Significance of Primary Melanoma Regression on Local Infiltrate and Outcome.

INTRODUCTION: The characteristics and the prognostic value of regression in primary melanomas are controversial. OBJECTIVES: To further characterize "hot" and "cold" tumor's stromas and to investigate the association between dermoscopy, pathology, and the prognostic implications of regression. METHODS: A 14-year-collection-based retrospective analysis was carried out on 40 patients with confirmed regressive melanomas. RESULTS: The extent of regression in dermoscopy was associated with the stage of the regression (P = 0.05) and with the MelanA patterns in histology (P = 0.02). Blue-gray and gray-brown color of the peppering (P = 0.01), and the eccentric, multifocal character of the dermoscopic regression (P = 0.05) were associated with "hot" stromas (CD8+, Granzym B+). Focal histologic regression (regressing melanomas) was associated with a good outcome (P < 0.001), while a complete regression (regressed melanomas) was associated with melanoma-related death (P < 0.001). "Hot" stromas (CD8+ were significantly associated with survival at 10 years (P = 0.044), while "hot" stromas (Granzyme B+) were associated with the locoregional extension (P = 0.016), and the initial distant metastasis (P = 0.016). CONCLUSIONS: Dermoscopic features of regression in primary melanomas were associated with the stage of regression, its extent, and the "hot" or "cold" nature of the tumor stroma, with prognostic implications.

Association of subungual melanoma and subungual squamous cell carcinoma: A case series.

BACKGROUND: Subungual squamous cell carcinoma (SSCC) and subungual melanoma (SUM) are rare tumors. Several case reports of association of SSCC with SUM (SSCC-SUM) have been published. OBJECTIVE: We sought to document the clinical, dermoscopic, and histologic features in a case series of SSCC-SUMs and describe their relative frequency compared with those of SSCC and SUM. METHODS: All patients who underwent surgical exploration of the nail apparatus with a dermatopathologic examination from 2012 to 2015 were reviewed retrospectively to identify all cases of SSCC, SUM, and SSCC-SUM. For patients with SSCC-SUM, clinical characteristics were obtained from electronic medical records. All histologic specimens were reviewed by 3 dermatopathologists. RESULTS: The medical records of 456 patients were reviewed. SSCC was diagnosed in 78 (17%), SUM was diagnosed in 63 (14%), and SSCC-SUM was diagnosed in 9. Patients with SSCC-SUM accounted for 11% of those with a diagnosis of SSCC (9 of 78) and 14% of those with a diagnosis of SUM (9 of 63). LIMITATIONS: This was a single-institution retrospective study. CONCLUSION: The association of SSCC and SUM is relatively frequent in patients with SUM and warrants further consideration to understand the underlying mechanisms involved.

[The key role of the pathologist in the diagnosis of syphilis: A case report]. / L'apport du pathologiste dans le diagnostic de syphilis : à propos d'un cas.

Syphilis is a resurging sexually transmitted infection linked to Treponema Pallidum. Syphilitic lymphadenitis can be present during the 3 stages of the disease. Its histological diagnosis remains challenging for the pathologist given its possible misleading aspect and its ability to mimic as well as reactional as tumoral conditions. We report the case of an HIV-infected young patient referred for suspicion of an aggressive lymphoma. Histological and immunohistochemical analysis of cervical lymphadenopathy revealed secondary syphilis.

Application of C4d Immunohistochemistry on Routinely Processed Tissue Sections for the Diagnosis of Autoimmune Bullous Dermatoses.

The diagnosis of autoimmune bullous dermatoses relies greatly on direct immunofluorescence (DIF) examination performed on frozen tissue sections, showing deposits of immunoglobulins and/or C3 on specific cutaneous structures. However, frozen material is not always available for DIF; therefore, alternative techniques are needed in the diagnostic procedure. We therefore tested the usefulness of C4d immunohistochemistry on formalin-fixed, paraffin-embedded tissue sections for the diagnosis of bullous pemphigoid (BP) and pemphigus (P). A retrospective immunohistochemical study was performed on biopsies of BP (n: 29) and P (n: 22, including 19 Pemphigus vulgaris and 3 paraneoplastic), submitted for routine histological examination and compared with DIF on the corresponding frozen sections. Twenty-five BP biopsies (86.2%) showed C4d deposits seen as a linear labeling along the dermal-epidermal junction and on the membrane of basal keratinocytes. Seventeen P biopsies (77.2%) showed C4d deposits in a classical "intercellular" pattern, predominating on the lower epidermal layers. The sensitivity, specificity, positive predictive value, and negative predictive value reached 86%, 98%, 96%, and 92% in BP, respectively and 77%, 98%, 94%, and 92% in P, respectively. Furthermore, in the cases where serological tests were available, the sensitivity of C4d detection was higher than that of enzyme-linked immunosorbent assay/indirect immunofluorescence in both BP (87% vs. 67%) and P (82% vs. 54.5%). We conclude that DIF on frozen sections still remains the gold standard for the immunopathological diagnosis of BP and P; however, in the absence of frozen material, C4d immunohistochemistry performed on routinely processed biopsy material can be of considerable help in confirming the diagnosis.

[Eosinophilic angiocentric fibrosis and granuloma facial with extra facial presentation, the same pathology?]. / Fibrose angiocentrique à éosinophiles et granulome facial à forme extrafaciale, une même entité ?

Eosinophilic angiocentric fibrosis is a rare fibro inflammatory lesion of unknown etiology which occurs usually in the upper respiratory tract mucosa of middle-aged adults. The histologic features show an eosinophilic vasculitis and an angiocentric fibrosis with onion-skin pattern. Firstly described as a mucosal variant of the granuloma facial, which is a rare cutaneous vasculitis with eosinophils, it is considerated by some authors as separated entities. Four cases have been described in the orbit and three of them were in fact an extension of a sinusal lesion. We report the first case affecting a 69-years-old male patient who showed an isolated orbital involvement in association with granuloma facial, extra facial. This observation illustrates the relationship between these two pathologies and consolidates the first hypothesis of a single disease with cutaneous or mucosal involvement.

The "intraepidermal epithelioma" revisited: immunohistochemical study of the borst-jadassohn phenomenon.

The true nature of the so-called intraepidermal epithelioma of Borst-Jadassohn is poorly understood; whether this represents a distinct tumor or a morphological phenomenon [Borst-Jadassohn phenomenon (BJP)] shared by different entities has been debated. So far, no detailed immunohistochemical studies have been performed to address this issue. The aim of our study was to get further insight into the pathogenesis of the intraepidermal epithelioma of Borst-Jadassohn/BJP. Tumors showing the BJP [mainly clonal seborrheic keratoses (cSK) and clonal Bowen disease (cBD)] were studied and compared with typical (nonclonal) counterparts. Cell nests in cSK, cBD, hidroacanthoma simplex (HS), and porocarcinoma (PC) showed strong expression of epidermal growth factor-receptors (EGF-R), Ki-67, p63, and p53. Cell nests of clonal SK and HS (but not of clonal BD or PC) expressed keratin 5/6. The expression of E-cadherin and the number of CD1a+ Langerhans cells were reduced within the nests of all lesions, whereas melanocytes were increased in all of them. Keratins 7 and 19 were not expressed in any of the lesions. Tumors showing the BJP exhibit some immunohistochemical differences, suggesting that they represent separate entities. However, they all show strong expression of EGF-R within intraepidermal keratinocyte nests, suggesting that the epithelial growth factor pathway plays a role in the development of the BJP.

Porokeratoma (porokeratotic acanthoma): immunohistological study of a new case.

Porokeratoma (porokeratotic acanthoma) is a very recently described tumor-like acanthoma with features of porokeratosis (cornoid lamellation). We report herein a new case of this poorly known lesion that was studied immunohistochemically and discuss briefly its relationship with porokeratosis.

Expression of p63 in cutaneous metastases.

p63 is an oncogene belonging to the p53 gene family. In normal human skin, p63 is expressed by the least-differentiated keratinocytes of the epidermis and its appendages, by myoepithelial cells of sweat glands, and by a wide variety of primary tumors arising therefrom. The expression of p63 by metastatic skin tumors has been more controversial. In this study, we assessed the usefulness of p63 detection in the differential diagnosis between primary and secondary (metastatic) skin tumors. The expression of p63 was studied in 45 cases of cutaneous metastases, mostly of known primary origin, and 94 benign and malignant epithelial primary skin tumors. p63 was expressed by 85 (89%) of 96 primary skin tumors and 5 (11%) of 45 cutaneous metastases. These results suggest that p63 may be a useful adjunct in the diagnosis of skin carcinomas; however, contrary to what has been previously claimed, expression of p63 does not rule out the metastatic origin of a cutaneous carcinoma.

Merkel cell carcinoma in organ-transplant recipients: report of two cases with unusual histological features and literature review.

BACKGROUND: Non-melanoma skin cancers are the commonest malignancies after organ transplantation and are often associated with human papillomavirus (HPV). Merkel cell carcinoma is an uncommon neuroendocrine skin tumor, of which 67 cases have been reported up till now, usually briefly, in organ transplant patients. METHODS: Among a cohort of 2340 organ-transplant recipients, two patients (one renal, one heart) developed cutaneous Merkel cell carcinomas 5 and 12 years of post graft, respectively. These were studied histologically and immunohistochemically, as well as virologically for the presence of HPV. A thorough literature review of all reported cases of Merkel cell carcinoma following solid organ transplantation was performed. RESULTS: Despite a typical immunophenotype, the tumors showed unusual histological features: both were epidermotropic, and one was intermingled with a bowenoid squamous cell carcinoma. Search for HPV by immunohistochemistry and PCR proved negative in both cases. CONCLUSION: In the setting of organ transplantation, Merkel cell carcinoma is much rarer than other non melanoma skin cancers but may show unusual histologic features. HPV do not seem to be involved in its pathogenesis.

Cytogenetic and molecular analysis of 12 cases of primary cutaneous marginal zone lymphomas.

Primary low-grade B-cell lymphomas of the skin are separated into marginal zone and follicle center lymphomas according to the recent World Health Organization-European Organization for Research and Treatment of Cancer classification, with distinct histologic and immunohistochemical profiles. Some cases remain difficult to distinguish. The degree of relationship with their extracutaneous counterparts is currently being investigated on clinical, histologic and molecular grounds. Cytogenetic analysis using fluorescence in situ hybridization was performed on 12 frozen samples of infiltrated skin that had been classified as marginal zone lymphoma (MZL). Chromosomal changes known to be recurrently observed in systemic MZL of the mucosa-associated lymphoid tissue type, and in follicular center lymphoma were analyzed. These included trisomy for chromosomes 3, 7, 12, and 18 as well as t(14;18) IGH/BCL2, t(14;18) IGH/MLT1, and t(11;18) API2/MLT1 translocations. Complementary molecular search of IGH/BCL2 rearrangement using a polymerase chain reaction technique and of API2/MLT1 mRNA expression by reverse transcriptase-polymerase chain reaction were performed. Two cases showed evidence of trisomy 3 at levels varying from 14% to 20% of the analyzed cells. No other chromosomal abnormalities were found with those techniques in the remaining cases. These results demonstrate that known recurrent chromosomal abnormalities rarely occur in primary cutaneous MZLs and suggest the possibility of a variety of initial oncogenic events leading to a common downstream pathway. These data also underline that fluorescence in situ analysis on routine skin punch biopsies represents a reliable tool for the detection of chromosomal changes, but requires consistent dermal infiltration.

Granular-cell basal cell carcinoma of the skin.

Granular cell basal cell carcinoma (GBCC) is a very rare variant of BCC, of which ten cases have been reported in the literature. We describe here a new case of GBCC studied immunohistochemically. The tumor developed on the face of a 71-year old man and showed typical features of GBCC, i.e. a tumor reminiscent of nodular BCC consisting of cells with a granular eosinophilic cytoplasm. Immunohistochemically, tumor cells expressed cytoplasmic reactivity for keratins, CD68 and CD15 antigens, bcl-2 oncoprotein and nuclear reactivity for the p63 protein. Based on a review of the literature, the salient features of GBCC are discussed.

[Pathological and clinical correlations in primary cutaneous B-cell lymphomas: a series of 44 cases]. / Lymphomes B cutanés primitifs: corrélations anatomo-cliniques dans une série de 44 cas.

AIMS: histological and clinical relationship study of 44 cases of primary cutaneous B cell lymphoma, classified according to WHO classification. MATERIALS AND METHODS: histological, immunological and molecular analysis was correlated with clinical data. RESULTS: 33 cases (75%) were marginal zone B-cell lymphomas (MZL), with head and trunk predominance (median age = 54 years). Relapses in other mucosa-related sites occurred in 3 patients. Histological transformation implied a more aggressive treatment in 3 cases. A favorable outcome was observed in most cases. 9 (20%) diffuse large B-cell lymphomas (DLBCL) appeared as a unique nodule, with female predominance (median age = 74 years) and 4 lymphoma-related deaths which seemed age-related (> 70 years) with only one lower limb localization. Histological aggressive features were present in 3 patients with a fatal outcome. 2 (5%) WHO grade 3 follicular lymphomas (FL) had an heterogeneous phenotype, with head localization, cutaneous relapses and good outcome. CONCLUSIONS: MZL, the predominant type, has a good prognosis, although transformation can occur, needing a more aggressive treatment. DLBCL, observed in older patients, has clinical and histological prognostic factors identical to extra-cutaneous lymphomas. FL appears rare and has an heterogeneous phenotype. Relationships with its nodal counterpart remains unclear.

Immunoreactivity of hepatocyte paraffin 1 monoclonal antibody in cutaneous metastatic tumors.

Hepatocyte paraffin 1 (Hep Par 1), a monoclonal antibody recognizing an antigen thought to be specific for hepatocyte mitochondria, is considered the most specific and sensitive marker of normal and neoplastic hepatocytes and has been used in diagnosing hepatocellular carcinomas. Recent data suggest that the specificity of Hep Par 1 for hepatic neoplasms is not absolute; nonhepatic neoplasms might express this marker. We assessed the value of Hep Par 1 in the diagnosis of cutaneous metastases of visceral tumors by immunostaining 65 biopsy or excision specimens with Hep Par 1. Hepatocarcinomas (primary and metastatic to the skin) showed specific (coarse granular intracytoplasmic) immunoreactivity. A similar reactivity pattern was found in 5 of 10 metastases of bronchial adenocarcinoma. Nonspecific (weak, nongranular) cytoplasmic immunoreactivity was observed in 5 cases of nonhepatic skin metastases. Hep Par 1 seems to be a sensitive marker of hepatocellular carcinomas metastatic to the skin, but its specificity is not absolute because it might be expressed in metastases of nonhepatic tumors, namely bronchial adenocarcinomas. Hep Par 1 should be used with caution in the investigation of cutaneous metastases from an unknown primary site, preferably in conjunction with other markers of neoplastic hepatocytes.

Cutaneous necrosis revealing the coexistence of an antiphospholipid syndrome with acquired protein S deficiency, factor V Leiden and hyperhomocysteinemia.

UNLABELLED: We report an exceptional case of cutaneous necrosis due to the coexistence of 4 thrombophilic factors, inherited and acquired. We would like to draw attention to these unrecognized associations. CASE REPORT: A 72-year-old woman was admitted with a 5 month history of necrotic nonhealing, painful ulcer of both legs and recently a purple toe. She had a history of 3 deep venous thromboses of the leg complicated by pulmonary embolism. A skin biopsy of the ulcer and purple toe showed only thrombosis in the dermal vessel. Laboratory findings showed a circulating lupus anticoagulant, positive anticardiolipin antibodies, antinuclear antibodies (1/320 dilution) and an anti Sm. Moreover, activated protein C resistance associated with factor V Leiden mutation and hyperhomocysteinemia was found; protein S was transiently low. With iloprost, oral anticoagulant, vitamin B12 and folic acid, the evolution was good, with healing of ulcer. COMMENTS: cutaneous necrosis can reveal hypercoagulable states, sometimes complex. We find 4 thrombophilic factors in our case, i.e. antiphospholipid antibodies, factor V Leiden, protein S deficiency and hyperhomocysteinemia. This is exceptional but highlights the role of several constitutional and acquired thrombophilic factors in the genesis of thrombosis. Extended protein C pathway disturbances could explain the mechanism that leads to cutaneous necrosis, in this patient, with an antiphospholipid syndrome. This case shows that it is necessary in some circumstances to make a complete hemostatic laboratory search to detect several thrombophilic factors. If they are present they can justify an oral anticoagulant treatment and a familial screening.