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Background: Skin aging as a continuous and irreversible process is mainly the result of alterations of function and structure of the dermis. Among the modalities used for treating skin aging, carboxytherapy has been introduced as a safe minimally-invasive method for rejuvenation, reparation, and reconditioning of the skin. Objective: We assessed the efficacy of carboxytherapy for the treatment of intrinsic skin aging through pathological and immunohistochemical (IHC) investigations. Methods: Our study was a split-body, randomized clinical trial on 15 female patients with intrinsic skin aging of the abdomen. Carboxytherapy was performed on one side of the abdomen, weekly for 10 sessions, while the other side was left untreated. Two weeks after the last session, skin biopsies were taken from both sides of the abdomen. Staining with hematoxylin-eosin, Masson-trichrome, and Orcein Giemsa was performed for the assessment of epidermal and dermal thickness, collagen, and elastin organization, respectively. IHC examination was performed for investigation of TGF-ß1 and VEGF. Results: Pathological examination showed a significant increase in epidermal and dermal thickness and re-organization of collagens and elastic fibers with carboxytherapy. IHC examinations revealed a significantly increased expression of TGF-ß1 and VEGF with carboxytherapy. Conclusion: Our study demonstrated the effectiveness of carboxytherapy in treating and reversing intrinsic aging skin through pathological and IHC studies.
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BACKGROUND: Tumor-Stroma Ratio (TSR) has been recognized as a valuable prognostic indicator in various solid tumors. This study aimed to examine the clinicopathological relevance of TSR in Merkel cell carcinoma (MCC) using artificial intelligence (AI)-based parameterization of the stromal landscape and validate TSR scores generated by our AI model versus human-assessed. METHODS: 112 MCC cases with Whole Slide Images (WSIs) were collected from four different institutions. WSIs were first partitioned into 128x128-pixel "mini-patches" then classified by a novel framework, termed Pre-TumOr And STroma (Pre-TOAST) and TOAST, whose output equaled the probability of the mini-patch representing tumor cells rather than stroma. Hierarchical random samplings of 50 mini-patches per region were performed throughout 50 regions per slide. TSR and Tumor-Stromal Landscape (TSL) parameters were estimated by the maximum-likelihood algorithm. RESULTS: Receiver Operating Characteristic (ROC) curves showed the areas under the curve (AUCs) of Pre-TOAST in discriminating classed of interest (COI) including tumor cells, collagenous stroma, and lymphocytes from non-classes of interest (non-COI) including hemorrhage, space, and necrosis were 1.00. AUCs of TOAST in differentiating tumor cells from related stroma were 0.93. MCC stroma was categorized into TSR-high (TSR≥50%) and TSR-low (TSR<50%) using both AI- and human pathology-based methods. AI-based TSR-high subgroup exhibited notably shorter Metastasis-Free Survival (MFS) with a statistical significance of p=0.029. Interestingly, pathologist-determined TSR subgroups lacked statistical significance in Recurrence-Free Survival (RFS), MFS, and Overall Survival (OS) (p>0.05). Density-based spatial clustering of applications with noise (DBSCAN) analysis identified two distinct Tumor-Stroma Landscape (TSL) clusters: TSL1 and TSL2. TSL2 showed significantly shorter RFS (p=0.045) and markedly reduced MFS (p<0.001) compared to TSL1. CONCLUSION: TSL classification appears to offer better prognostic discrimination than traditional TSR evaluation in MCC. TSL can be reliably calculated using an AI-based classification framework and predict various prognostic features of MCC.
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INTRODUCTION: PReferentially expressed Antigen in MElanoma (PRAME) has shown utility in differentiating benign from malignant melanocytic neoplasms. In this study, we investigated the clinical significance of PRAME expression in dysplastic nevi (DN) and nevus-associated melanoma in situ (MIS). METHODS: We included 172 DN and 38 nevus-associated MIS from our institutional archive. PRAME positive expression was defined as nuclear staining in at least 75% of melanocytes. In addition, relevant studies from PubMed and Web of Science were incorporated into a meta-analysis using the random-effects model to assess PRAME expression in MIS and DN. RESULTS: Our institutional data revealed that 71.1% of nevus-associated MIS cases exhibited positive PRAME expression in the MIS components, whereas all DN components were negative for PRAME. 5.7% of cases diagnosed as DN in our cohort demonstrated diffuse positivity for PRAME. Notably, MIS associated with DN displaying epidermal and dermal components displayed a higher likelihood of PRAME positivity compared to those arising on a background of DN with solely epidermal (junctional) components (84% vs. 46%, p = 0.024). The meta-analysis indicated that the pooled PRAME positivity in MIS and DN was 54.5% and 1.9%, respectively. CONCLUSION: PRAME is a valuable immunohistochemical marker for differentiating MIS from DN, particularly in the context of nevus-associated MIS.
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Advanced fluorescence imaging modalities such as confocal microscopy and two photon fluorescence microscopy can provide rapid, real-time histology images, but the mounting of fresh tissue specimens in standard orientations required for diagnosis without embedding and sectioning remains an unsolved problem. Here, we introduce a piston-based specimen holder designed for consistent, even pressure distribution. We improve upon previous designs by incorporating an air piston system with a flexible membrane and wick that extracts fluid during compression. We combine this with support fixtures to aid in the distribution of pressure, enabling imaging of specimens with small surface areas relative to their thickness, such as bisected shave skin biopsies in standard orientation without embedding or sectioning. We image both fresh biopsy specimens and diagnostic Mohs first stage specimens during clinical procedures, demonstrating improved visualization of the tissue surface in real time. Finally, we show that conventional cryosectioning can exaggerate the extent of margin positivity, which can be avoided using the piston-based holder.
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Basal cell carcinoma (BCC) is the most common skin cancer. Skin cancers may present either as a non-invasive tumor or an invasive malignancy. The terminology of carcinoma in situ is used when the tumor is either just limited to epidermis or not present as single cells or nests in the dermis. However, currently the terminology superficial BCC is inappropriately used instead of BCC in situ when the skin cancer is limited to epidermis. In this study we compare the pathologic changes of superficial, nodular, and infiltrative BCCs using electron microscopy to identify the ultrastructural characteristics and validate the previously proposed terminology. Three cases of BCC (superficial BCC, nodular BCC, and infiltrative BCC) diagnosed by dermatopathologists at our institute were selected for review. Paraffin block tissues from these cases were sent for electron microscopy studies which demonstrated disruption of basal lamina in both nodular and infiltrative type of BCC, while it remains intact in BCC superficial type after extensive examination. Therefore, similar to other in situ skin cancers, there is no invasion of the neoplasm in superficial BCC into the dermis. Hence, the older term superficial BCC should be appropriately replaced with the newer terminology BCC in situ.
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The nipple can be affected by many malignant and benign entities. A wide variety of diseases including Paget disease, atopic dermatitis and nipple candidiasis can cause eczema-like changes in the nipple. In cases of diagnostic uncertainty, tissue sampling may be indicated. A true eczematous lesion, such as atopic dermatitis, typically shows a spongiotic dermatitis pattern. Paget disease, on the other hand, presents with infiltration of the nipple epidermis by neoplastic cells. The presence of atypical cells scattered in the epidermis in a pagetoid pattern opens up a histopathological differential diagnosis encompassing squamous cell carcinoma in situ and malignant melanoma, among others. Immunohistochemistry is commonly used to render a diagnosis. The objective of this article is to discuss Paget disease and highlight relevant clinical and histopathological differential diagnoses.
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Adenocarcinoma , Neoplasias de la Mama , Dermatitis Atópica , Eccema , Neoplasias Cutáneas , Humanos , Femenino , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/patología , Diagnóstico Diferencial , Pezones/patología , Neoplasias Cutáneas/diagnóstico , Neoplasias Cutáneas/patología , Eccema/diagnóstico , Eccema/patología , Adenocarcinoma/patología , Neoplasias de la Mama/patologíaRESUMEN
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.
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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.
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Skin aging is a continuous and irreversible process which results in impairment of the skin role as barrier against all aggressive exogenous factors. It mainly manifests by photoaging, laxity, sagging, wrinkling, and xerosis. Carboxytherapy is considered as a safe, minimally invasive modality used for rejuvenation, restoration, and recondition of the skin. In the current study, the efficacy of carboxytherapy in the treatment of skin aging was assessed through investigation of gene expression profile for Coll I, Coll III, Coll IV, elastin, FGF, TGF-ß1, and VEGF. Our study is a 2-split clinical trial in which carboxytherapy was performed on one side of the abdomen in 15 cases with intrinsically skin aging manifestations weekly for 10 sessions, while the other side of the abdomen was left without treatment. Two weeks after the last session, skin biopsies were taken from both the treated and control sides of the abdomen in order to assess gene expression profile by qRT-PCR. The analysis of gene expression levels for all of Coll I, Coll III, Coll IV, elastin, TGF-ß1, FGF and VEGF genes showed a statistically significant difference between the interventional and control groups. The findings for all of these seven genes showed increase in the interventional group, among which Coll IV, VEGF, FGF, and elastin showed the higher mean changes. Our study confirmed the effectiveness of carboxytherapy in treating and reversing the intrinsically aging skin.Clinical Trial Registration Code and Date of Registration: ChiCTR2200055185; 2022/1/2.
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Envejecimiento de la Piel , Humanos , Envejecimiento de la Piel/genética , Elastina , Factor de Crecimiento Transformador beta1/genética , Transcriptoma , Factor A de Crecimiento Endotelial Vascular/genética , Resultado del TratamientoRESUMEN
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.
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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.
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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.
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Alopecia Areata , Dermatología , Estrías de Distensión , Humanos , Piel , Estrías de Distensión/terapia , Dióxido de Carbono/uso terapéutico , Alopecia Areata/tratamiento farmacológicoRESUMEN
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.
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Adenocarcinoma Papilar , Neoplasias Óseas , Carcinoma de Apéndice Cutáneo , Infecciones por Papillomavirus , Lesiones Precancerosas , Neoplasias Cutáneas , Neoplasias de la Tiroides , Humanos , Infecciones por Papillomavirus/patología , Proteínas Proto-Oncogénicas B-raf/genética , Mutación , Adenocarcinoma Papilar/genética , Neoplasias de la Tiroides/patologíaRESUMEN
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.
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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.
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Melanoma , Nevo Pigmentado , Nevo , Neoplasias Cutáneas , Humanos , Antígenos de Neoplasias , Biomarcadores de Tumor/metabolismo , Colorantes , Metástasis Linfática/diagnóstico , Antígeno MART-1 , Melanoma/patología , Nevo/patología , Nevo Pigmentado/patología , Estudios Retrospectivos , Biopsia del Ganglio Linfático Centinela , Neoplasias Cutáneas/patología , Proteína Proto-Oncogénica c-fli-1 , Melanoma Cutáneo MalignoRESUMEN
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.
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Importance: Nonmelanoma skin cancers (NMSCs) are primarily diagnosed through paraffin section histologic analysis of skin biopsy specimens that requires days to weeks before a formal diagnosis is reported. Two-photon fluorescence microscopy (TPFM) has the potential for point-of-care diagnosis of NMSC and other dermatologic conditions, which could enable same-visit diagnosis and treatment. Objective: To demonstrate that TPFM imaging of NMSC can occur within minutes of obtaining biopsies and provide similar histological features to those of conventional histology and evaluate TPFM diagnostic performance with respect to conventional histology. Design, Setting, and Participants: This comparative effectiveness pilot study examined 29 freshly excised biopsies from confirmed NMSC lesions in patients presenting for treatment. Biopsies underwent imaging immediately with TPFM on site at Rochester Dermatologic Surgery (Victor, New York) between October 2019 and August 2021. The imaged biopsies were subsequently submitted for paraffin histology to produce coregistered images. Twelve of these coregistered image pairs (41.4%) were used as a training set. Fifteen (51.7%) were used in a masked evaluation by a board-certified dermatopathologist. Two (6.9%) were excluded from the study before evaluation because they could not be coregistered. Main Outcomes and Measures: Sensitivity, specificity, and accuracy of TPFM for NMSC biopsies were evaluated compared with conventional histology. Results: Fourteen of the 15 biopsy specimens (93.3%) in the evaluation set were identically diagnosed with TPFM and paraffin histology. The TPFM had 100% sensitivity (95% CI, 48%-100%), 100% specificity (95% CI, 69%-100%), and 100% accuracy (95% CI, 78%-100%) for basal cell carcinoma diagnosis. For squamous cell carcinoma diagnosis, TPFM had 89% sensitivity (95% CI, 52%-100), 100% specificity (95% CI, 54%-100%), and 93% accuracy (95% CI, 68%-100%). For overall NMSC diagnosis, TPFM had a 93% sensitivity (95% CI, 66%-100%), 100% specificity (95% CI, 3%-100%), and 93% accuracy (95% CI, 68%-100%). Examination of the 1 discordant pair revealed mismatched imaging planes as the source of error. Conclusions and Relevance: The results of this comparative effectiveness pilot study suggest that TPFM captures histological characteristics of NMSC that are present in conventional histology, which reveals its potential as a rapid, point-of-care diagnostic alternative that does not need extensive sample preparation or retraining for image evaluation. Further validation of TPFM imaging performed for a larger cohort is needed to fully evaluate its diagnostic accuracy and potential effect within the field.
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Carcinoma Basocelular , Dermatología , Neoplasias Cutáneas , Humanos , Proyectos Piloto , Parafina , Carcinoma Basocelular/diagnóstico , Carcinoma Basocelular/patología , Neoplasias Cutáneas/patología , Biopsia , Microscopía FluorescenteRESUMEN
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.
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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.
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Galectina 3/biosíntesis , Regulación de la Expresión Génica , Pénfigo Familiar Benigno/metabolismo , Piel/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Pénfigo Familiar Benigno/patología , Estudios Retrospectivos , Piel/patologíaRESUMEN
We present the case of an 82-year-old female with acantholytic squamous cell carcinoma affecting vulvar skin. The patient had a history of perineal lichen sclerosus for 5 years before presentation. She was referred to a dermatologist for intractable severe pain associated with the lesions. Biopsies showed an infiltrative squamous cell carcinoma with histology consistent with the acantholytic subtype. Acantholytic squamous cell carcinoma is a rare histologic variant characterized by dyscohesive keratinocytes with pseudoglandular formation and dyskeratosis. It is associated with sun-damaged skin and most commonly occurs in the head and neck of elderly men. Few cases have been reported at nondermal sites and non-sun-exposed dermis. The patient underwent a radical vulvectomy and bilateral inguinal node dissection. The 1.6 cm tumor was diffusely acantholytic and pseudoglands were present. The tumor cells were diffusely positive for p63 immunohistochemical stain. As expected at this site, there was no solar elastosis identified histologically. However, vulvar intraepithelial neoplasia and chronic lichen sclerosus were apparent. This case represents a rare histologic subtype of squamous cell carcinoma in an unusual site associated with lichen sclerosus instead of solar elastosis.