Clinicopathological features, MCPyV status and outcomes of Merkel cell carcinoma in solid-organ transplant recipients: a retrospective, multicentre cohort study.

BACKGROUND: The proportion of Merkel cell carcinomas (MCCs) in solid-organ transplant recipients (SOTR) harbouring Merkel cell polyomavirus (MCPyV) is unknown, as are factors affecting their outcomes. OBJECTIVE: To describe clinicopathological features of MCC in SOTR, investigate the tumoral MCPyV-status and identify factors associated with tumour outcomes. METHODS: Retrospective, international, cohort-study. MCPyV-status was investigated by immunohistochemistry and polymerase chain reaction. RESULTS: A total of 30 SOTR and 44 consecutive immunocompetent patients with MCC were enrolled. SOTR were younger at diagnosis (69 vs. 78 years, P < 0.001). Thirty-three percent of SOTR MCCs were MCPyV-positive vs. 91% of immunocompetent MCCs (P = 0.001). Solid-organ transplantation was associated with an increased cumulative incidence of progression (SHR: 3.35 [1.57-7.14], P = 0.002), MCC-specific mortality (SHR: 2.55 [1.07-6.06], P = 0.034) and overall mortality (HR: 3.26 [1.54-6.9], P = 0.002). MCPyV-positivity and switching to an mTOR inhibitor (mTORi) after MCC diagnosis were associated with an increased incidence of progression (SHR: 4.3 [1.5-13], P = 0.008 and SHR: 3.6 [1.1-12], P = 0.032 respectively) in SOTR. LIMITATIONS: Retrospective design and heterogeneity of SOTR cohort. CONCLUSIONS: MCPyV appears to play a less prominent role in the aetiopathogenesis of MCC in SOTR. SOTR have a worse prognosis than their immunocompetent counterparts and switching to an mTORi after the diagnosis of MCC does not improve progression.

Cutaneous epithelioid haemangiomas show somatic mutations in the mitogen-activated protein kinase pathway.

BACKGROUND: Epithelioid haemangioma (EH) arising from the skin is a benign vascular tumour with marked inflammatory cell infiltration, which exhibits a high tendency to persist and frequently recurs after resection. So far, the underlying pathogenesis is largely elusive. OBJECTIVES: To identify genetic alterations by next-generation sequencing and/or droplet digital polymerase chain reaction (ddPCR) in cutaneous EH. METHODS: DNA and RNA from an EH lesion of an index patient were subjected to whole-genome and RNA sequencing. Multiplex PCR-based panel sequencing of genomic DNA isolated from archival formalin-fixed paraffin-embedded tissue of 18 patients with cutaneous EH was performed. ddPCR was used to confirm mutations. RESULTS: We identified somatic mutations in genes of the mitogen-activated protein kinase (MAPK) pathway (MAP2K1 and KRAS) in cutaneous EH biopsies. By ddPCR we could confirm the recurrent presence of activating, low-frequency mutations affecting MAP2K1. In total, nine out of 18 patients analysed showed activating MAPK pathway mutations, which were mutually exclusive. Comparative analysis of tissue areas enriched for lymphatic infiltrate or aberrant endothelial cells, respectively, revealed an association of these mutations with the presence of endothelial cells. CONCLUSIONS: Taken together, our data suggest that EH shows somatic mutations in genes of the MAPK pathway which might contribute to the formation of this benign tumour.

Metabolic reprogramming and angiogenesis in primary cutaneous Merkel cell carcinoma: expression of hypoxia-inducible factor-1α and its central downstream factors.

BACKGROUND: Metabolic reprogramming and altered gene expression mediated by hypoxia-inducible factors play crucial roles during tumour growth and progression. Nevertheless, studies analysing the expression of hypoxia-inducible factor-1α and its downstream targets in Merkel cell carcinoma (MCC) are lacking but are warranted to shed more light on MCC pathogenesis and to potentially provide new therapeutic options. OBJECTIVES: To analyse the immunohistochemical expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor-A (referred to as VEGF throughout the manuscript), VEGF receptor-2 (VEGFR-2), VEGF receptor-3 (VEGFR-3), glucose transporter-1 (Glut-1), monocarboxylate transporter 4 (MCT4) and carbonic anhydrase IX (CAIX) in primary cutaneous MCC. METHODS: The 16 paraffin-embedded primary cutaneous MCCs (Merkel cell polyomavirus (McPyV) positive/negative: 11/5) were analysed by immunohistochemistry, namely HIF-1α, VEGF, VEGFR-2 (KDR), VEGFR-3 (FLT4), Glut-1, MCT4 and CAIX. An established quantification score (QS) was applied to quantitate the protein expression by considering the percentage of positive tumour cells (0: 0%; 1: up to 1%; 2: 2-10%; 3: 11-50%; 4: >50%) in relation to the staining intensity (0: negative; 1: low; 2: medium; 3: strong). RESULTS: HIF-1α was expressed in all MCCs and predominantly found at the invading edges of tumour margins. The HIF-1α downstream factors Glut-1, MCT4 and CAIX were expressed in 13 of 16 MCC (81%), 14 of 16 MCC (88%) and 16 of 16 MCC (100%), respectively. Interestingly, VEGF and VEGFR-2 were not expressed in tumour cells, whereas VEGFR-3 was expressed in all MCCs. HIF-1α was expressed significantly stronger in McPyV+ tumours (QS: 10.36 ± 2.41) than in McPyV- tumours (QS: 5.40 ± 1.34; P = 0.002). Similarly, VEGFR-3 was also expressed significantly stronger in McPyV+ tumours (QS: 10.00 ± 2.52) than in McPyV- tumours (QS: 5.40 ± 3.43, P = 0.019). CONCLUSIONS: Our data provide first evidence for a role of HIF-1α in induced metabolic reprogramming contributing to MCC pathogenesis. The metabolic signatures of McPyV+ and McPyV- tumours seem to show relevant differences.

The presence of Merkel cell carcinoma polyomavirus is associated with a distinct phenotype in neoplastic Merkel cell carcinoma cells and their tissue microenvironment.

AIMS: Merkel cell carcinoma (MCC) is an aggressive primary neuroendocrine tumor of the skin, associated with Merkel cell polyomavirus (MCPyV) in 49-89% of cases, depending on the country of origin and the techniques of detection. The presence of MCPyV defines heterogeneity in MCC; MCPyV-negative cases bear a much higher mutational load, with a distinct ultraviolet signature pattern featuring C > T transitions, as a consequence of exposure to ultraviolet light radiation. MCC stroma has not been thoroughly studied, although MCC patients benefit from therapy targeting PD1/PDL1. METHODS AND RESULTS: In this study, using Tissue Microarrays and immunohistochemistry, we have analyzed a series of 219 MCC cases in relation to the presence of MCPyV, and confirmed that the presence of MCPyV is associated with changes not only in the neoplastic cells, but also in the composition of the tumor stroma. Thus, MCPyV, found in 101/176 (57,4%) analyzable cases, exhibits changes in its tumor morphology, the density of the inflammatory infiltrate, the phenotype of the neoplastic cells, and the cell composition of the tumor stroma. MCPyV presence is negatively correlated with a higher level of p53 expression, and associated with a very high frequency (86%) of HLA-I expression loss, a higher apoptotic index, and a stroma richer in T-cells, cytotoxic T-cells, macrophages, PDL1-positive macrophages, and B-cells. CONCLUSIONS: Our findings provide evidence of the basic heterogeneity of MCC, supporting the hypothesis that the presence of MCPyV may induce a rich inflammatory response, which is at least partially avoided through loss of HLA-I antigen expression. On the other hand, MCPyV-negative cases show a much higher frequency of stronger p53 expression and, probably, p53 alterations.

Primary pseudomyogenic hemangioendothelioma of bone: case report and review of the literature.

Pseudomyogenic hemangioendothelioma (PMH) represents a multicentric recently characterized tumor type, generally presenting in young adults, of postulated vascular origin and intermediate malignancy. This entity tends to arise in the deep-seated dermal-subcutaneous locations, preferentially limited to one anatomic site, and may extend secondary to bone. PMH restricted to the skeletal system is rare. To our knowledge, only 19 cases with description of both histologic and clinical findings have been reported to date. We report the clinicopathological features of a further intraosseous PMH occurring in a 46-year-old woman involving the right patella. Histologic examination showed an infiltrating growth composed of sheets and fascicles of spindled to epithelioid large cells, with ample eosinophilic cytoplasm, large vesicular nuclei and prominent nucleoli, sometimes resembling rhabdomyoblastic tumor cells, without morphologic signs of vascular differentiation. At immunohistochemical examination, neoplastic cells stained diffusely for AE1/AE3 keratins, vimentin, ERG, FLI-1, INI-1, FOSB with only focal CD31 expression.The morphologic clues leading to the correct diagnosis of intraosseous PMH have been correlated with the data of the literature, and a special emphasis has been given to the differential diagnosis with other neoplasms, particularly epithelioid sarcoma, in order to avoid unnecessary radical surgery and to optimise possible treatment protocols.

[Smooth muscle hamartoma in volar skin]. / Glattmuskelhamartom in volarer Haut.

We report the case of a 12-year-old girl with a smooth muscle hamartoma of the right index finger. Smooth muscle hamartoma (SMH) is a congenital, relatively common disorder typically with predominance of autochthonal arrector pili muscles. An SMH can also rarely originate from smooth muscles of vessels in palmoplantar skin with the absence of pilosebaceous units. Because of overlapping histological features, the possibility of Becker's nevus being identical or associated with SMH has often been suspected by some authors.

Detection of human parvovirus B19 DNA in 22% of 1815 cutaneous biopsies of a wide variety of dermatological conditions suggests viral persistence after primary infection and casts doubts on its pathogenic significance.

BACKGROUND: Human parvovirus B19 (B19V) has been associated with a number of dermatological and systemic conditions, including myocarditis and autoimmune syndromes. OBJECTIVES: To determine the frequency of B19V DNA detection in a large dermatopathology practice, and to characterize the histopathological patterns involved. METHODS: We selected for polymerase chain reaction (PCR) detection of B19V a total of 1815 skin biopsies pertaining to entities allegedly related to B19V, as well as cases suspected clinically of representing paraviral exanthemas. Immunohistochemical detection of B19V viral protein 2 (VP2) was performed in 92 PCR-positive cases. RESULTS: B19V DNA was found by PCR in 402 out of 1825 biopsy specimens (22%). VP2 protein was identified by immunohistochemistry in only three instances of papular purpuric 'gloves-and-socks' syndrome. CONCLUSIONS: As the virus has the capacity to persist in different tissues (including the skin) for long periods, it could represent merely an innocent bystander, so no pathogenetic significance can be inferred from the PCR positivity for B19V in the vast majority of dermatological conditions studied.

Recurrent lipoatrophic panniculitis of children.

BACKGROUND: Recurrent panniculitis in children with lipoatrophy has been loosely described and reported under different names, but has never been systematically evaluated by immunohistochemical stains. OBJECTIVE: To depict the profile of children with recurrent idiopathic panniculitis. METHODS: Study of clinical, histopathological and immunohistochemical features in five cases with recurrent idiopathic panniculitis. RESULTS: Five children with repeated attacks of painful subcutaneous nodules in association with fever, malaise and abdominal pain or arthralgia, with subsequent lipoatrophy were reviewed. In two patients, extensive involvement led to loss of the cutaneous fatty tissue. Laboratory abnormalities included increased acute phase reactants, leukocytosis with mild neutrophilia, microcytic anaemia and elevated liver enzymes. Histopathology showed lobar panniculitis without vasculitis and with a mixed infiltrate, composed of neutrophils, mononuclear cells, lymphocytes, macrophages and myeloid cells. Neutrophils and myeloid cells were more prominent in early lesions, whereas macrophages predominated in late stages, leading to lipophagia and lipoatrophy. Immunohistochemistry showed positive staining for myeloperoxidase around the necrotic adipocytes in early stages and CD68/PGM1 macrophages in late stages. Intense STAT1 staining was observed in the inflammatory infiltrate. All patients improved with methotrexate and corticosteroids. CONCLUSION: We present five cases of lobar panniculitis and lipoatrophy in childhood. The clinico-pathologic presentation shares features with other autoinflammatory diseases.

Diagnostic approach in lymphoplasmacytic plaque.

BACKGROUND: Lymphoplasmacytic plaque (LPP) is a recently described rare skin disease characterized by a dense dermal lymphohistiocytic infiltrate with polyclonal plasma cells. The clinical picture is distinct with reddish to brownish plaque with a predilection for the lower leg. LPP typically affects children. OBJECTIVE: To define clinical and histologic criteria of LPP and to develop a diagnostic flow chart. METHODS: We investigated six of our own LPP cases. Immunoglobulin light chains, IgG, IgG4, CD31, CD163 as a histiocytic marker were examined by immunohistochemistry. PCR-based molecular studies were conducted for borrelia sp., mycobacterial and leishmania sp. Moreover, 10 cases, which have been reported in the literature, were checked for the same features. RESULTS: We could differentiate three main histological patterns (superficial band-like only, [deep] dermal only and mixed). Acanthosis and interface dermatitis are key features in cases with a superficial band-like or mixed infiltrate. Granulomas and giant cells could be only found in about 30% of the cases. The number of plasma cells was variable accounting for 5-40% of the infiltrate. The number of blood vessels was increased in the majority of the cases. 'Free-floating' collagen bundles surrounded by histiocytes (pseudorosettes) were identified as a new histological feature. An infectious agent could be excluded in all cases. CONCLUSIONS: LPP is a long-standing skin disease, which may also occur in adults and in other body regions than the lower leg. Reproducible clinical and histological criteria allow delineating a diagnostic work-up for LPP.

A new subtype of pachydermodactyly: unilateral pachydermodactyly transgrediens.

Pachydermodactyly describes a rare condition of localized fibromatosis, usually symmetrically affecting the interphalangeal joints of both hands. We describe a case of a new subtype of pachydermodactyly in a 14-year-old boy, which we term 'unilateral pachydermodactyly transgrediens'. This atypical pattern is caused by specific localized mechanical manipulation of the hands. This condition contributes to the completely indolent spectrum of pachydermodactyly, and usually does not need therapy. Therefore it is essential not to misinterpret it as an inflammatory state such as juvenile idiopathic arthritis. The correct diagnosis of pachydermodactyly and its rare subtypes, as we describe in this case, often spares the affected patients unnecessary invasive diagnostic procedures and immunosuppressive therapy.

[Morphological and genetic aspects of Spitz tumors]. / Morphologische und genetische Aspekte bei Spitz-Tumoren.

BACKGROUND: Spitzoid melanocytic neoplasms (i.e. Spitz nevi, atypical Spitz tumors and spitzoid melanoma) are a clinical, histopathological and molecular genetic heterogeneous group of melanocytic skin tumors. OBJECTIVES: Correlation of the histological features of spitzoid neoplasms with molecular genetic aberrations. MATERIAL AND METHODS: A review and summary of the scientific literature. RESULTS: Several histopathological and molecular genetic distinct subtypes of spitzoid lesions have been defined. Epithelioid Spitz tumors commonly show a loss of the BAP1 gene and BRAF mutations and are associated with a hereditary tumor predisposition syndrome. Desmoplastic Spitz tumors frequently harbor HRAS mutations and gains of the chromosome arm 11p. Plexiform Spitz tumors often display ALK translocations. The morphology of Spitz tumors with ROS1, NTRK1, RET and BRAF fusion genes seems to be unspecific and is currently not well characterized. CONCLUSION: Morphological features offer valuable clues to the underlying genetic aberrations in spitzoid neoplasms. Genetic aberrations can be found in the entire biological spectrum of spitzoid neoplasms (i.e. Spitz nevi, atypical Spitz tumors and spitzoid melanoma) and are, therefore, probably not useful for distinguishing benign from malignant tumors; however, genetic aberrations represent important targets for therapeutic interventions and offer investigational treatment options for patients with metastatic disease. The appearance of multiple epithelioid melanocytic tumors with BAP1 loss indicates a hereditary tumor syndrome and warrants genetic counseling and preventive screening of affected individuals.

Fumarate hydratase immunohistochemical staining may help to identify patients with multiple cutaneous and uterine leiomyomatosis (MCUL) and hereditary leiomyomatosis and renal cell cancer (HLRCC) syndrome.

AIMS: Multiple cutaneous and uterine leiomyomatosis (MCUL) also named as hereditary leiomyomatosis and renal cancer syndrome (HLRCC) is an autosomal dominant disorder caused by heterozygotic germline mutations in fumarate hydratase (FH) with incomplete penetrance and clinically challenging to diagnose. To test immunohistochemistry for FH as a potential marker for the detection of FH-deficiency. METHODS AND RESULTS: We have tested 42 smooth muscle neoplasms, 13 lesions of patients with suspicious or confirmed HLRCC, 20 sporadic piloleiomyomas, two angioleiomyomas and 7 leiomyosarcomas. FH staining grades from 1 to 3. Ten of the 13 lesions from the patients with HLRCC syndrome showed negative FH staining. Most sporadic piloleiomyomas presented grade 3 FH staining although five cases presented grade 1 FH staining. Sensitivity of FH staining in our series is 83.3% but specificity is 75%. CONCLUSIONS: This staining could indicate a high risk of HLRCC in most of the confirmed cases but it could also suggest the presence of a syndrome in up to 25% of sporadic cases. HLRCC syndrome should be rule out in FH negative piloleiomyomas after complete anamnesis if multiple lesions or positive familiar history is found.

Herpes simplex virus and cytomegalovirus co-infection presenting as exuberant genital ulcer in a woman infected with human immunodeficiency virus.

In patients infected with human immunodeficiency virus (HIV), genital herpes can result in severe and atypical clinical presentations, and can become resistant to aciclovir treatment. Rarely, these manifestations may represent concurrent herpes simplex virus (HSV) with other agents. We report a 41-year-old black woman with HIV who presented with extensive and painful ulceration of the genitalia. Histological examination of a biopsy sample was suggestive of herpetic infection, and intravenous aciclovir was started, but produced only partial improvement. PCR was performed on the biopsy sample, and both HSV and cytomegalovirus (CMV) DNA was detected. Oral valganciclovir was started with therapeutic success. CMV infection is common in patients infected with HIV, but its presence in mucocutaneous lesions is rarely reported. This case exemplifies the difficulties of diagnosis of genital ulcers in patients infected with HIV. The presence of exuberant and persistent HSV genital ulcers in patients with HIV should also raise suspicions of the presence of co-infection with other organisms such as CMV.

Expression of programmed death-1 (CD279) in primary cutaneous B-cell lymphomas with correlation to lymphoma entities and biological behaviour.

BACKGROUND: Programmed death-1 (PD-1/CD279) is a cell-surface protein expressed in activated T cells and a subset of T lymphocytes including follicular helper T cells (TFH ). The interaction between PD-1 and its ligands plays a role in immune response and evasion of malignancies. In nodal follicular lymphoma, the number of intratumoral PD-1-positive lymphocytes is associated with overall survival. OBJECTIVES: To investigate 28 cases of primary cutaneous B-cell lymphoma, including the subtypes PCFCL (n = 10), PCMZL (n = 10) and DLBCL-LT (n = 8) for the number and density of PD-1-positive cells. METHODS: Immunohistochemical staining and a computerized morphometric analysis for evaluation were applied. The results were correlated with the clinical outcome. To distinguish between activated T cells and TFH we performed PD-1/bcl-6 double staining and compared these results with CXCL-13 staining. Double staining for PD-1 and PAX-5 was used to investigate whether tumour cells were positive for PD-1. RESULTS: The PD-1-positive cells represented tumour-infiltrating T cells (TILs). Only a minor subset was represented by TFH . Patients with DLBCL-LT had a significantly lower number of PD-1-positive TILs than those with PCMZL (P = 0·012) and PCFCL (P = 0·002) or both (P = 0·001). The difference between PCMZL and PCFCL did not reach significance (P = 0·074). The tumour cells were negative for PD-1. CONCLUSIONS: A higher number of PD-1-expressing cells was found in indolent PCMZL and PCFCL than in high-malignant DLBCL-LT. The PD-1-positive cells represented not only TFH , but also other activated T cells as a part of the tumour microenvironment. The tumour cells in all investigated types of PCBCL did not show aberrant PD-1 expression.

Inmunohistoquímica en dermatopatología: revisión de los anticuerpos utilizados con mayor frecuencia (parte II) / Immunohistochemistry in Dermatopathology: A Review of the Most Commonly Used Antibodies (Part II)

La dermatopatología incluye una larga lista de entidades, algunas con una histopatología muy similar. La immunohistoquímica representa una importante herramienta de ayuda en el diagnóstico, diagnóstico diferencial y pronóstico de muchas de las neoplasias cutáneas. La inmunohistoquímica es también la mejor técnica para determinar el origen de un tejido o la diferenciación de las células neoplásicas. En muchos casos, la inmunohistoquímica permite un diagnóstico más preciso de los distintos procesos infiltrando la piel. Este artículo revisa el papel de la inmunohistoquímica en el estudio de la diferenciación y el comportamiento biológico de la mayoría de las neoplasias que pueden afectar a la piel. Se revisan las técnicas de inmunoperoxidasa, se discute la utilidad de los anticuerpos utilizados con mayor frecuencia y se presentan una serie de problemas diagnósticos en los que la immunohistoquímica puede resultar muy útil. En cada caso, la finalidad es llegar a un diagnóstico concreto y definitivo. En esta segunda parte de nuestra revisión se analizan los anticuerpos más útiles y específicos en el estudio de las infecciones cutáneas, así como de las neoplasias epiteliales, musculares, vasculares, linfohematológicas, neurales, neuroendocrinas y melanocíticas afectando a la piel. Al final, se incluye una breve revisión del perfil inmunohistoquímico de las metástasis cutáneas de neoplasias malignas viscerales (AU)

Dermatopathology includes a long list of disorders, some of which have very similar histopathology. Immunohistochemistry is an important auxiliary tool for diagnosis and differential diagnosis, and for predicting the outcome of many skin tumors. It is also the main technique for determining the origin of a tissue or the differentiation of neoplastic cells. In many cases, immunohistochemistry provides a more accurate diagnosis of the different processes that infiltrate the skin. This review examines the role of immunohistochemistry in studying the differentiation and biological behavior of the majority of tumors that can involve the skin. We review immunoperoxidase techniques, discuss the utility of the most commonly used antibodies, and highlight a number of diagnostic problems in which immunohistochemistry may be very useful. In each case, the goal is to reach a specific and definitive diagnosis. In the second part of our review, we examine the most useful and specific antibodies in the study of skin infections and of epithelial, muscular, lymphatic and hematologic, neural, neuroendocrine, and melanocytic neoplasms that affect the skin. Finally, we include a brief review of the immunohistochemical profile of skin metastases of malignant visceral tumors (AU)

Inmunohistoquímica en dermatopatología: revisión de los anticuerpos utilizados con mayor frecuencia (parte I) / Immunohistochemistry in Dermatopathology: A Review of the Most Commonly Used Antibodies (Part I)

La dermatopatología incluye una larga lista de entidades, algunas con una histopatología muy similar. La immunohistoquímica representa una importante herramienta de ayuda en el diagnóstico, diagnóstico diferencial y pronóstico de muchas de las neoplasias cutáneas. La inmunohistoquímica es también la mejor técnica para determinar el origen de un tejido o la diferenciación de las células neoplásicas. En muchos casos la inmunohistoquímica permite un diagnóstico más preciso de los distintos procesos infiltrando la piel. Este artículo revisa el papel de la inmunohistoquímica en el estudio de la diferenciación y el comportamiento biológico de la mayoría de las neoplasias que pueden afectar a la piel. Se revisan las técnicas de inmunoperoxidasa, se discute la utilidad de los anticuerpos utilizados con mayor frecuencia y se presentan una serie de problemas diagnósticos en los que la immunohistoquímica puede resultar muy útil. En cada caso, la finalidad es llegar a un diagnóstico concreto y definitivo. En la primera parte de esta revisión se estudian los anticuerpos que exploran las distintas líneas de diferenciación de las neoplasias cutáneas (AU)

Dermatopathology includes a long list of disorders, some of which have very similar histopathology. Immunohistochemistry is an important auxiliary tool for diagnosis and differential diagnosis, and for predicting the outcome of many skin tumors. It is also the main technique for determining the origin of a tissue or the differentiation of neoplastic cells. In many cases, immunohistochemistry provides a more accurate diagnosis of the different processes that infiltrate the skin. This review examines the role of immunohistochemistry in studying the differentiation and biological behavior of the majority of tumors that can involve the skin. We review the immunoperoxidase techniques, discuss the utility of the most commonly used antibodies, and highlight a number of diagnostic problems in which immunohistochemistry maybe very useful. In each case, the goal is to reach a specific and definitive diagnosis. In the first part of this review, we examine the antibodies that determine the different cell-differentiation profiles of skin tumors (AU)

Immunohistochemistry in dermatopathology: a review of the most commonly used antibodies (part II).

Dermatopathology includes a long list of disorders, some of which have very similar histopathology. Immunohistochemistry is an important auxiliary tool for diagnosis and differential diagnosis, and for predicting the outcome of many skin tumors. It is also the main technique for determining the origin of a tissue or the differentiation of neoplastic cells. In many cases, immunohistochemistry provides a more accurate diagnosis of the different processes that infiltrate the skin. This review examines the role of immunohistochemistry in studying the differentiation and biological behavior of the majority of tumors that can involve the skin. We review immunoperoxidase techniques, discuss the utility of the most commonly used antibodies, and highlight a number of diagnostic problems in which immunohistochemistry may be very useful. In each case, the goal is to reach a specific and definitive diagnosis. In the second part of our review, we examine the most useful and specific antibodies in the study of skin infections and of epithelial, muscular, lymphatic and hematologic, neural, neuroendocrine, and melanocytic neoplasms that affect the skin. Finally, we include a brief review of the immunohistochemical profile of skin metastases of malignant visceral tumors.