[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.

Cutaneous collagenous vasculopathy: ultrastructural and immunohistochemical study of a new case.

Cutaneous collagenous vasculopathy is a very rare entity first described in 2000, manifesting clinically with acquired, progressively diffuse, cutaneous telangiectases with a histologically distinct aspect, characterized by a thick hyaline collagenous wall. Its cause is unknown. Differential diagnosis includes mainly generalized essential telangiectasia and telangiectatic mastocytosis. We report a 65-year-old Caucasian patient who presented with progressive telangiectasia starting over the lower limbs that spread progressively upwards. Histopathologic (light and electron microscopic) examinations were typical of cutaneous collagenous vasculopathy. We review the salient clinicopathologic features of this poorly known condition.

Conversion from calcineurin inhibitors to sirolimus reduces vascularization and thickness of post-transplant cutaneous squamous cell carcinomas.

BACKGROUND: Immunosuppression favors the development of skin cancer. Experimental data suggest that sirolimus (SRL) has antitumoral and antiangiogenic properties. An investigation was undertaken into the effects of SRL on squamous cell carcinoma (SCC) developing in organ transplant recipients (OTR) receiving immunosuppressive treatments, with special emphasis on vascularization. MATERIALS AND METHODS: SCC that developed in eight OTR before and after conversion from calcineurin inhibitors (CNI) to SRL were compared for thickness, differentiation, ulceration, perineural invasion, density of peritumoral infiltrate, peritumoral vascularization, density of T-regulatory cells and of intratumoral Langerhans cells and growth fraction. RESULTS: SCC developing under SRL showed lower peritumoral vascularization and thickness, and higher growth fraction and density of peritumoral T-regulatory cells. CONCLUSION: Conversion from CNI to SRL at clinically relevant doses is associated in vivo with a reduced vascularization and thickness of post-transplant human cutaneous SCC. This effect could account for the beneficial effect of SRL on immunosuppression-induced skin carcinogenesis in humans.

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.

Multinucleate cell angiohistiocytoma: report of three new cases and literature review.

Multinucleate cell angiohistiocytoma (MCA) is a rare benign vascular proliferation of the skin of unknown cause. About 75 cases have been reported previously. We present herein three new cases of MCA studied immunohistologically and present a review the relevant literature that delineates the salient clinicopathological features of this unusual entity.

Granular parakeratosis in a patient treated with liposomal doxorubicin for ovarian carcinoma.

Granular parakeratosis is a rare benign dermatosis caused by an acquired disorder of keratinization that usually manifests with reddish-brown keratotic papules and plaques in intertriginous areas. It has specific histologic features but its pathogenesis remains unclear. Its frequency is probably underestimated because the condition is usually misdiagnosed as simple intertrigo. We report herein a new case of granular parakeratosis in a woman treated with liposomal doxorubicin for ovarian carcinoma that showed complete remission after discontinuation of chemotherapy. The relationship between granular parakeratosis and chemotherapy is discussed.

Clinicopathologic monitoring of the skin and oral mucosa of the first human face allograft: Report on the first eight months.

BACKGROUND: The first human face allograft was performed in France on November 27, 2005. We report herein the clinicopathologic findings from the skin and oral mucosa of this allograft during the first eight months. METHODS: Sequential biopsies were taken from the facial skin (n = 3), oral mucosa (n = 20), and sentinel skin graft (n = 11) from day 3 to day 220 postgraft and examined (immuno)histologically, using a pathological score previously proposed for evaluation of rejection in composite tissue (hand) transplantation. RESULTS: The patient developed clinically rejection episodes at day 20 and during the eighth month postgraft, manifesting with redness and edema of the facial skin, oral mucosa, and sentinel graft skin. Pathologically, changes suggestive of rejection grades 0, I, II, and III were seen in 1, 1, 1, and 0 biopsies of facial skin, 7, 2, 1, and 1 biopsies of sentinel skin graft and 3, 5, 8, and 4 biopsies of oral mucosa, respectively. Pathological changes were generally more severe in the oral mucosa than in facial and sentinel graft skin (mean scores 1.85, 0.64, and 1, respectively). CONCLUSIONS: As it happens with other composite tissue allografts, close clinicopathologic monitoring of the skin (and oral mucosa) seems to be the most reliable way to detect rejection in the setting of human facial tissue allotransplantation. Apart from these rejection episodes, the skin and mucosa maintained a normal microscopic structure, paralleling functional recovery.

Subsequent skin cancers in kidney and heart transplant recipients after the first squamous cell carcinoma.

BACKGROUND: The increased incidence of skin cancers in transplant patients is well documented; however, few data exist on the risk of subsequent skin tumors in a given patient after the first skin cancer. The aim of this study was to compare the individual rate of subsequent skin cancers in kidney (KTR) and heart transplant recipients (HTR) after the first squamous cell carcinoma (SCC) and to assess risk factors for tumor multiplicity. METHODS: In all, 188 patients (121 KTR/67 HTR) were studied for up to 5 years. The cumulative number of SCC, basal cell carcinomas, Bowen's diseases, premalignant keratoses, and keratoacanthomas was recorded yearly after the first SCC. RESULTS: Overall, 71% of patients developed 757 new skin tumors. At 5 years, 100% of HTR and 88% of KTR had presented new tumors. However, the mean number of all tumors was significantly higher in KTR (3.4 vs. 2.0, 4.8 vs. 2.6, 6.6 vs. 2.9, 8.5 vs. 3.5, and 9.7 vs. 4.6 at 1, 2, 3, 4, and 5 years, respectively). Transplantation before 1984, multiple tumors at first consultation, eye and hair color, and skin type were predictive of multiple tumors. Early minimization of immunosuppression and of sun exposure tended to be associated with a reduced rate of all tumors and of SCC, respectively. CONCLUSIONS: Although the proportion of HTR developing new tumors is greater as compared with KTR, the mean number of tumors per patient is higher in KTR. This could be due to a longer immunosuppression in patients younger at transplantation.

Pathological score for the evaluation of allograft rejection in human hand (composite tissue) allotransplantation.

The experience obtained from the human hand allografts (HHA) performed to date suggests that the skin is a priviledged target of allograft rejection in this setting. The aim of this study was to establish a pathological score for assessing the severity of HHA rejection. The pathological slides of 89 skin biopsies obtained from the allografted limbs of six HHA recipients from day 0 to 5 years post-graft were retrospectively examined. According to the severity of the pathological changes observed, the following grades of rejection are proposed: 0: no rejection, I: mild rejection, II: moderate rejection, III: severe rejection, IV: very severe rejection. This grading system can be used as a basis for monitoring allograft rejection and for assessing the effects of the immunosuppressive treatment aiming at reversing HHA rejection; it can also be used for monitoring rejection of other skin-containing CTA.

[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.

No recurrence of posttransplantation Kaposi's sarcoma three years after renal retransplantation.

Kaposi's sarcoma (KS) develops in 0.5-5% of organ transplant patients; it usually regresses upon treatment reduction, but this may result in graft loss necessitating return to dialysis and/or retransplantation. Until now posttransplantation KS is considered to recur upon reintroduction of immunosuppressive treatment, a fact that has limited retransplantation of patients with previous KS. We report a patient with posttransplantation KS who received a second renal transplantation after having been off immunosuppressive treatment for 10 years, in whom KS has not recurred more than 3 years after retransplantation. This unique observation suggests that retransplantation of patients with previous posttransplantation KS is possible.

Clinicopathologic features of graft rejection of the first human hand allograft.

BACKGROUND: The first human hand allograft, performed in Lyon, France, on September 23, 1998, was removed during month 29 posttransplantation as the result of rejection because the patient did not comply with the immunosuppressive treatment. METHODS: The patient was regularly examined from the day of transplantation to amputation. Biopsies were taken from the skin of the allograft and examined immunohistologically. After amputation, various tissue specimens obtained from the allograft (including skin, tendons, bone, muscles, and joints) were studied. RESULTS: From month 15 onward, the allografted skin presented lichenoid papules that progressively spread and coalesced into diffuse erythematous-scaly lesions over the allografted hand. Histologically, these showed an aspect of chronic lichenoid cutaneous graft-versus-host disease. At the time of amputation, erosive and necrotic areas over the skin were present. Pathologic examination of the allograft showed that the most severe changes were found in the skin. Mild inflammation was found in muscles and tendons. Bones (including bone marrow) and joints were spared. CONCLUSIONS: The skin is the main target of rejection in human hand allografts. Close clinicopathologic monitoring of the skin is the most reliable way to detect rejection in human composite tissue allografts.

Novel biological immunotherapies for psoriasis.

Psoriasis is a common skin disease affecting 1 - 3% of the white population. Although its physiopathogenesis still remains poorly understood, recent data suggest a key role played by memory T cells in the genesis of skin and joint lesions. Recent developments in the understanding of cellular mechanisms underlying psoriasis and in biotechnologies have given rise to a generation of biological agents that have shown clinical efficacy in treating psoriasis. These agents, including chimeric antibodies, fusion proteins and recombinant interleukins, specifically target the activated memory T cells directly involved in the development of psoriasis lesions and inhibit their action either directly or through inhibition of pro-inflammatory cytokines. Compared with conventional systemic treatments, they show a better safety profile and allow durable remissions. Some of these agents were very recently marketed for the treatment of psoriasis and hopefully others will follow. These biologicals have opened a new era for the management of this disease; they are reviewed in this article, based on data available in the literature.

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.

Basal cell carcinomas developing in solid organ transplant recipients: clinicopathologic study of 176 cases.

OBJECTIVE: To assess the clinicopathologic features of basal cell carcinomas developing in organ transplant recipients. DESIGN: Case series. SETTING: University department of dermatology. PATIENTS: One hundred forty-six (7.2%) of 2029 transplant recipients followed up in our department who developed 176 histologically proven basal cell carcinomas. One hundred fifty-three random samples of basal cell carcinomas excised from nonimmunosuppressed patients served as controls. MAIN OUTCOME MEASURES: Clinical data were gathered from the medical records. Histologic slides were retrospectively reexamined. RESULTS: Basal cell carcinomas developed an average of 6.9 years after transplantation, sooner after heart than kidney transplantation, and showed a relative predilection for heart allograft recipients. The mean age of transplant recipients with basal cell carcinomas was significantly lower than that of controls (54.6 vs 69.8 years), especially for recipients of renal transplants, and a male preponderance was found (male-female ratio, 4.8:1 vs 1.3:1). In both groups, basal cell carcinomas were predominantly found on the head and neck, but extracephalic locations were significantly more frequent in transplant recipients (37.5%) than controls (24.5%). Histologically, superficial basal cell carcinomas were more frequent in transplant recipients than controls (33.6% vs 14.4%). The density of the peritumoral cell infiltrate was lower in tumors from transplant recipients compared with controls. The tumor thickness and the presence of epidermal ulceration did not differ significantly between the 2 groups. CONCLUSIONS: Basal cell carcinomas in transplant recipients show some clinicopathologic differences from their "ordinary" counterparts, namely, a younger age at development, male preponderance, more frequent distribution in extracephalic sites, and higher frequency of superficial subtypes.

Clinical quiz. Rubinstein-Taybi syndrome (synonyms: broad thumbs and great toes, characteristic facies, and mental retardation -- broad thumb-hallux syndrome).

A 28-year-old mentally retarded, institutionalised woman was referred to us for evaluation of multiple plantar warts and ingrown nails of both great toes. The patient was born to unrelated parents of North African origin and had one brother and three half-brothers, all of whom were healthy. Physical examination revealed short stature, slight obesity, facial abnormalities (Fig. 1), short and broad thumbs and big toes (Figs. 2 and 3). A keloid was found on the right forearm, that had developed after surgical correction of a fracture (Fig. 4). Ill-defined hyperpigmented macules were observed on the trunk. The patient also presented pruritic eczematous lesions of the limbs and the back that had been present for some years and were recurrent despite treatment with emollients and local steroids. Androgenetic-type alopecia of moderate severity was seen on the vertex of the scalp. Past medical history included polydactylism of the feet and clinodactyly of the thumbs (both corrected surgically), respiratory tract infections, Wolf-Parkinson-White syndrome and refractive errors necessitating glasses.

[Cutaneous tumors in organ transplant recipients]. / Tumeurs cutanées chez les greffés d'organe.

THE CONTEXT: With the improvement in transplant in surgery, organ storage techniques and immunosuppressive treatments, the number of organ transplant recipients is regularly increasing. To preserve the activity of the graft, immunosuppressive treatment is required for life in most cases, leading to prolonged immunodeficiency. These patients exhibit an increased risk of cancer, notably of tumors associated with viruses such as carcinomas, Kaposi's sarcoma and lymphomas. THE DIFFERENT CANCERS CONCERNED: Cutaneous cancers, notably squamous cell carcinomas, are the predominant cancers encountered in transplant recipients and affect around half of the patients within 20 years following the transplant. Squamous cell carcinomas tend to be multiple, may be life-threatening, and appear to predict the onset of other cancers. Exposure to UV, immunosuppression, the relatively old age at the time of the transplant, light skinned phototype, genetic factors and papillomavirus infections are all factors of risk. Other photo-induced tumors, such as melanoma, some sarcomas or Merkel cell carcinomas also appear increased and of severe prognosis. MEASURES OF PREVENTION: The prevalence of these tumors could be reduced by educating the patients on strict sun-protection measures following the transplant. The factors enhancing Kaposi's sarcoma associated with the HHV8 virus remain to be defined. The possibility of transmission of the infection through the graft must lead to the systematic search for this virus in the donors.