ABSTRACT
Anogenital mammary-like glands are normal structures of the anogenital region. Tumors originating from these glands often exhibit a striking resemblance to their mammary gland counterparts. Herein, we present a rare case of adenocarcinoma of mammary gland type in the vulva of a 69-year-old female. Histopathologic examination revealed a complex lesion, which included a large encapsulated papillary carcinoma (EPC) with associated invasive carcinoma of mammary gland type and ductal carcinoma in situ (DCIS). The invasive component consisted mostly of invasive ductal carcinoma of no special type, with a notable focus of invasive mucinous carcinoma. p40 immunostain demonstrated a lack of myoepithelial cells in both the EPC and invasive carcinoma, but such cells expressed p40 around the ducts involved by DCIS. The main component of this lesion, EPC, was characterized by a papillary proliferation within a cystic space surrounded by a fibrous capsule without a myoepithelial layer. The histopathologic features of anogenital EPC closely resemble cutaneous hidradenoma papilliferum. Indeed, there have been a few reports in the literature describing cases where in situ and invasive carcinoma arose from a preexisting hidradenoma papilliferum. As tumors of anogenital mammary-like glands bear a closer resemblance to breast lesions than to skin tumors, we recommend that they be aligned with the classification of well-established breast lesions rather than cutaneous adnexal tumors.
Subject(s)
Breast Neoplasms , Vulvar Neoplasms , Humans , Female , Vulvar Neoplasms/pathology , Vulvar Neoplasms/diagnosis , Vulvar Neoplasms/metabolism , Aged , Breast Neoplasms/pathology , Breast Neoplasms/diagnosis , Diagnosis, Differential , Carcinoma, Papillary/pathology , Carcinoma, Papillary/diagnosis , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Adenocarcinoma/pathology , Adenocarcinoma/diagnosisSubject(s)
Diatomaceous Earth , Diatoms , Myiasis , Humans , Myiasis/diagnosis , Myiasis/pathology , Diatoms/isolation & purification , Diagnosis, Differential , Male , Female , Middle Aged , Skin/pathology , Skin/parasitologyABSTRACT
Background: The elastic scattering spectroscopy (ESS) device (DermaSensor Inc., Miami, FL) is a noninvasive, painless, adjunctive tool for skin cancer detection. Objectives: To investigate the performance of the ESS device in the detection of melanoma. Methods: A prospective, investigator-blinded, multicenter study was conducted at 8 United States (US) and 2 Australian sites. All eligible skin lesions were clinically concerning for melanoma, examined with the ESS device, subsequently biopsied according to dermatologists' standard of care, and evaluated with histopathology. A total of 311 participants with 440 lesions were enrolled, including 44 melanomas (63.6% in situ and 36.4% invasive) and 44 severely dysplastic nevi. Results: The observed sensitivity of the ESS device for melanoma detection was 95.5% (95% CI, 84.5% to 98.8%, 42 of 44 melanomas), and the observed specificity was 32.5% (95% CI, 27.2% to 38.3%). The positive and negative predictive values were 16.0% and 98.1%, respectively. Limitations: The device was tested in a high-risk population with lesions selected for biopsy based on clinical and dermoscopic assessments of board-certified dermatologists. Most enrolled lesions were pigmented. Conclusion: The ESS device's high sensitivity and NPV for the detection of melanoma suggest the device may be a useful adjunctive, point-of-care tool for melanoma detection.
ABSTRACT
ABSTRACT: Preferentially expressed antigen in melanoma (PRAME) immunohistochemistry is currently used to facilitate distinction of benign and malignant melanocytic proliferations. We hypothesized that evaluation of 1 institution's experience with PRAME labeling in a large number of consecutive cases might elucidate additional strengths and potential pitfalls and reveal base rates of positivity versus negativity in 1 academic practice. Pathology reports for all specimens on which PRAME labeling was performed at our institution between January 2021 and May 2022 were retrieved from our database. Eighty percent of conventional malignant melanomas were labeled diffusely positive with PRAME; there were no significant differences in mean age, sex, site, Breslow depth, ulceration status, or American Joint Committee on Cancer pathological tumor stage when comparing diffusely PRAME-positive malignant melanomas with those that lack diffuse labeling. Although no banal melanocytic nevi were labeled with PRAME, 13% of dysplastic nevi were diffusely PRAME positive, with junctional proliferations, severe atypia, male gender, and older age being associated with PRAME positivity. As some but not all ambiguous melanocytic lesions in which malignancy could not be excluded based on morphology alone were diffusely PRAME positive, PRAME's accuracy in predicting malignancy remains unclear to the authors; further study is needed to assess the precision to which PRAME immunohistochemistry can separate benign borderline lesions from their malignant counterparts. Among nonmelanocytic lesions, some poorly differentiated tumors, including atypical fibroxanthomas, can be PRAME positive. This series underscores the importance of clinicopathologic correlation and shows that diffuse PRAME positivity is highest in conventional malignant melanomas (â¼80%, or 8 of 10 lesions), is seen in about half of challenging borderline lesions at our institution, and can be observed in lesions diagnosed as dysplastic nevi by our group (â¼10% or 1 in 10 lesions), as well as in rare poorly differentiated malignancies.
Subject(s)
Dysplastic Nevus Syndrome , Melanoma , Skin Neoplasms , Humans , Male , Antigens, Neoplasm , Diagnosis, Differential , Dysplastic Nevus Syndrome/pathology , Immunohistochemistry , Melanocytes/pathology , Melanoma/diagnosis , Melanoma/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Transcription Factors , FemaleABSTRACT
Distinguishing lupus erythematosus panniculitis (LEP) from subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a diagnostic challenge with important clinical implications. Immunohistochemical expression of interferon regulatory factor 8 (IRF8) has been shown to highlight cells with plasmacytoid dendritic cell differentiation. Considering that the presence of plasmacytoid dendritic cells highlighted by CD123 immunolabeling is a well-described feature that supports LEP over SPTCL, we hypothesized that IRF8 immunohistochemistry can be used as a diagnostic test to improve accuracy in differentiating LEP from SPTCL. In this study, we assessed the expression of IRF8, CD123, and CD20 in 35 cutaneous biopsies from 31 distinct patients, which included 22 cases of LEP and 13 cases of SPTCL. We found that clusters of IRF8-positive cells within the dermis, and away from subcutaneous fat, could discriminate LEP from SPTCL ( P =0.005). Similarly, CD123-positive clusters in any location were observed in LEP but absent in all cases of SPTCL. In addition, we found that dermal CD20-predominant lymphoid aggregates could help discriminate LEP from SPTCL ( P =0.022). As individual assays, IRF8, CD123, and CD20 were highly specific (100%, 100%, and 92%, respectively) though poorly sensitive (45%, 29%, and 50%, respectively). However, a panel combining IRF8, CD123, and CD20, with at least 1 positive marker was more accurate than any individual marker by receiver operating characteristic curve analysis. Our study provides a rationale for potentially including IRF8 as part of an immunohistochemical panel composed of other currently available markers used to differentiate LEP from SPTCL.
Subject(s)
Panniculitis, Lupus Erythematosus , Panniculitis , Humans , Panniculitis, Lupus Erythematosus/diagnosis , Panniculitis, Lupus Erythematosus/metabolism , Panniculitis, Lupus Erythematosus/pathology , Interleukin-3 Receptor alpha Subunit , Panniculitis/diagnosis , Panniculitis/pathology , Interferon Regulatory FactorsABSTRACT
BACKGROUND: Some dysplastic nevi, termed sclerosing nevi with pseudomelanomatous features, may have florid fibroplasia associated with features that cause melanoma to be a prominent consideration in the differential diagnosis. PRAME (PReferentially expressed Antigen in MElanoma) immunohistochemistry (IHC) has been shown to be a useful marker in the distinction of melanoma and nevus. PRAME expression in such sclerosing nevi with pseudomelanomatous features has not been evaluated to our knowledge. METHODS: Thirty-two sclerosing nevi with pseudomelanomatous features were stained with PRAME IHC, with positive labeling defined as staining of >75% of the cytomorphologically atypical lesional cells. RESULTS: All 32 cases had variable cytologic atypia, bridging of elongated rete, fibroplasia, and a vertically oriented trizonal appearance. Some cases (23/32) had centrally located flattening of the rete ridge pattern bilaterally flanked by fibroplasia associated with elongated rete. PRAME labeling was negative (<1% labeling) in 28/32 cases. Four cases, also interpreted as having negative labeling with PRAME, showed only weak nuclear positivity of <50% of the melanocytes within the pseudomelanomatous foci. p16 staining was positive in 28/28 lesions. CONCLUSIONS: Rare sclerosing nevi with pseudomelanomatous features (4/32; ~13%) had weak PRAME labeling of 25%-50% of atypical foci. Twenty-eight of 32 lesions had virtually no labeling with PRAME. PRAME results support classifying sclerosing nevi with pseudomelanomatous features as indolent lesions.
ABSTRACT
Cutaneous lupus erythematosus (CLE) is a disfiguring autoimmune skin disease characterized by an inflammatory infiltrate rich in T cells, which are strongly implicated in tissue damage. How these cells adapt to the skin environment and promote tissue inflammation and damage is not known. In lupus nephritis, we previously identified an inflammatory gene program in kidney-infiltrating T cells that is dependent on HIF-1, a transcription factor critical for the cellular and developmental response to hypoxia as well as inflammation-associated signals. In our present studies using a mouse model of lupus skin disease, we find that skin-infiltrating CD4+ and CD8+ T cells also express high levels of HIF-1. Skin-infiltrating T cells demonstrated a strong cytotoxic signature at the transcript and protein levels, and HIF-1 inhibition abrogated skin and systemic diseases in association with decreased T cell cytotoxic activity. We also demonstrate in human CLE tissue that the T cell-rich inflammatory infiltrate exhibited increased amounts of HIF-1 and a cytotoxic signature. Granzyme B-expressing T cells were concentrated at sites of skin tissue damage in CLE, suggesting relevance of this pathway to human disease.
Subject(s)
Lupus Erythematosus, Cutaneous , T-Lymphocytes, Cytotoxic , Humans , CD8-Positive T-Lymphocytes , Inflammation/metabolism , Skin/pathology , T-Lymphocytes, Cytotoxic/metabolismABSTRACT
Importance: Grover disease (GD), a truncal eruption that typically occurs in older individuals, is exacerbated by sweating, irradiation, cancers, medications, kidney failure, and organ transplantation. The pathobiology of GD remains unknown. Objective: To determine if damaging somatic single-nucleotide variants (SNVs) are associated with GD. Design, Setting, and Participants: In this retrospective case series, we identified consecutive patients from a dermatopathology archive over a 4-year period (January 2007 to December 2011) who had 1 biopsy with a clinical diagnosis of GD confirmed via histopathologic findings and another non-GD biopsy. Participant DNA was extracted from both biopsy tissues and sequenced to high depth with a 51-gene panel to screen for SNVs in genes previously associated with acantholysis and Mendelian disorders of cornification. Analysis took place between 2021 and 2023. Main Outcomes and Measures: Comparative analysis of sequencing data from paired GD and control tissue was employed to identify SNVs predicted to affect gene function, which were exclusive to, or highly enriched in, GD tissue. Results: Overall, 12 of 15 cases of GD (12 men and 3 women; mean [SD] age, 68.3 [10.0] years) were associated with C>T or G>A ATP2A2 SNVs in GD tissue; all were predicted to be highly damaging via combined annotation dependent depletion (CADD) scores, and 4 were previously associated with Darier disease. In 9 cases (75%), the GD-associated ATP2A2 SNV was absent from control tissue DNA, and in 3 cases (25%), ATP2A2 SNVs were enriched 4- to 22-fold in GD vs control tissue. Conclusions and Relevance: In this case series study of 15 patients, damaging somatic ATP2A2 SNVs were associated with GD. This discovery expands the spectrum of acantholytic disorders associated with ATP2A2 SNVs and highlights the role of somatic variation in acquired disorders.
Subject(s)
Acantholysis , Ichthyosis , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Aged , Female , Humans , Male , Acantholysis/genetics , Acantholysis/pathology , Darier Disease/genetics , Ichthyosis/diagnosis , Ichthyosis/genetics , Retrospective StudiesABSTRACT
We highlight the utility of interferon regulatory factor 8 (IRF8), a novel marker of monocytic and dendritic cell lineages, in the diagnosis of a case of blastic plasmacytoid dendritic cell neoplasm (BPDCN) presenting initially in the skin. A 60-year-old male with a previous history of myelodysplastic syndrome presented with cutaneous nodules on chest and scalp. A punch biopsy specimen of a skin nodule showed a diffuse dermal infiltrate of atypical mononuclear cells. The neoplastic cells expressed CD4, CD56, CD43, and TdT but showed minimal reaction for TCL-1 and CD123, and were negative for CD34, CD117, and MPO, confounding the diagnosis. IRF8 performed in retrospect was strongly positive. A new punch biopsy specimen of a chest nodule showed the blastoid tumor cells were positive for TCL-1, CD4, and CD56, but dim CD123. Subsequent bone marrow involvement showed blastoid tumor cells with intense positivity for CD123, CD4, and CD56, which was supportive of the BPDCN diagnosis. BPDCN cases with weak or variable CD123 and TCL-1 expression represent a potential diagnostic pitfall. In a recent study, 15 cases of BPDCN showed uniformly strong staining for IRF8, while CD123 was dim or negative in 4 of these 15 cases. We suggest IRF8 may be a useful marker for BPDCN, especially in cases with weak or variable expression of CD123 and TCL1.
Subject(s)
Hematologic Neoplasms , Skin Neoplasms , Male , Humans , Middle Aged , Interleukin-3 Receptor alpha Subunit/metabolism , Dendritic Cells/pathology , Skin Neoplasms/pathology , Interferon Regulatory Factors , Hematologic Neoplasms/pathologyABSTRACT
BACKGROUND: There is considerable variation in the literature regarding the dermatopathologic diagnostic features of and reporting guidelines for actinic keratosis (AK) and cutaneous squamous cell carcinoma (cSCC). OBJECTIVE: To develop consensus recommendations regarding diagnostic criteria, nomenclature, and reporting of AK and cSCC. METHODS: Literature review and cross-sectional multiround Delphi process including an international group of expert dermatopathologists followed by a consensus meeting. RESULTS: Consensus was achieved regarding the key dermatopathologic features necessary for diagnosing cSCC, AK, and associated variants; grading of degree of cellular differentiation in cSCC; utility of immunohistochemistry for diagnosis of cSCC; and pathologic features that should be reported for cSCC and AK. LIMITATIONS: Consensus was not achieved on all questions considered. CONCLUSION: Despite the lack of clarity in the literature, there is consensus among expert dermatopathologists regarding diagnostic criteria and appropriate reporting of AK and cSCC. Widespread implementation of these consensus recommendations may improve communication between dermatopathologists and clinicians, facilitating appropriate treatment of AK and cSCC.
Subject(s)
Carcinoma, Squamous Cell , Keratosis, Actinic , Skin Neoplasms , Humans , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/pathology , Consensus , Cross-Sectional Studies , Keratosis, Actinic/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Distinguishing melanocytic pseudonests encountered in lichenoid dermatoses or lichenoid keratoses from melanoma in situ (MIS) with brisk lichenoid inflammation can prove challenging. METHODS: We designed a case-control study to evaluate the accuracy metrics of PRAME immunohistochemistry to distinguish melanocytic pseudonests in lichenoid dermatoses or keratoses from inflamed MIS. Immunostaining for PRAME was performed on paraffin-embedded formalin-fixed diagnostic tissue using a rabbit monoclonal antibody to PRAME (Abcam), with a 1:3200 dilution on a Leica Bond detection system. RESULTS: Our search identified 21 cases of melanocytic pseudonests (n = 21, 46%) encountered in lichenoid dermatoses and 24 cases of inflamed MIS (n = 24, 53%). Each method of evaluating PRAME immunohistochemistry (PRAME+ clusters, PRAME % of melanocytes by four categories and PRAME+ melanocyte counts per linear mm of epidermal basal layer) showed statistically significant differences between the MIS and the pseudonest cohorts (respectively, p < 0.001; p < 0.001; and p < 0.001). Receiver operating characteristics analysis for PRAME+ melanocyte counts per linear mm of epidermal basal layer revealed an area under the curve of 0.9 ± 0.05 (95% confidence interval 0.9-1.0). When determining an optimal cut-off point for the best Youden index [sensitivity (%) + specificity (%) - 100], the cut-off of 1.0 PRAME+ melanocytes per linear mm showed a sensitivity of 79.2% and specificity of 85.7% (Youden index 0.65) to distinguish MIS from pseudonests. CONCLUSION: PRAME immunohistochemistry may constitute an additional tool for this challenging differential diagnosis.
Subject(s)
Immunohistochemistry , Keratosis, Actinic , Lichenoid Eruptions , Melanoma , Skin Neoplasms , Humans , Antigens, Neoplasm/chemistry , Antigens, Neoplasm/immunology , Case-Control Studies , Diagnosis, Differential , Immunohistochemistry/methods , Keratosis, Actinic/diagnosis , Lichenoid Eruptions/diagnosis , Lichenoid Eruptions/pathology , Melanocytes/cytology , Melanocytes/immunology , Melanoma/diagnosis , Melanoma/pathology , Skin Neoplasms/diagnosis , Skin Neoplasms/pathology , Melanoma, Cutaneous MalignantABSTRACT
BACKGROUND: Histopathologic features of interface dermatitis can occasionally be seen in mycosis fungoides (MF), particularly in early patch-stage disease. MATERIALS AND METHODS: We identified six patients with MF whose early biopsy specimens showed such prominent interface dermatitis that a benign diagnosis was favored. All subsequent specimens were reviewed for these patients, and the histopathologic evolution of disease was documented. Immunohistochemistry (IHC) for CD2, CD3, CD4, CD5, CD7, CD8, CD30, and CD123 was performed retrospectively. Educational archives were reviewed to assess the incidence of interface dermatitis in biopsies otherwise diagnostic of MF. RESULTS: A spectrum of vacuolar and lichenoid patterns of interface change was observed in this series of six patients eventually diagnosed as having MF, and was seen as a recurring pattern in multiple specimens over time. In retrospect, findings described in early MF such as lining up of lymphocytes along the dermal-epidermal junction within the basal layer, papillary dermal fibrosis, and intraepidermal lymphocyte atypia could be appreciated to varying degrees in the confounding specimens. CD123 was negative in all cases, putatively excluding a connective tissue disease (CTD). None of the early biopsies showed loss of pan-T antigens CD2, CD5, and CD7. Forty-six of 164 cases (28%) of MF in an archival study set showed varying degrees of interface dermatitis in the setting of otherwise diagnostic changes of MF. CONCLUSIONS: Early MF can show prominent interface change and mimic inflammatory dermatoses. Histopathologic clues suggestive of MF should be carefully assessed, and IHC for CD123 may be helpful in distinguishing MF from CTD. Repeat biopsies over time may be necessary to arrive at a definitive diagnosis, in conjunction with ancillary studies and strong clinicopathologic correlation.
Subject(s)
Dermatitis , Mycosis Fungoides , Skin Neoplasms , Humans , Skin Neoplasms/pathology , Retrospective Studies , Interleukin-3 Receptor alpha Subunit , Neoplasm Recurrence, Local , Mycosis Fungoides/pathology , Dermatitis/pathologyABSTRACT
Detection of individual cytokines in routine biopsies from patients with inflammatory skin diseases has the potential to personalize diagnosis and treatment selection, but this approach has been limited by technical feasibility. We evaluate whether a chromogen-based RNA in situ hybridization approach can be used to detect druggable cytokines in psoriasis and atopic dermatitis. A series of psoriasis (n = 20) and atopic dermatitis (n = 26) biopsies were stained using RNA in situ hybridization for IL4, IL12B (IL-12/23 p40), IL13, IL17A, IL17F, IL22, IL23A (IL-23 p19), IL31, and TNF (TNF-α). NOS2 and IFNG, canonical psoriasis biomarkers, were also included. All 20 of the psoriasis cases were positive for IL17A, which tended to be the predominant cytokine, although some cases had relatively higher levels of IL12B, IL17F, or IL23A. The majority of cytokine expression in psoriasis was epidermal. A total of 22 of 26 atopic dermatitis cases were positive for IL13, also at varying levels; a subset of cases had significant IL4, IL22, or IL31 expression. Patterns were validated in independent bulk RNA-sequencing and single-cell RNA-sequencing datasets. Overall, RNA in situ hybridization for cytokines appears highly specific with virtually no background staining and may allow for individualized evaluation of treatment-relevant cytokine targets in biopsies from patients with inflammatory skin disorders.