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Primary cutaneous gamma/delta T-cell lymphoma (PCγδTCL) is a rare form of cutaneous lymphoma characterized by abnormal clonal proliferation of mature, activated gamma-delta T cells expressing the γδ heterodimer of the T-cell receptor (TCR). As an entity, PCγδTCL has recently undergone diagnostic revision since its introduction in the 2008 WHO classification of cutaneous lymphomas and confirmedin 2016. Nonetheless, diagnosis remains difficult both clinically and histologically, given its broad range of clinical manifestations and immunohistochemical phenotypes. Herein, we present a rare case of CD8+ PCγδTCL with a discussion highlighting theheterogeneity within this entity.

Cutaneous leukocytoclastic vasculitis (LCV) is a disease thought to be related to the presence of immune complex deposition within small blood vessel walls. A 58-year-old female presented with purpuric papules on both legs, occurring concurrent with urinary symptoms. Histologically, an intraepidermal blister with luminal fragmented neutrophils was present. A dermal infiltrate was observed surrounding blood vessels; mild perivascular leukocytoclastic debris favored a diagnosis of LCV. Both direct immunofluorescence and immunohistochemistry staining also favored a diagnosis of LCV. Reactivity of the involved vessels was observed to multiple antibodies and complement, with overexpression of von Willebrand factor, CD15, and CD45. The ribosomal protein Phospho-S6 was also detected within the involved vessels, and on the blister roof and floor. The clinical triggering factor was a urinary infection that had progressed to urosepsis; the symptoms were effectively treated. We present an unusual case, where multiple immune reactions correlate with clinical and histologic changes characteristic of LCV. [ABSTRACT FROM AUTHOR]

Claudin-4 is a key component of tight junctions, which play an important role in the formation of the epidermal barrier by forming a circumferential network in the granular layer that serves as a gatekeeper of the paracellular pathway. The aim of this study is to illustrate claudin-4 immunohistochemical staining patterns of different blistering disorders. We collected 35 cases, including two Hailey–Hailey disease, one Darier disease, three Grover disease, one acantholytic acanthoma, two warty dyskeratoma, 11 pemphigus vulgaris (PV) including six mucosal PV, and two pemphigus foliaceus. For comparison, we included five cases of normal skin, five eczema, and three bullous pemphigoid cases. Claudin-4 demonstrated weak-to-moderate expression in keratinocytes located in the stratum granulosum, keratinocytes surrounding hair follicles, and adnexal glands. Further, claudin-4 exhibited moderate-to-strong membranous staining in disrupted keratinocytes surrounding and within the acantholytic and bullous areas in 16/22 of the acantholytic cases (not seen in the six cases of mucosal PV) and all three bullous pemphigoids. This finding suggests that claudin-4 is upregulated in these conditions, which may be a compensatory response to the disrupted barrier function. This finding could shed light on the molecular mechanisms underlying disrupted barrier function in blistering disorders, independent of the specific underlying disease mechanism. [ABSTRACT FROM AUTHOR]

Over the past decade, molecular and genomic discoveries have experienced unprecedented growth, fundamentally reshaping our comprehension of melanocytic tumors. This review comprises three main sections. The first part gives an overview of the current genomic landscape of cutaneous melanocytic tumors. The second part provides an update on the associated molecular tests and immunohistochemical stains that are helpful for diagnostic purposes. The third section briefly outlines the diverse molecular pathways now utilized for the classification of cutaneous melanomas. The primary goal of this review is to provide a succinct overview of the molecular pathways involved in melanocytic tumors and demonstrate their practical integration into the realm of diagnostic aids. As the molecular and genomic knowledge base continues to expand, this review hopes to serve as a valuable resource for healthcare professionals, offering insight into the evolving molecular landscape of cutaneous melanocytic tumors and its implications for patient care. [ABSTRACT FROM AUTHOR]

Programmed cell death protein 1 (PD-1) plays a pivotal role in immune system regulation, with its expression levels linked to malignancy prognosis. However, existing reports on PD-1 staining in mycosis fungoides (MF) present conflicting findings, and little attention has been given to PD-1 staining in different MF variants. To address this, we conducted a retrospective study, employing immunohistochemistry to examine PD-1 expression in cases of folliculotropic MF and non-folliculotropic MF. We analyzed 24 cases of folliculotropic MF and 18 cases of non-folliculotropic MF, and recorded both the percentage of PD-1-labeled tumor cells and the intensity score (negative, weak, medium, or strong). Our results revealed significant disparity in PD-1 labeling between patch/plaque MF and folliculotropic MF (p = 0.028). Non-folliculotropic MF exhibited higher PD-1 labeling in tumor cells (58.3%) compared to folliculotropic MF (40.2%). Notably, there was no significant difference in PD-1 staining between folliculotropic MF and non-folliculotropic MF when both were in the early stage/indolent disease category. However, when considering the tumor stage, folliculotropic MF exhibited PD-1 staining in tumor cells at a rate of 21.1%, while non-folliculotropic MF showed PD-1 staining in tumor cells at a rate of 46.6% (p = 0.005). Additionally, among folliculotropic MF cases, 13 out of 24 cases displayed differing PD-1 expression patterns between epidermal and dermal components, with preserved PD-1 staining in the epidermal component and loss of staining in the dermal component. Furthermore, consistent with the prior literature, tumor cells with large cell transformations exhibited significantly lower PD-1 labeling (p = 0.017). Our findings showcase the unique PD-1 staining patterns in MF. [ABSTRACT FROM AUTHOR]

Background: Carboxytherapy is defined as intradermal and/or subcutaneous microinjections of sterile purified carbon dioxide into different parts of the body for therapeutic aims. The vasodilatation effect and intradermal collagen reorganization associated with carboxytherapy have advantages for aesthetic dermatology and cosmetology. Objective: In the current article, we have reviewed some of the most important indications of this modality in dermatology and aesthetic dermatology. Method: Our review is a narrative one which has gathered some of the most important indications of carboxytherapy in dermatology and cosmetology. Results: Carboxytherapy has successfully been applied for some dermatologic and cosmetic conditions among which skin aging, cellulite, localized fat deposits, striae distensae, infraorbital hyperpigmentation, scar, lymphedema, androgenetic alopecia, alopecia areata, psoriasis, morphea, and vitiligo are the most important. Conclusion: Carboxytherapy can be considered as a safe, minimally‐invasive modality used for rejuvenation, restoration, and recondition of the skin. [ABSTRACT FROM AUTHOR]

Digital papillary adenocarcinoma (DPA) is a rare neoplasm that can exhibit local recurrence and distant metastasis. We present a series of eight cases of DPA showing two distinct clinical presentations, morphologies, immunophenotypes, and molecular features. Four cases were characterized by painless, slow‐growing nodules located on the digits. The lesions were small, well‐defined, and confined in the dermis. Histopathologically, these tumors were composed of glandular structures lined by cuboidal epithelium with luminal papillary infoldings. Only rare mitotic figures and minimal squamoid differentiation were present, and cellular necrosis was absent. All four cases were positive for the BRAF V600E immunohistochemistry but negative for p16, low‐risk and high‐risk HPV in situ hybridization (ISH). In contrast, the remaining four cases were characterized by painful, rapidly growing masses on the digits. These four lesions were located in the deep dermis and consisted of a solid, tightly packed papillary architecture lined by atypical epithelioid cells with inconspicuous nucleoli. Cellular necrosis, numerous mitotic figures, and prominent squamoid differentiation were seen. All cases were negative for the BRAF V600E IHC. However, they showed strong, patchy to diffuse reactivity for p16 and were positive for low‐risk HPV ISH and negative for high‐risk HPV ISH. Our findings suggest that the current classification of DPA encompasses tumors that show two discrete pathogenic pathways — BRAF mutation or low‐risk HPV infection. DPAs with low‐risk HPV infection exhibit aggressive clinical features, high‐grade morphology, marked squamoid differentiation, and wild‐type BRAF. DPAs with BRAF V600E have less aggressive clinical features, low‐grade morphologic findings, mild to absent squamoid differentiation, and negative HPV infection. [ABSTRACT FROM AUTHOR]

The trichorhinophalangeal syndrome type 1 (TRPS1) immunohistochemical (IHC) stain has increased in use in recent years as a marker for breast carcinomas. The TRPS1 gene is involved in various tissues, including the growth and differentiation of hair follicles. This article seeks to evaluate the IHC expression of TRPS1 in cutaneous neoplasms with follicular differentiation, such as trichoblastoma (TB), trichoepithelioma (TE), and basal cell carcinoma (BCC). IHC studies were performed on 13 TBs, 15 TEs, and 15 BCCs with an antibody against TRPS1. The study found a variable staining expression of TRPS1 in the tumor nests of TB, TE, and BCC. BCCs were distinct in that none of the BCCs demonstrated intermediate or high positivity, while TBs and TEs showed intermediate-to-high positivity in 5/13 (38%) and 3/15 (20%) of cases, respectively. We observed a distinct staining pattern among the mesenchymal cells of TB and TE. We found that TRPS1 highlighted perifollicular mesenchymal cells adjacent to the nests of TB and TE tumor cells. This staining pattern was absent in BCCs, where only scattered stromal cells were positive for TRPS1. Papillary mesenchymal bodies were also highlighted by TRPS1 in TB and TE. TRPS1 stained various parts of the normal hair follicle, including the nuclei of cells in the germinal matrix, outer root sheaths, and hair papillae. TRPS1 may be a useful IHC marker for follicular differentiation. [ABSTRACT FROM AUTHOR]

Melanocytic nevi existing in lymph nodes create a diagnostic challenge by mimicking metastases. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemical (IHC) stain can differentiate one from another. FLI-1 IHC expression has been shown in malignant melanoma with variable sensitivity while melanocytic nevi were reported to be negative. We hypothesized that FLI-1/Melan-A dual IHC staining may be used in the distinction of metastatic melanoma from nodal nevi and can be an alternative and/or complementary to PRAME. In this study, we examined 13 lymph nodes with metastatic melanoma and 13 lymph nodes with benign deposits. We stained all of the lymph nodes with FLI-1, FLI-1/Melan-A dual, and PRAME IHC stains. In addition, we stained paired skin samples of the metastatic lymph nodes with FLI-1 and PRAME. In primary cutaneous melanomas, 11 of 13 were positive for FLI-1 and PRAME expression (85%). Malignant cells in 12 and 13 lymph nodes showed positive expression of PRAME and FLI-1, respectively. Only one case with a nevic cell deposit was weakly positive for FLI-1 and the remaining benign cases were negative for both FLI-1 and PRAME. Our results show that FLI-1/Melan-A dual stain is as sensitive and specific as PRAME in distinguishing lymph nodes with metastatic melanoma from nodal nevi. Further studies with larger case numbers are needed to support our significant results. [ABSTRACT FROM AUTHOR]

Granuloma annulare (GA) is a benign, self-limiting granulomatous inflammatory disease that exhibits different histologic patterns. Infrequently, granuloma annulare can be associated with malignancy, the so-called malignancy-associated granuloma annulare (MGA). In this study, we aimed to compare the clinical and histopathological differences between GA and MGA. We retrospectively reviewed patient charts and identified 35 patients diagnosed with GA and concurrent hematological or solid organ malignancies as a case group. Additionally, we identified 33 patients without any known solid organ or hematological malignancy as a control group. MGA is commonly seen in the seventh decade of life, while GA affects the younger population. MGA is most commonly presented in the extremities of the body. The most common malignancy associated with MGA was chronic lymphocytic leukemia. Prostate cancer was the most common type of solid organ malignancy that was associated with MGA. The most common histopathological pattern seen in MGA was interstitial, comprising half of the cases. Multinucleated giant cells were present in half of the MGA cases and in most of the control group. In the literature, there are no established features that distinguish MGA from GA. Although MGA and GA have overlapping features, in our series, we found that the interstitial pattern was more common in MGA, while the necrobiotic pattern was more common in GA. [ABSTRACT FROM AUTHOR]

Neoplasms of sweat glands and the breast may be morphologically and immunophenotypically similar. A recent study showed that TRPS1 staining is a highly sensitive and specific marker for breast carcinoma. In this study, we analyzed TRPS1 expression in a spectrum of cutaneous sweat gland tumors. We stained five microcystic adnexal carcinomas (MACs), three eccrine adenocarcinomas, two syringoid eccrine carcinomas, four hidradenocarcinomas, six porocarcinomas, one eccrine carcinoma-NOS, 11 hidradenomas, nine poromas, seven cylindromas, three spiradenomas, and 10 syringomas with TRPS1 antibodies. All of the MACs and syringomas were negative. Every cylindroma and two of the three spiradenomas demonstrated intense staining in cells lining the ductular spaces, with negative to relatively weak expression in surrounding cells. Of the 16 remaining malignant entities, 13 were intermediate to high positive, one was low positive, and two were negative. From the 20 hidradenomas and poromas, intermediate to high positivity was revealed in 14 cases, low positivity in three cases, and negative staining in three cases. Our study demonstrates a very high (86%) expression of TRPS1 in malignant and benign adnexal tumors that are mainly composed of islands or nodules with polygonal cells, e.g., hidradenomas. On the other hand, tumors with small ducts or strands of cells, such as MACs, appear to be completely negative. This differential staining among types of sweat gland tumors may represent either differential cells of origin or divergent differentiation and has the potential to be used as a diagnostic tool in the future. [ABSTRACT FROM AUTHOR]

Leukocytoclastic vasculitis is an inflammatory disease of small blood vessels; circulating immune complexes are part of the disease. A 57-year-old female presented with a sudden appearance of palpable purpura with petechial hemorrhages on the lower limbs after taking multiple medications. Skin biopsies were stained for H&E, direct immunofluorescence (DIF) and immunohistochemistry (IHC). The DIF revealed strong staining with multiple immunoglobulins and other markers in small dermal blood vessels, including those around skin appendices The IHC was positive for myeloperoxidase. CD15, myeloperoxidase and HLA-DPDQDR on the upper dermal blood vessels, as well as on inflammatory cells and debris around the vessels. These findings have not been previously documented and may indicate that circulating immune complexes activate the neutrophils. [ABSTRACT FROM AUTHOR]

Bullous lupus erythematosus is an uncommon blistering subepidermal autoimmune disease with characteristic immunopathological nosologic features. A 67-year-old female presented with the sudden appearance of blisters in the upper area of the right chest. Skin biopsies stained with H&E favored the diagnosis of blistering lupus erythematous with a decrease in dermal sebaceous and eccrine glands. Direct immunofluorescence revealed deposits of IgG, complement C3, fibrinogen, IgM, and IgD in the epidermal corneal layer and the basement membrane zone. Reactivity to some dermal endothelial cell junctions and neural receptors was also noted. Also, complement C4 was positive against upper and middle dermal thin fibers. Complement D2 was positive around some enlarged dermal vessels, colocalizing with factor XIIIa. Our case highlights the complex and previously unreported immunologic response features associated with bullous lupus erythematosus. [ABSTRACT FROM AUTHOR]

Background: Cutaneous mixed tumors (CMTs) include benign, atypical, and malignant chondroid syringomas. This spectrum of entities is known to be a part of myoepithelial neoplasms, which display considerable genetic heterogeneity. In a previous report, a malignant chondroid syringoma (MCS) demonstrated PHF1-TFE3 gene fusion and strong TFE3 immunohistochemical (IHC) staining. The authors suggested that the MCS is genetically related to tumors with TFE3 rearrangements such as renal cell carcinoma and might have genetic heterogeneity. In this study, we aim to investigate potential TFE3 gene fusions with TFE3 IHC stain in a spectrum of CMTs. Materials: Eleven benign chondroid syringoma (BCS), one atypical chondroid syringoma (ACS), and one malignant chondroid syringoma cases were identified, stained with TFE3 IHC stain, and interpreted based on preset criteria. Results: ACS and MCS cases did not show any staining. In 7 of 11 BCS cases, weak (1+) staining was observed in less than 20% of the tumor cells and were considered negative. Additionally, in one BCS case, weak (1+) and (2+) staining was shown in approximately 15% and less than 1% of the tumor cells, respectively. Based on our positivity criteria, this case was also interpreted as negative. Conclusions: Our study failed to reveal possible TFE3 gene fusion by IHC staining in benign, atypical, and malignant chondroid syringomas. Although the negative staining in MCS suggests a genetic heterogeneity in this entity, further studies with larger case groups are needed for a more definitive conclusion. [ABSTRACT FROM AUTHOR]

Cutaneous T-cell lymphomas (CTCLs) are rare tumors with no established markers that can reliably distinguish between benign and malignant lesions. Preferentially Expressed Antigen in Melanoma (PRAME) is a cancer/testis antigen that is found in many solid and hematologic malignancies. PRAME overexpression typically portends a poor prognosis and lower chemotherapeutic response. To date, no studies have established a role for PRAME in CTCL. An analysis was performed on 47 cases definitively diagnosed as CTCL: 25 cases of mycosis fungoides, 2 of Sezary syndrome, 5 of CD30+ lymphoproliferative disorder, 7 of primary cutaneous anaplastic large T-cell lymphoma, 3 of primary cutaneous CD4+ small/medium T-cell lymphoproliferative disorder, 1 of subcutaneous panniculitis-like T-cell lymphoma, and 4 of angiocentric T-cell lymphoma. PRAME immunohistochemistry was completely negative in all cases. PRAME expression was not found in any CTCL subtypes, suggesting that the pathogenesis of CTCL is not mediated by PRAME. Further study is required to identify biomarkers that might aid in the diagnosis and prognostication of CTCLs. [ABSTRACT FROM AUTHOR]

Background: Hailey‐Hailey disease (HHD) is an uncommon hereditary and benign skin condition characterized by blisters and erosions on intertriginous areas. It is related to a mutation of the ATP2C1 gene, which encodes a Ca2+ pump. It is characterized by multiple foci of skin acantholysis in the epidermis, with dyskeratosis and suprabasilar clefting. Galectin‐3 is a beta‐galactoside‐binding protein that has an essential role in cell‐to‐cell and cell‐to‐matrix adhesion. We assessed galectin‐3 immunohistochemical expression in HHD to explore its impact on the pathogenesis of this hereditary blistering disorder. Method: In a retrospective study, seven specimens from seven patients diagnosed with HHD were stained with antibodies to galectin‐3. We evaluated the nuclear and cytoplasmic expression of galectin‐3, as well as the staining intensity around blisters and distant normal skin. Results: We observed a significant decrease in cytoplasmic and nuclear expression of galectin‐3 as well as stain intensity around blisters compared with distant normal skin. Conclusions: While the acantholysis process in HHD is related to abnormality in cadherin expression caused by altered Ca2+ pump concentration, lower expression of galectin‐3 may cause the extension of blisters by initiating cell‐to‐cell disassembly in the epidermis. [ABSTRACT FROM AUTHOR]