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.

A rare case of cutaneous pseudoglandular schwannoma.

Schwannomas are benign tumors that arise from the peripheral nerve sheath. Many variants of schwannomas exist, including plexiform, epithelioid, cellular, glandular, and ancient. The pseudoglandular subtype is extremely rare, as fewer than five cases of cutaneous pseudoglandular schwannomas have been reported based on our literature review. Herein, we report a case of a 64-year-old female who presented with a skin-colored nodule on her right arm for several years. Histopathology showed a superficial and deep dermal nodulocystic neoplasm composed of epithelioid and spindle cells surrounded by a fibrous stroma. The epithelioid cells surrounded multiple spaces suggestive of glandular differentiation, although many of these spaces also contained serum and red blood cells, raising consideration for vascular differentiation. Multiple epithelial markers, including pancytokeratin and epithelial membrane antigen, were all negative, providing no support for an epithelial tumor with true ductal/glandular differentiation. In addition, CD31, CD34, smooth muscle actin, and desmin stains were negative in these spaces, making a vascular neoplasm or smooth muscle tumor unlikely. However, SOX10 and S-100 stains were positive, including in cells lining the pseudoglandular spaces, supporting the diagnosis of pseudoglandular schwannoma. Complete excision was recommended. This case highlights an extremely rare presentation of the pseudoglandular variant of schwannoma.

Disseminated and penile mpox with histopathologic correlation: Two separate case reports.

The 2022-2023 mpox outbreak is a global worldwide concern, especially since the virus was previously mainly localized regionally in Central and West Africa. The infection is typically self-limiting and transmitted by close contact/exposure with infected material. Recent cases have been known to present atypically without prodromal symptoms and initially with skin lesions. The histopathology of mpox lesions is rarely reported. Here, we present two middle-aged males presenting initially with painless skin lesions confirmed for mpox by nucleic acid amplification assay. Skin biopsies of the lesion were available for clinicopathologic correlation. Histopathology demonstrated ulceration with viral cytopathologic changes.

Malignant Melanoacanthoma.

ABSTRACT: Melanoacanthomas are benign variations of seborrheic keratosis that have been known to mimic other common benign and malignant skin lesions. Therefore, the diagnosis typically requires biopsy and careful histologic examination. Here, we present the case of a 25-year-old woman initially diagnosed clinically with an epidermal inclusion cyst, but, on biopsy and further evaluation, was found to have histological features of an atypical or malignant melanoacanthoma. Contrary to typical cases of melanoacanthoma, histologic evaluation revealed atypical findings consistent with malignancy, such as tumor necrosis, marked cytologic atypia and pleomorphism, and numerous mitoses, including atypical forms, features consistent with malignancy (ie, similar to a squamous cell carcinoma in these areas). This report highlights the importance of histological evaluation in diagnosis and treatment of skin lesions because atypical presentations often occur and can delay correct diagnosis and appropriate treatment.

CD30 in Cutaneous Pathology.

ABSTRACT: The discovery of CD30 as a diagnostic marker was essential in the identification of not only some lymphomas but also many other solid tumors and benign reactive conditions. Many CD30+ cutaneous disorders and tumors have been categorized since the identification of the marker. With the design of targeted therapies against CD30+ tumoral cells, the interest in CD30 determination was not only diagnostic but also mainly therapeutic. In this article, we explore the historical aspects of the discovery of CD30 and examine the main CD30-related cutaneous pathology, susceptible of anti-CD30 modern treatments.

The Dermatopathology Books Before Unna.

ABSTRACT: Unna's book on dermatopathology was the one that achieved the greatest recognition in medicine and influenced the largest number of dermatopathologists in Europe at that time. However, several previous texts also gathered the requirements to be considered dermatopathological books. In this manuscript, we briefly examine some of the most relevant features of the dermatopathology books written by Simon, Leloir and Vidal, Auspitz, Bärensprung, and Jackson.

Pagetoid Spread in Basal Cell Carcinoma: Potential for Misdiagnosis.

ABSTRACT: Basal cell carcinomas are one of the most common cutaneous carcinomas and show classical histologic features of basaloid nests with peripheral palisading. Pagetoid and intraepidermal spread has not been described in basal cell carcinoma to the best of our knowledge. We report 5 cases of basal cell carcinoma with classic histologic patterns and overlying basaloid nests and single intraepidermal tumor cells. A panel of immunostains were performed that included CK7, MOC31, CEA-m, EMA, androgen receptor, and Bcl2. Most of our cases were positive for both MOC31 and CK7, and all cases were negative for CEA-m and EMA excluding extramammary Paget disease, one of the most common differential diagnoses. These cases expand the spectrum of findings that can be seen in basal cell carcinoma and can help prevent misdiagnoses of basal cell carcinomas as more aggressive tumors.

Ungual Keratoacanthoma With Features of Regression.

ABSTRACT: Ungual keratoacanthoma (UKA) is an infrequent tumor. Different from keratoacanthoma in other parts of the skin, UKA rarely regresses, and grows aggressively with common destruction of the subjacent phalanx. Reported cases of UKA with features of regression are exceptional, and even dermatopathologists with reputed experience in nail pathology admit to having seen very few cases. We herein report a case of a 77-year-old man who presented a painful subungual lesion on the second finger of the right hand. An x-ray showed evidence of erosion of the subjacent distal phalanx. The patient was highly concerned about the lesion and rejected conservative treatment preferring amputation of the distal phalanx. The histopathologic examination revealed a UKA with features of regression.

Central Centrifugal Cicatricial Alopecia Associated With PDL1 Loss and Increased Expression of Caspase 3: A Case Series.

ABSTRACT: Central centrifugal cicatricial alopecia (CCCA) is a scarring alopecia that disproportionately affects patients with skin of color. Genetic studies have revealed that approximately 30% of CCCAs are associated with peptidyl arginine deiminase 3 misfolding mutations. Patients with CCCA usually have a poor prognosis with progressive and permanent hair loss. To further characterize CCCA, we evaluated the inflammatory milieu, PDL1, and caspase 3 expression. The data support the idea of CCCA being a CD4-predominant T-cell process. The loss of PDL1 and increase in caspase 3 expression raises the possibility of involvement of the PD1/PDL1 pathway in CCCA.

Primary cutaneous epithelioid mesenchymal neoplasm with ACTB-GLI1 fusion: a case report.

Mesenchymal tumors harboring GLI1 gene abnormalities are a rare but distinctive group of neoplasms whose clinicopathologic features are currently evolving. In particular, examples of this tumor with ACTB-GLI1 gene fusion, tentatively termed ACTB-GLI1 epithelioid mesenchymal neoplasm (EMN), show a distinctive monomorphic round-to-epithelioid morphology, nested to trabecular pattern of growth, and S100+/SOX10-/SMA- immunophenotype. We report the first case of this entity arising exclusively in the skin. A 69-year-old man with no prior history of neoplasia presented with a 1.5-cm raised lesion on the left buttock. Histopathologic examination revealed a diffuse dermal proliferation of small, monomorphic, round-to-ovoid cells with hyperchromatic nuclei, focally enlarged nucleoli, and minimal eosinophilic to clear-staining cytoplasm. These cells were arranged in confluent nests and trabeculae in a background of fibrocollagenous to focally myxoid stroma. Immunohistochemical analysis revealed strong positivity for S100 and CD56, and negativity for SOX-10, SMA, Melan-A, HMB-45, and a variety of other markers. Based on the morphology and immunophenotype, molecular studies were performed, which revealed the presence of an ACTB-GLI1 fusion transcript, confirming the diagnosis. Given the morphologic overlap of this tumor with other cutaneous round cell neoplasms and its potential for malignant behavior, ACTB-GLI1 EMN is an important entity for pathologists to recognize.

A rare case of cutaneous interdigitating dendritic cell sarcoma.

Interdigitating dendritic cell sarcomas (IDCSs) are aggressive tumors of dendritic cells, often presenting with lymphadenopathy. Fewer than 10 cases of primary cutaneous IDCS have been reported. Histopathologically, IDCS presents as atypical spindle cells with irregular nuclei, and therefore can be difficult to distinguish from melanoma, follicular dendritic cell sarcoma, and Langerhans cell tumors by H&E examination alone. We report a unique case of a man with cutaneous IDCS that was initially misdiagnosed as melanoma. Having previously undergone an excision of a reported "melanoma" on the neck, he presented with a new growth on the cheek. Histopathologic findings revealed an atypical dermal lymphohistiocytic infiltrate around vessels and cells forming nests along the dermal-epidermal junction. Immunohistochemical stains were strongly positive for S100, fascin, and lysozyme; on the other hand, CD1a, langerin, CD21, CD23, and SOX10 were negative. These immunohistochemical findings were consistent with IDCS, and the patient's prior biopsy specimen was then revisited. Similar staining revealed that lesion also to be a cutaneous IDCS. Follow-up imaging with PET scan was negative for metastases, supporting the diagnosis of primary cutaneous IDCS. Our findings contribute to the limited literature on cutaneous IDCS and highlight a potential pitfall in its diagnosis because of overlapping histopathologic features with melanoma.

PRAME immunohistochemistry of spitzoid neoplasms.

BACKGROUND: Spitzoid melanocytic neoplasms are well known to be diagnostically challenging. Immunohistochemistry (IHC) and molecular approaches have been used as ancillary diagnostic tests. Herein, we investigate the use of PRAME IHC for the assessment of spitzoid melanocytic neoplasms. METHODS: Ten Spitz nevi, 14 atypical Spitz tumors, and 11 spitzoid melanomas were retrieved, and PRAME IHC was scored on a scale of 1-4 (in % quartiles). Intensity of staining was categorized as weak or strong. Cases with no staining received a score of 0. Positive lymph nodes from three spitzoid melanomas were also analyzed. RESULTS: Spitz nevi, atypical Spitz tumors, and spitzoid melanomas had mean PRAME IHC scores of 1.20, 0.93, and 3.36, respectively. The percentage of cases with a score 3 or higher for each category of spitzoid neoplasms are as follows: Spitz nevus (20%), atypical Spitz tumor (0%), and spitzoid melanoma (82%). Among the spitzoid melanomas, three cases had positive sentinel lymph nodes, which showed PRAME score of 2, 4, and 4 in the metastatic deposits. CONCLUSIONS: Previous reports revealed PRAME IHC as useful tool to distinguish benign from malignant melanocytic lesions. The results presented here are concordant with the prior studies, but expand the application of this marker to Spitz nevi/tumors and spitzoid melanomas. The present findings suggest the potential diagnostic utility of PRAME IHC in the assessment of spitzoid melanocytic lesions, particularly in distinguishing spitzoid melanomas from Spitz nevi and atypical Spitz tumors.

A case of histiocytoid angiosarcoma mimicking Rosai-Dorfman disease histopathologically.

There are very few documented cases of histiocytoid angiosarcoma in the literature. We report a rare case of histiocytoid angiosarcoma demonstrating emperipolesis, a histopathologic finding that mimics Rosai-Dorfman disease (RDD). A 77-year-old male presented with a subcutaneous nodule on his left forehead. Microscopic examination of the tumor revealed a dense lymphohistiocytic and plasmacytic infiltrate with large epithelioid cells, many of which showed abundant pale eosinophilic to foamy-appearing cytoplasm, and some of which displayed phagocytosis of intact inflammatory cells and erythrocytes. The tumor also showed significant cytologic atypia and pleomorphism. Immunohistochemical stains showed strong staining of the histiocytoid cells and focal anastomosing-like vascular spaces for CD31 and ERG-1, but were essentially negative for CD68, lysozyme, CD163, S100, and CD1a, consistent with a vascular endothelial tumor. This case expands the spectrum of findings that can be identified in angiosarcomas, and should help to prevent potential misdiagnosis as a less aggressive tumor such as RDD.

Appropriate use criteria for ancillary diagnostic testing in dermatopathology: New recommendations for 11 tests and 220 clinical scenarios from the American Society of Dermatopathology Appropriate Use Criteria Committee.

BACKGROUND: Appropriate use criteria (AUC) provide patient-centered physician guidance in test selection. An initial set of AUC was reported by the American Society of Dermatopathology (ASDP) in 2018. AUC reflect evidence collected at single timepoints and may be affected by evolving evidence and experience. The objective of this study was to update and expand AUC for selected tests. METHODS: RAND/UCLA (RAND Corporation [Santa Monica, CA]/University of California Los Angeles) methodology used includes the following: (a) literature review; (b) review of previously rated tests and previously employed clinical scenarios; (c) selection of previously rated tests for new ratings; (d) development of new clinical scenarios; (e) selection of additional tests; (f) three rating rounds with feedback and group discussion after rounds 1 and 2. RESULTS: For 220 clinical scenarios comprising lymphoproliferative (light chain clonality), melanocytic (comparative genomic hybridization, fluorescence in situ hybridization, reverse transcription polymerase chain reaction, telomerase reverse transcriptase promoter), vascular disorders (MYC), and inflammatory dermatoses (periodic acid-Schiff, Gömöri methenamine silver), consensus by panel raters was reached in 172 of 220 (78%) scenarios, with 103 of 148 (70%) rated "usually appropriate" or "rarely appropriate" and 45 of 148 (30%), "appropriateness uncertain." LIMITATIONS: The study design only measures appropriateness. Cost, availability, test comparison, and additional clinical considerations are not measured. The possibility that the findings of this study may be influenced by the inherent biases of the dermatopathologists involved in the study cannot be excluded. CONCLUSIONS: AUC are reported for selected diagnostic tests in clinical scenarios that occur in dermatopathology practice. Adhering to AUC may reduce inappropriate test utilization and improve healthcare delivery.

Rare Palisading Variant of Dermatofibroma.

ABSTRACT: Dermatofibromas (DFs) are benign lesions that typically present as firm papules or nodules on the legs of young- to middle-aged adults. DFs are histologically characterized by a dermal proliferation of spindled fibrohistiocytic cells forming intersecting fascicles and showing collagen entrapment. The palisading variant of DF was first described in 1986 and often presents as a dome-shaped nodule on the digits. Histologically, palisading DFs demonstrate central areas of nuclear palisading in parallel rows resembling Verocay bodies, with more typical areas of DF located peripherally. We report a case of a 33-year-old Hispanic woman who presented with a history of an asymptomatic, slow-growing lesion on her left arm present since her teenage years. Physical examination revealed a solitary, firm brown-to-white 5-mm papule on the left upper arm. A biopsy was performed and revealed a proliferation of spindle cells palisading around areas of hyalinized collagen. The many histologic variants of DF can sometimes create diagnostic confusion. Previously described cases of palisading DFs in the literature showed palisading resembling Verocay bodies and thus raising concern for a schwannoma or other neoplasm that display a "rippled" pattern. Our case is unique in that the architecture of the palisading areas instead resembled a necrobiotic granulomatous process such as granuloma annulare or a rheumatoid nodule at low power.

Folliculosebaceous Cystic Hamartoma With Prominent Adipose Tissue Resembling Spindle Cell Lipoma.

ABSTRACT: Folliculosebaceous cystic hamartomas (FSCH) are a rare form of cutaneous hamartoma composed of follicular, sebaceous, and mesenchymal elements. These lesions are most often seen in the central face and scalp and rarely exceed 2 cm in size. Here, we report a case of a folliculosebaceous cystic hamartoma with a prominent adipose tissue component resembling a spindle cell lipoma. The patient is a 36-year-old man with a slowly enlarging, flesh-colored, lobulated lesion on his right ala that had been previously biopsied. The clinical differential included a hypertrophic scar or recurrent hamartoma. A full-thickness excisional biopsy was performed, which revealed prominent, large, irregularly shaped, folliculosebaceous structures, including multiple dilated follicles associated with prominent hyperplastic-appearing sebaceous glands, findings consistent with FSCH. The mesenchymal component contained a proliferation of spindle-shaped cells associated with mucin and thickened, ropey-appearing bundles of collagen, features mimicking a spindle cell lipoma. This combination of a folliculosebaceous cystic hamartoma with prominent adipose tissue resembling spindle cell lipoma is unusual and has only been previously reported once in the literature, and therefore, our case contributes to the expanding knowledge of this rare variant of FSCH.

Genetic Studies on a Case of Eruptive Disseminated Spitz Nevus and Review of Other 33 Cases.

ABSTRACT: Eruptive disseminated Spitz nevus is an uncommon presentation of Spitz nevi. Only a few tens of cases have been published and only 6 of them have genetic studies. We present an additional case of a 29-year-old woman with dozens of Spitz nevi which had appeared since she was aged 10 years. The nevi were located on arms, inner thighs, legs, and buttocks. Nine of them were biopsied. Four presented severe atypia. Immunohistochemistry was performed on 5 of the biopsied specimens and was negative for PRAME, ROS-1, PDL-1, pan-TRK, and ALK. Molecular studies on the largest lesion demonstrated no NTRK1, NTRK2, or NTRK3 fusions. FISH study for PTEN showed no alteration in that same lesion. Next-generation sequencing was also negative for any detectable mutations in numerous genes analyzed. In conclusion, it seems reasonable to be cautious when evaluating atypia, even if severe, in cases of eruptive disseminated Spitz nevus.

Varicella Zoster With Pemphigus-like Reaction.

ABSTRACT: We present a case of a 55-year-old man with a rash on his right foot that was biopsied and diagnosed as a Varicella Zoster virus infection with an accompanying positive immunohistochemical study with antiviral antibodies. He concomitantly suffered from a Varicella Zoster virus meningitis. The skin biopsies not only showed clear histologic signs of viral cytopathic effects but also showed intercellular IgG and C3 intraepidermal staining by direct immunofluorescence study, findings which are typically consistent with pemphigus vulgaris. However, the patient did not have any history of pemphigus; there was no mucosal involvement, and serum antibodies to desmoglein 1 and 3 were negative. After discharge, the patient continued to have right-sided foot pain, and he continued the acyclovir treatment.

Combined Poroma and Verruca Plantaris.

ABSTRACT: A 76-year-old female patient presented with a peculiar new exophytic-appearing, flesh-colored skin lesion on her left hallux. Owing to its atypical appearance, the neoplasm was biopsied. Histologic sections demonstrated numerous thickened, anastomosing cord-like structures composed of bland appearing adnexal keratinocytes attached to the epidermis and extending into the superficial dermis. Nearby areas exhibited papillomatosis, epidermal acanthosis, dense hyperparakeratosis, hypergranulosis, and superficial koilocytes, findings consistent with a verruca plantaris. A p16 stain was positive in many of the superficial epidermal keratinocytes. Human papillomavirus typing by in situ hybridization for the most common low-risk and high-risk types was also performed and was negative for these. We herein present an unusual case of a skin lesion which combines features of a poroma with a verruca plantaris. We further review what is known of the relationship between human papillomavirus and poroid neoplasms.

Pigmented Multinucleate Cell Angiohistiocytoma: First Case.

ABSTRACT: Multinucleate cell angiohistiocytoma (MCAH) is a benign vascular and fibrohistiocytic (probably reactive) proliferation with peculiar multinucleate cells which most authors interpret as degenerated macrophages. Several clinical variants of MCAH have been described, some of them with brownish-appearing lesions clinically. However, no histologically identified pigment has been described in the cytoplasm of the multinucleate cells so far. We present a pigmented MCAH with cytoplasmic brownish pigment, which was positive with a Masson-Fontana stain and negative with an iron stain, consistent with melanin, in a 33-year-old woman with multiple papules and plaques on the right elbow, right jawline, and left flank.