Diagnostic discordance among histopathological reviewers of melanocytic lesions.

BACKGROUND: Histopathological examination is adequate for the diagnosis of most cutaneous melanocytic neoplasms. However, there is a subset that is either difficult to definitively diagnose or would have diagnostic disagreement upon review by multiple dermatopathologists if a more exhaustive review was performed. METHODS: Melanocytic lesions underwent an independent, blinded diagnostic histopathological review of hematoxylin and eosin-stained sections. Each lesion was reviewed by three to six dermatopathologists and categorized as benign, malignant, or unknown malignant potential (UMP). Diagnoses were grouped as concordant (all the same designation); opposing (received benign and malignant designations); majority (single designation with the highest number of diagnoses, no benign/malignant opposing designations); and non-definitive (equal number of non-opposing designations [i.e., benign/UMP or malignant/UMP]). Lesions with equivocal designations (concordant or majority UMP, opposing, majority, and non-definitive) were utilized in a patient treatment model of projected surgical treatment discrepancies. RESULTS: In total, 3317 cases were reviewed, and 23.8% of lesions received equivocal diagnoses. Of these, 7.3% were majority benign, 4.8% were majority malignant, 2.7% were majority UMP, 0.5% were concordant UMP, 6.9% were opposing, and 1.6% were non-definitive. Patient treatment models of those with equivocal lesions (n = 788) revealed a potential of overall surgical treatment variations ranging from 18% to 72%, with the highest variation amongst lesions with opposing, non-definitive, or majority UMP (40%-72%) diagnoses. CONCLUSION: Histopathologic review in this large cohort demonstrated substantial diagnostic variation, with 23.8% of cases receiving equivocal diagnoses. We identified diagnostic ambiguity even in lesions where a definitive diagnosis was previously rendered by a single real-world dermatopathologist. The combined clinical impact of diagnostic discordance or a final diagnosis of UMP is highlighted by high diagnosis-dependent treatment variation in the patient treatment model, which could be underreported in a real-world setting, where review by more than one to two dermatopathologists is relatively rare.

Primary cutaneous SMARCA4-deficient undifferentiated malignant neoplasm: A rare case report and literature review.

Primary cutaneous SMARCA4-deficient undifferentiated malignant neoplasm (SD-UMN) is a rare and recently described entity characterized by the loss of expression of the SMARCA4 (BRG1) protein, which is involved in chromatin remodeling. SD-UMN presents a diagnostic challenge due to its rarity and unique histopathological and immunohistochemical features. In this report, we present a case of primary cutaneous SD-UMN in a 67-year-old man who presented with a rapidly growing, ulcerated, and bleeding nodule on his right cheek. Histopathological examination revealed a highly cellular dermal tumor consisting of pleomorphic epithelioid cells with prominent mitotic figures and necrosis, lacking any morphological evidence of differentiation. Immunohistochemical analysis showed a complete loss of SMARCA4 and SMARCA2 expression, while INI-1 expression remained intact. p53 was diffusely expressed, and p16 was completely absent. In addition, a range of markers, including high-molecular-weight cytokeratin, p63, SOX10, INSM1, MCPyV, NKX2.2, CD99, CDX2, CD56, ERG, NUT, desmin, androgen receptor, chromogranin, CD34, and CD43 were all negative. To date, only two cases of primary cutaneous SMARCA4-deficient undifferentiated tumors have been reported in the literature. Therefore, this case report adds to the limited body of knowledge on the clinical and histopathological features of this novel entity. The report highlights the importance of considering SD-UMN in the differential diagnosis of undifferentiated cutaneous tumors.

IgA Vasculitis Associated With COVID-19.

IgA vasculitis, also known as Henoch-Schonlein Purpura (HSP), is an inflammatory disorder of small blood vessels that can present with palpable purpura, arthralgias, abdominal pain, and kidney disease. It is most commonly found in pediatric patients after an inciting infection but has been seen across all ages and associated with certain drugs and vaccines. COVID-19 has been associated with various cutaneous manifestations, but HSP is a rarely reported one. We present a case of a 21-year-old female presenting with a petechial rash found to be seronegative IgA vasculitis presenting concurrently with dyspnea secondary to COVID-19. She was initially seen by an outside practitioner, tested negative for COVID, and was prescribed a course of oral prednisone. Shortly thereafter, she visited the ED for worsening shortness of breath and tested positive for COVID-19, for which she received Paxlovid. Biopsy after a visit to a dermatologist confirmed intramural IgA deposition on immunofluorescence, and she was tapered off prednisone and started on azathioprine.

A plague passing over: Clinical features of the 2022 mpox outbreak in patients of color living with HIV.

INTRODUCTION: Compared with previous geographically localized outbreaks of monkeypox (MPOX), the scale of the 2022 global mpox outbreak has been unprecedented, yet the clinical features of this outbreak remain incompletely characterized. METHODS: We identified patients diagnosed with mpox by polymerase chain reaction (PCR; n = 36) from July to September 2022 at a single, tertiary care institution in the USA. Demographics, clinical presentation, infection course, and histopathologic features were reviewed. RESULTS AND CONCLUSION: Men who have sex with men (89%) and people living with HIV (97%) were disproportionately affected. While fever and chills (56%) were common, some patients (23%) denied any prodromal symptoms. Skin lesions showed a wide range of morphologies, including papules and pustules, and lesions showed localized, not generalized, spread. Erythema was also less appreciable in skin of colour patients (74%). Atypical clinical features and intercurrent skin diseases masked the clinical recognition of several cases, which were ultimately diagnosed by PCR. Biopsies showed viral cytopathic changes consistent with Orthopoxvirus infections. All patients in this case series recovered without complications, although six patients (17%) with severe symptoms were treated with tecovirimat without complication.

Sarcoidosis Coexisting With Distinct Forms of Alopecia on the Scalp: A Case Series.

ABSTRACT: Sarcoidosis is an idiopathic multisystem inflammatory disease that can affect virtually any part of the body. Often, it can initially present solely in the skin. Histologically, it is characterized by noncaseating, 'naked' granulomas in the dermis and subcutaneous tissue. Clinically, sarcoidosis is often referred to as a 'mimicker' of many other pathologic processes because of its wide array of presentations. Occasionally, sarcoidosis can present in the scalp as both a scarring and nonscarring alopecia. There are countless reports of sarcoidosis mimicking various other alopecias including acne keloidalis nuchae, discoid lupus erythematosus, frontal fibrosing alopecia, lichen planopilaris, and alopecia areata totalis. In this case series, we present 2 novel cases of sarcoidosis not just clinically mimicking other forms of alopecia but occurring in conjunction with a separate and histologically distinct primary alopecia.

Ancillary testing for melanoma: current trends and practical considerations.

The diagnosis of melanocytic lesions is aided by ancillary testing, but clinical inspection with the histomorphological assessment on biopsy remains sufficient in most cases. Immunohistochemistry and molecular studies have proven useful for diminishing the pool of histomorphologically borderline lesions, and sequential testing may further improve overall diagnostic performance, but these assays should be used in a stepwise fashion if at all. Ancillary tests vary based on their technology, performance, and practical considerations, including but not limited to the specific diagnostic question, cost, and turn-around time, which impact test selection. This review examines currently used ancillary tests for the purpose of characterizing melanocytic lesions. Both scientific and practical considerations are discussed.

Gene Expression Signatures in Inflammatory and Sclerotic Morphea Skin and Sera Distinguish Morphea from Systemic Sclerosis.

Morphea is an inflammatory fibrotic disorder of the skin that has been likened to systemic sclerosis (SSc). We sought to examine the molecular landscape of morphea by examining lesional skin gene expression and blood biomarkers and comparing the gene expression profiles with those from site-matched nonlesional and SSc lesional skin. We found the morphea transcriptome is dominated by IFN-γ-mediated T helper 1 immune dysregulation, with a relative paucity of fibrosis pathways. Specifically, expression profiles of morphea skin clustered with the SSc inflammatory subset and were distinct from the those of SSc fibroproliferative subset. Unaffected morphea skin also differed from unaffected SSc skin because it did not exhibit pathological gene expression signatures. Examination of downstream IFN-γ-mediated chemokines, CXCL9 and CXCL10, revealed increased transcription in the skin but not in circulation. In contrast to transcriptional activity, CXCL9 was elevated in serum and was associated with active, widespread cutaneous involvement. Taken together, these results indicate that morphea is a skin-directed process characterized by T helper 1 immune-mediated dysregulation, which contrasts with fibrotic signatures and systemic transcriptional changes associated with SSc. The similarity between morphea and the inflammatory subset of SSc on transcriptional profiling indicates that therapies under development for this subset of SSc are also promising for treatment of morphea.

CXCL9 Links Skin Inflammation and Fibrosis through CXCR3-Dependent Upregulation of Col1a1 in Fibroblasts.

Morphea is characterized by initial inflammation followed by fibrosis of the skin and soft tissue. Despite its substantial morbidity, the pathogenesis of morphea is poorly studied. Previous work showed that CXCR3 ligands CXCL9 and CXCL10 are highly upregulated in the sera and lesional skin of patients with morphea. We found that an early inflammatory subcutaneous bleomycin mouse model of dermal fibrosis mirrors the clinical, histological, and immune dysregulation observed in human morphea. We used this model to examine the role of the CXCR3 chemokine axis in the pathogenesis of cutaneous fibrosis. Using the REX3 (Reporting the Expression of CXCR3 ligands) mice, we characterized which cells produce CXCR3 ligands over time. We found that fibroblasts contribute the bulk of CXCL9-RFP and CXCL10-BFP by percentage, whereas macrophages produce high amounts on a per-cell basis. To determine whether these chemokines are mechanistically involved in pathogenesis, we treated Cxcl9-, Cxcl10-, or Cxcr3-deficient mice with bleomycin and found that fibrosis is dependent on CXCL9 and CXCR3. Addition of recombinant CXCL9 but not CXCL10 to cultured mouse fibroblasts induced Col1a1 mRNA expression, indicating that the chemokine itself contributes to fibrosis. Taken together, our studies provide evidence that CXCL9 and its receptor CXCR3 are functionally required for inflammatory fibrosis.

Superficial GLI1-amplified mesenchymal neoplasms: Expanding the spectrum of an emerging entity which reaches the realm of dermatopathology.

Mesenchymal neoplasms with GLI1 alterations (rearrangements and/or amplification) have been reported recently in several anatomic locations, which include head and neck, soft tissue, and gastrointestinal tract. Herein, to the best of our knowledge, we describe the first three cases of superficial/subcutaneous mesenchymal neoplasm with GLI1 amplification. The neoplasms exhibited low-grade cytologic features with predominant round cell morphology, glomangioma-like areas and a rich background capillary network. There were two to three mitotic figures per 10 HPF and focal necrosis in one case. The tumors exhibited variable expression of CDK4, MDM2, STAT6, D2-40, CD56 and cyclin D1. p16 had strong and diffuse nuclear and cytoplasmic expression in two cases. Numerous other stains were negative. Fluorescence in situ hybridization detected GLI1, DDIT3, and CDK4 coamplification in all cases, while next generation sequencing did not detect a GLI1 gene fusion. The overall features were compatible with a GLI1-amplified mesenchymal neoplasm. In Case 1 a new distant skin lesion appeared 1 month after the surgery exhibiting similar morphology albeit with a higher mitotic index. In Cases 2 and 3, there is no evidence of local recurrence or systemic disease after 8 years and 1 month of follow-up, respectively. These new cases of superficial GLI1-amplified neoplasm expand its clinical spectrum and enter the realm of dermatopathology. The combination of CDK4, cyclin D1, D2-40, and p16 expression with variable MDM2, STAT6, CD56, and S100 immunoreactivity in a low-grade neoplasm with round/ovoid cytomorphology resembling a vascular or adnexal neoplasm may suggest the possibility of GLI1-amplified neoplasm.

Pilomatrical Acanthoma: An Extremely Rare Intraepidermal Variant of Pilomatricoma.

ABSTRACT: Pilomatrical differentiation can be observed in a variety of benign and malignant tumors, with the most common prototype being pilomatricoma. Pilomatricoma often presents in the deep dermis or subcutis, and the sole involvement of epidermis is extremely rare. In our current case series, specimens from 5 patients were included with an average age of 68 years. All lesions presented as solitary verrucous or keratotic papules on the extremities, with 1 lesion having a prominent horn. All lesions have a variable mixture of basaloid matrical cells and shadow cells, and all lesions express ß-catenin (strong nuclear and cytoplasmic), lymphoid enhancer-binding factor 1 within the matrical component, and pleckstrin homology-like domain family A member 1. The histomorphology and immunoprofile of all lesions are of pilomatrical differentiation, confined to the level of the epidermis. Based on these findings and analogous to the terminology used for other benign intraepidermal proliferations (hidroacanthoma simplex and epidermolytic acanthoma), we propose the term "pilomatrical acanthoma" for these rare lesions.

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.

Autoantigen microarrays reveal myelin basic protein autoantibodies in morphea.

BACKGROUND: Morphea is an autoimmune, sclerosing skin disorder. Despite the recent emphasis on immune dysregulation in morphea, the role of autoantibodies in morphea pathogenesis or utility as biomarkers are poorly defined. METHODS: Autoantigen microarray was used to profile autoantibodies from the serum of participants from the Morphea in Adults and Children (MAC) cohort. Clinical and demographic features of morphea patients with myelin basic protein (MBP) autoantibodies were compared to those without. MBP immunohistochemistry staining was subsequently performed in morphea skin to assess for perineural inflammation in areas of staining. Immunofluorescence staining on mouse brain tissue was also performed using patient sera and mouse anti-myelin basic protein antibody to confirm the presence of MBP antibodies in patient sera. RESULTS: Myelin basic protein autoantibodies were found in greater frequency in morphea (n = 50, 71.4%) compared to systemic sclerosis (n = 2, 6.7%) and healthy controls (n = 7, 20%). Patients with MBP antibodies reported pain at higher frequencies. Morphea skin biopsies, highlighted by immunohistochemistry, demonstrated increased perineural inflammation in areas of MBP expression. Immunofluorescence staining revealed an increased fluorescence signal in myelinated areas of mouse brain tissue (i.e. axons) when incubated with sera from MBP antibody-positive morphea patients compared to sera from MBP antibody-negative morphea patients. Epitope mapping revealed target epitopes for MBP autoantibodies in morphea are distinct from those reported in MS, and included fragments 11-30, 41-60, 51-70, and 91-110. CONCLUSIONS: A molecular classification of morphea based on distinct autoantibody biosignatures may be used to differentially classify morphea. We have identified anti-MBP as a potential antibody associated with morphea due to its increased expression in morphea compared to healthy controls and systemic sclerosis patients.

Pleomorphic Dermal Sarcoma: A Clinical and Histopathologic Emulator of Atypical Fibroxanthoma, but Different Biologic Behavior.

Description Pleomorphic dermal sarcoma (PDS) can clinically and histopathologically mimic atypical fibroxanthoma (AFX). However, it has a more aggressive clinical course with a higher recurrence rate and metastatic potential. This case presentation aims to report a rapidly-growing, exophytic, 4 cm tumor following a non-diagnostic shave biopsy 2 months prior and to highlight distinctive features between PDS and AFX needed to make the correct diagnosis. Like AFX, PDS occurs on the sun-damaged skin of the elderly, usually on the head and neck. Also, like AFX, PDS histopathologically consists of sheets or fascicles of epithelioid and/or spindle-shaped cells, often with multinucleation, pleomorphism, and numerous mitotic figures. Immunohistochemistry cannot distinguish PDS from AFX but is used to exclude other malignancies. PDS can be distinguished from AFX by size (PDS is usually >2.0 cm) and by the presence of more aggressive histopathologic features, such as subcutaneous involvement, perineural and/or lymphovascular invasion, and necrosis. PDS is a rare entity not well documented in the literature with confusing, misleading, and changing nomenclature. PDS is a diagnosis of exclusion made after complete excision of the tumor with the aid of histopathology and immunohistochemistry.

Linear Cutaneous Lupus Erythematosus Following Blaschko's Lines on the Scalp: Additional Cases and Review of the Literature.

Description Alopecia of the scalp has various causes and presentations. However, linear alopecia is unusual and lupus erythematosus presenting as linear alopecia is exceedingly rare. To date, there have been 16 documented cases of linear alopecia diagnosed as chronic cutaneous lupus erythematosus occurring in a linear configuration following Blaschko's lines. We report 2 additional cases and review the clinical and histologic features along with treatment. This Blaschkoid linear variant of cutaneous lupus erythematosus has distinct clinical and histologic characteristics that set it apart from other causes of alopecia and from classic forms of cutaneous lupus. These distinct features include a linear configuration, a younger age of presentation, a disproportionate number of Asians affected, and a paucity of cases with systemic involvement. Histologically, the lesions are characterized by prominent mucin in the dermis and subcutaneous tissues. Blaschkoid linear lupus of the scalp is sufficiently distinctive to suggest the diagnosis on histology alone, in the appropriate clinical context. The most common and successful treatments included systemic and/or combination treatment with oral hydroxychloroquine, oral steroids, and/or intralesional steroids.

Acyclovir-Resistant Anogenital Herpes Simplex Virus in an HIV Patient With Pseudoepitheliomatous Hyperplasia Resembling Squamous Cell Carcinoma.

Background: Herpes simplex virus (HSV) is a common infection. However, it may present atypically when patients are immunocompromised, such as with slowly expanding, long-lasting ulcerative or hypertrophic lesions. The histopathologic finding of pseudoepitheliomatous hyperplasia (PEH) can occur in a variety of situations where there is chronic inflammation and can be seen in patients with chronic HSV. Atypical presentations of HSV, particularly hypertrophic lesions with histopathologic findings of PEH, can be misinterpreted as squamous cell carcinoma, create difficulty in diagnosis and hinder appropriate treatment. Case Description: We report a case of a 59-year-old female with a past medical history of human immunodeficiency virus (HIV), who presented at a dermatology clinic with multiple exophytic ulcerations of varying sizes in the perianal region. The patient was diagnosed with HSV and was started on valacyclovir. Over a several-year period, the patient had multiple recurrences of her HSV lesions with persistent vulvodynia despite prophylactic treatment with valacyclovir. Specimens were collected for culture and sensitivities, which revealed acyclovir resistance. The patient's lesions were biopsied due to concern for possible malignancy. Biopsies revealed prominent PEH. The patient had improvement of her HSV with saucerization, topical imiquimod, and increased doses of prophylactic valacyclovir. Conclusion: Atypical, chronic presentations of HSV are common in immunocompromised patients. Hypertrophic HSV is the least common clinical presentation and can be mistaken for squamous cell carcinoma, creating difficulty in diagnosis. Due to concerns for malignancy, our patient's lesions were biopsied, which revealed prominent PEH. While PEH is benign, it can be misdiagnosed as squamous cell carcinoma on histopathology, particularly when there is clinical suspicion for malignancy. In these cases, the clinician needs to alert the pathologist to the immunosuppressed status of the patient. Detailed evaluation for infectious causes, such as HSV, can avoid misinterpretation and potential surgical and oncological overtreatment.

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.

Human Papillomavirus‒Positive and ‒Negative Vulvar Squamous Cell Carcinoma Are Biologically but Not Clinically Distinct.

Vulvar squamous cell carcinoma pathogenesis is traditionally defined by the presence or absence of human papillomavirus (HPV), but the definition of these groups and their molecular characteristics remain ambiguous across studies. In this study, we present a retrospective cohort analysis of 36 patients with invasive vulvar squamous cell carcinoma where HPV status was determined using RNA in situ hybridization and PCR. Clinical annotation, p16 immunohistochemistry, PD-L1 immunohistochemistry, HPV16 circular E7 RNA detection, and RNA sequencing of the cases were performed. A combination of in situ hybridization and PCR identified 20 cases (55.6%) as HPV positive. HPV status did not impact overall survival (hazard ratio: 1.36, 95% confidence interval = 0.307-6.037, P = 0.6857) or progression-free survival (hazard ratio: 1.12, 95% confidence interval = 0.388-3.22, P = 0.8367), and no significant clinical differences were found between the groups. PD-L1 expression did not correlate with HPV status, but increased expression of PD-L1 correlated with worse overall survival. Transcriptomic analyses (n = 23) revealed distinct groups, defined by HPV status, with multiple differentially expressed genes previously implicated in HPV-induced cancers. HPV-positive tumors showed higher global expression of endogenous circular RNAs, including several circular RNAs that have previously been implicated in the pathogenesis of other cancers.

Melanocytic Panfolliculoma: A Case Report of a Rare Benign Follicular Tumor.

ABSTRACT: Panfolliculomas (PF) are rare, benign, follicular tumors that differentiate toward multiple components of the hair follicle, and several variants have been described. We present a case of a rare pigmented PF presenting on actinically damaged skin in an 83-year-old man, which was clinically concerning for malignancy. This tumor arose near an area of atypical squamous proliferation and has evidence of infundibular, outer root sheath, and matrical differentiation and foci of heavy melanin pigmentation and increased melanocytes. We propose the novel designation of "melanocytic PF," akin to melanocytic matricoma but with panfollicular differentiation.

Rare presentation of inflammatory myofibroblastic tumor on a digit.

Inflammatory myofibroblastic tumors (IMTs) are rare soft tissue neoplasms consisting of a mixture of spindle-shaped myofibroblasts or fibroblasts and a variable inflammatory infiltrate composed of eosinophils, plasma cells, and lymphocytes. Associations with trauma and infectious agents have been proposed, but the etiology is unknown. While IMT predominantly develops in the lungs of pediatric patients or young adults, extrapulmonary IMT is well documented and may occur anywhere. Cutaneous IMT is rare and few have been reported on the hand in the English language. The mean age of onset is 10 years, with a slight female predilection. IMT demonstrates intermediate malignant potential, with a tendency to recur locally. Metastases are rare. According to a recent review, anaplastic lymphoma kinase (ALK) positivity on immunohistochemistry is related to local recurrence, but not distant metastases. We report an unusual case of a 36-year-old male, with a lesion on the right second digit, displaying classic histopathologic and immunohistochemical features of IMT, including ALK staining, and confirmatory fluorescence in situ hybridization-proven ALK gene rearrangement.

A standardized approach to classifying melanocytic neoplasms? Comments on the MPATH-Dx system.

The potential benefits and limitations of the MPATH-Dx classification system for melanocytic neoplasms are presented and discussed.