were identified manually via reference review. Due to study heterogeneity, findings were analyzed descriptively. RESULTS: Of 255 articles identified, 61 met the inclusion criteria. Cumulatively representing over 1000 DIF specimens, several studies estimated DIF sensitivity to be 75%. While vascular immunoglobulin A (IgA) deposits on DIF were associated with renal disease, other systemic associations were inconsistent. Vascular IgG deposition may be overrepresented in ANCA-associated vasculitis. Granular vascular and epidermal basement membrane zone Ig deposition differentiated hypocomplementemic from normocomplementemic urticarial vasculitis. Few studies have assessed the added value of DIF over routine microscopy alone in vasculitis. CONCLUSIONS: This scoping review discovered that DIF testing for vasculitis has been performed not only for diagnostic confirmation of vasculitis but also for disease subtype classification and prediction of systemic associations. Future studies on test sensitivity of DIF compared to that of histopathology are needed.

Clinical Follow-up of Atypical Spitzoid Tumors Analyzed by Fluorescence In Situ Hybridization.

Many neoplasms with spitzoid features remain enigmatic, especially those with intermediate grade features or "atypical spitzoid tumors" (ASTs). Fluorescence in situ hybridization (FISH) has emerged as a complementary technique to conventional microscopy, with certain chromosomal patterns conveying diagnostic information. In this study, we examined 36 ASTs analyzed by FISH for specific abnormalities in chromosomes 6, 9, and 11. Aberrations were detected in 11 cases, 7 of which met FISH criteria for spitzoid melanoma. These had homozygous deletion of 9p21, partial deletion of 11q13, gain of 6p25, and gain of 11q13. All 3 patients with positive sentinel lymph nodes, including one with progression beyond the sentinel lymph node, had homozygous deletion of chromosome 9p21, but there were no deaths in an average of 28 months of follow-up of these cases. Other aberrations in the chromosomal pattern of ASTs were heterozygous deletion of 9p21, partial deletion of 6p23, and tetraploidy. We found that ASTs, including those eventually diagnosed as spitzoid melanoma, had a more indolent course in our cohort than conventional malignant melanoma. Moreover, the addition of FISH results led to a more definitive diagnosis in 7 cases, 4 of which had abnormalities on FISH consistent with spitzoid melanoma.

What's eating you? Cutaneous larva migrans.

This article provides a focused update and clinical review on cutaneous larva migrans (CLM), including atypical clinical presentations and newer management recommendations. The results and recommendations are subject to modification based on future studies.

Helminths: a clinical review and update.

This article provides a focused update and clinical review on select helminth infections. The goal is to report atypical clinical presentations and newer management recommendations. The results and recommendations should be interpreted with the understanding that future studies may alter what is presented.

The staining pattern of pigmented spindle cell nevi with S100A6 protein.

BACKGROUND: Spitz nevi typically show strong diffuse staining with S100A6, whereas staining in melanomas is commonly patchy and weak. To our knowledge, S100A6 has not been studied in pigmented spindle cell nevus (PSCN), considered by many to be a variant of Spitz nevus. METHODS: Forty-six archived PSCNs were stained with S100A6 and then categorized by predominant cell size and staining pattern. RESULTS: Eighteen (55%) of the small cell predominant nevi showed patchy staining, eight showed diffuse staining and seven were negative for S100A6. Two predominantly large-celled 'PSCNs' were diffusely positive and had many histopathological attributes of classical Spitz nevi. On review, these two cases were reclassified as Spitz nevi and excluded from the remainder of this study. Of the nevi with mixed cell size, one had no expression of S100A6. In the remaining tumors, the small cells showed patchy staining in eight (80%) and diffuse staining in two (20%). The large cells showed patchy staining in four (40%) and diffuse staining in six (60%). CONCLUSION: In contrast to the strong diffuse S100A6 staining typical of Spitz nevi, the small spindle cells of PSCN commonly show patchy staining or fail to stain completely. In melanocytic neoplasms composed of small spindle cells, patchy S100A6 staining should not be interpreted as evidence of supporting a diagnosis of melanoma.

Statistical analysis of the concordance of immunohistochemical stains with the final diagnosis in spitzoid neoplasms.

INTRODUCTION: The classification of spitzoid melanocytic tumors can be difficult, and pathologists rely on both histological features and clinical information to arrive at a diagnosis. We proposed that an immunohistochemical panel could be useful in classifying these neoplasms and designed a study to test the independent contribution of the panel to the final diagnosis. METHODS: We identified 121 cases previously signed out either as (1) Spitz nevus, (2) atypical spitzoid neoplasm, favor Spitz nevus, (3) atypical spitzoid neoplasm of uncertain malignant potential, (4) atypical spitzoid neoplasm, favor melanoma, and (5) spitzoid melanoma. The slides were reveiwed in random order by 4 pathologists. For the first review, the pathologists received only hematoxylin and eosin sections and patient age. Subsequently, the same pathologists interpreted the immunohistochemically stained slides (S-100A6, HMB-45, and MIB-1) on the same cases in randomized order without the benefit of either hematoxylin and eosin sections or patient age. The original diagnosis (based on a combination of clinical information, hematoxylin and eosin-stained sections and immunohistochemical stains) was the gold standard used for statistical analysis. The primary aim of the study was to determine the level of agreement between interpretions based on hematoxylin and eosin sections and age, the immunostains alone, and the gold standard, thus providing a measurement of the degree to which each of these elements contributes to the final diagnosis. The agreement between the gold standard and external review was also determined for those cases sent for external review. RESULTS: The generalized kappa statistic was 0.95 for both the hematoxylin and eosin-stained slides alone and the immunohistochemical stains alone, implying a high level of agreement among the 4 pathologists. The combined weighted kappa statistic for the comparison of hematoxylin and eosin sections and patient age to the gold standard was 0.49, and for the immunohistochemically stained slides to the gold standard 0.48, indicating that a diagnosis based on hematoxylin and eosin sections alone or immunostains alone show only a moderate and similar level of agreement with the gold standard diagnosis. Only the most controversial cases were sent for external review. The weighted kappa statistic estimate was 0.30 for the gold standard diagnosis on those cases and the external review. CONCLUSIONS: Spitzoid neoplasms remain a difficult area in dermatopathology and experts frequently disagree on the most challenging cases. An immunohistochemical panel contributes to the diagnosis of spitzoid tumors, and the contribution is statistically similar to that of hematoxylin and eosin sections and age. Interpretation remains subjective, as evidenced by the comparison of the gold standard and external review.

Neurofibroma with clear cell change.

Cutaneous clear cell proliferations and degenerative change have been seen in a variety of entities including nevi, dermatofibromas, fibrous papules, atypical fibroxanthomas, basal cell carcinomas, and squamous cell carcinomas, to name a few. However, there have been no reports of clear cells within neurofibromas. We received a biopsy and excision from a 61-year-old man with a papule on his right lateral clavicle. The initial biopsy showed a proliferation of clear cells that stained positive with S-100 and focally with CD68. A clear cell granular cell tumor was favored. Subsequent excision showed the same population of clear cells as seen on the initial biopsy. Interestingly, a neurofibroma was also present immediately beneath the clear cells with areas of transition. A p75 stain highlighted both populations of cells. This is the first case of neurofibroma with clear cells reported in the literature. We postulate that the clear cells are due to degenerative change.

Is superficial spreading melanoma still the most common form of malignant melanoma?

BACKGROUND: Most epidemiological studies suggest that superficial spreading melanoma is the most common histological subtype of malignant melanoma, but past data may not reflect current patterns of sun exposure or other risk factors. OBJECTIVE: We sought to determine the prevalence of melanoma subtypes among recent specimens in a South Texas dermatopathology practice. RESULTS: Lentigo maligna was the most common subtype of melanoma among the cases studied. Of 771 cases of melanoma reviewed, lentigo maligna and lentigo maligna melanoma accounted for 429 (56%). There were 220 cases of pagetoid (superficial spreading) melanoma (29%). Nodular melanoma with no apparent radial growth phase accounted for 27 cases (4%), and there were 23 cases of acral lentiginous melanoma (3%). The remaining 72 specimens (9%) included cutaneous metastases, spitzoid melanoma, melanoma in situ arising within a nevus, nevoid melanoma, desmoplastic melanoma, and patterns that could not be classified. LIMITATIONS: Although the dermatopathology practice is located in South Texas, most patients are active duty military, military retirees, and military dependents. The majority currently resides in Texas, but the patients have lived in many locations around the world and traveled extensively. Sun exposure patterns and other risk factors may not reflect those of other populations. We were not able to perform subgroup analysis based on ethnicity or skin type as such data were not typically submitted with the specimens. CONCLUSION: Our results challenge the notion that pagetoid (superficial spreading) melanoma is the most common subtype of malignant melanoma, at least in patients with extensive sun exposure. Changing patterns of sun exposure or environmental factors may contribute to the changing epidemiology of malignant melanoma. The current prevalence of subtypes of melanoma should be studied in other populations.

Collision tumor composed of Merkel cell carcinoma and lentigo maligna melanoma.

We report the case of an immunocompetent 79-year-old white man with a history of melanoma in situ on the back with a collision tumor composed of a Merkel cell carcinoma (MCC) and lentigo maligna melanoma on the left cheek. The cells of the MCC expressed cytokeratin 20 (CK 20) in a diffuse cytoplasmic pattern, AE1 and AE3 in a perinuclear dot-like pattern and diffusely with neuron-specific enolase. The tumor cells of the MCC failed to express thyroid transcription factor-1. The atypical melanocytes of lentigo maligna melanoma expressed Melan-A and S-100. At the same visit, a lentigo maligna was diagnosed by excisional biopsy on the right cheek. The variability in expression of CK 20, AE1 and AE3 in MCC are reviewed. Prior reports of MCC in collision with non-melanoma skin cancers are reviewed. Additionally, the role of immunosuppression in the development of MCC is considered.

Basal cell carcinoma of the nail unit.

We report a case of a 70-year-old white male with a basal cell carcinoma of the left thumb nail unit. Excision of the tumor via Mohs micrographic surgery was completed in 2 stages. The defect was repaired with a full thickness skin graft. Five months later the nail unit healed without complications. Prior to this report, 21 cases of basal cell carcinoma have been reported in the world literature. This case, as well as the prior reports, are reviewed with a focus on time to diagnosis, location, excisional technique, and method of repair.

Dissection of immune gene networks in primary melanoma tumors critical for antitumor surveillance of patients with stage II-III resectable disease.

Patients with resected stage II-III cutaneous melanomas remain at high risk for metastasis and death. Biomarker development has been limited by the challenge of isolating high-quality RNA for transcriptome-wide profiling from formalin-fixed and paraffin-embedded (FFPE) primary tumor specimens. Using NanoString technology, RNA from 40 stage II-III FFPE primary melanomas was analyzed and a 53-immune-gene panel predictive of non-progression (area under the curve (AUC)=0.920) was defined. The signature predicted disease-specific survival (DSS P<0.001) and recurrence-free survival (RFS P<0.001). CD2, the most differentially expressed gene in the training set, also predicted non-progression (P<0.001). Using publicly available microarray data from 46 primary human melanomas (GSE15605), a coexpression module enriched for the 53-gene panel was then identified using unbiased methods. A Bayesian network of signaling pathways based on this data identified driver genes. Finally, the proposed 53-gene panel was confirmed in an independent test population of 48 patients (AUC=0.787). The gene signature was an independent predictor of non-progression (P<0.001), RFS (P<0.001), and DSS (P=0.024) in the test population. The identified driver genes are potential therapeutic targets, and the 53-gene panel should be tested for clinical application using a larger data set annotated on the basis of prospectively gathered data.