Failure of isotretinoin and interferon-alpha combination therapy for HPV-linked severe vulvar dysplasia. A report of two cases.

BACKGROUND: Retinoids (RA) and interferon (IFN) have been reported to be active against a variety of tumors and human papillomavirus (HPV)-related lesions. Because chronic and recurrent HPV-linked vulvar intraepithelial neoplasia 3 (VIN 3) have a high risk of invasion, we evaluated combined therapy of IFN-alpha with 13-cis-retinoic acid (13 cRA) in the treatment of two VIN 3 cases of this type. CASE: Two patients with chronic and recurrent VIN 3 were treated with combined therapy of IFN-alpha (4.5 x 10(6) five times a week) and 13 cRA (1 mg/kg/d) for six months. Clinical regression was observed at the end of treatment in both cases, but histologic features of VIN 3 were still present. CONCLUSION: These data demonstrate the ineffectiveness of the combined regimen of IFN-alpha and 13 cRA with this schedule for a period of six months in recurrent and chronic VIN 3.

Lack of evidence of human herpesvirus 8 DNA sequences in HIV-negative patients with various lymphoproliferative disorders of the skin.

Human herpesvirus 8 (HHV-8) is a new virus which has been reported in Kaposi's sarcoma and some lymphoproliferative disorders such as Castleman's disease and body-cavity-based lymphoma. Because HHV-8 shares homology with Epstein-Barr virus (EBV), we searched for the presence of HHV-8 DNA sequences in various cutaneous T- and B-cell lymphoma by the polymerase chain reaction (PCR). Forty-seven HIV-negative patients with cutaneous lymphoma or large plaque parapsoriasis were enrolled in the study. For the detection of HHV-8 DNA sequences we used PCR followed by a hybridization with a digoxigenin-labelled probe and nested-PCR. HHV-8 DNA sequences could only be detected in a patient with large plaque parapsoriasis. Our study does not suggest any direct implication of HHV-8 in the pathogenesis of most cutaneous lymphoma. Serological studies will be helpful to appreciate if there is an epidemiological link between HHV-8 and cutaneous lymphomas.

An extract from cultured human keratinocytes that contains the major autoantigens related to autoimmune bullous skin diseases.

Autoantibodies characteristic of autoimmune bullous skin diseases (AIBDs) can be detected by immunoblotting on epidermal, dermal, or bovine muzzle extracts. However, none of those substrates contain all the autoantigens involved in AIBDs, and the diagnosis requires the use of various substrates. Human keratinocytes were cultured under such conditions that they expressed the major autoantigens associated with AIBDs. Forty-two sera with antiepidermal antibodies were immunoblotted on the keratinocyte extract. Bands corresponding to desmoglein III, desmoglein I, BPAg2, BPAg1, and type VII collagen were found in 38 sera. Desmoplakins I and II were revealed by specific monoclonal antibodies. A review of the patients' charts showed a perfect correlation between the blots and the diagnoses of pemphigus vulgaris, pemphigus foliaceus, bullous pemphigoid, cicatricial pemphigoid, and epidermolysis bullosa acquisita. Four sera revealing no band typical of AIBD were from patients with no autoimmune skin disease. Therefore, a single extract of keratinocytes can be used for the differential diagnosis of AIBDs.

Anetoderma of Jadassohn-Pellizzari.

Anetoderma (derived from the Greek anetos, meaning slack) is a term used to describe localized increased laxity of the skin with herniation or outpouching, resulting from abnormal dermal elastic tissue. Primary anetoderma is distinctly rare. We describe a case where we suspect an auto-immune aetiology.

Primary cutaneous medium and large cell lymphomas other than mycosis fungoides. An immunohistological and follow-up study on 54 cases. French Study Group for Cutaneous Lymphomas.

Primary cutaneous medium and large cell lymphomas (MLCL) other than mycosis fungoides (MF) are rare, and their prognosis and treatment are controversial. The clinical, immunohistological and follow-up data of 54 well-documented cases of primary cutaneous MLCL other than MF, seen in our institutions over a 14-year period, were retrospectively reviewed, in order to determine the prognostic factors related to these lymphomas, and to analyse the results obtained with different treatment regimens. Forty-six patients presented with a solitary tumour or with localized lesions, and eight had disseminated cutaneous lesions. According to the updated Kiel classification, 45 cases (83%) corresponded to B-cell lymphomas: centroblastic lymphomas, 32 cases; centroblastic-centrocytic lymphomas, 11 cases; immunoblastic lymphomas, two cases. Nine cases (17%) were classified as T-cell lymphomas: pleomorphic medium and large cell lymphomas, eight cases; anaplastic large cell lymphoma, one case. Four of eight patients with disseminated skin lesions had a T-cell lymphoma, whereas 41 of 46 patients with a solitary tumour had a B-cell lymphoma. Patients with disseminated skin lesions and elevated serum lactate dehydrogenase (LDH) levels had a poor prognosis. Comparison of patients' overall survival, depending on immunohistological subtype, showed that the median survival of patients with pleomorphic T-cell lymphoma was 2.5 years, whereas it was not reached at 12 years for patients with centroblastic-centrocytic and centroblastic lymphoma. The eight patients with disseminated skin lesions were treated with polychemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Herpesvirus-like DNA sequences in patients with Mediterranean Kaposi's sarcoma.

DNA sequences closely related to herpesvirus-like sequences have been found in AIDS-associated Kaposi's sarcoma. Using PCR, we found herpesvirus-like DNA sequences in Kaposi's lesions and normal adjacent skin in five patients with Mediterranean Kaposi's sarcoma. We did not find these sequences in tissues from patients without Kaposi's sarcoma. Semi-quantitative PCR revealed many more herpesvirus-like sequences in Kaposi's lesions than in unaffected skin. Our results reinforce the hypothesis that an infectious agent closely related to gamma-herpesvirus is implicated in the pathogenesis of Mediterranean and AIDS-associated Kaposi's sarcoma.

Immunophenotype analysis of dendritic cells and lymphocytes associated with cutaneous malignant melanomas.

The purpose of this study was to investigate the relationship between changes in density and distribution of dendritic cells, both in epidermis and in peritumoral infiltrate, and lymphocyte subset variations in malignant melanomas (MM) of patients belonging to different risk groups. The collective immunoreactive expression of six markers (S100 protein, CD1-a, HLA-DR, CD4, CD8 and CD25) was analyzed in 13 cutaneous malignant melanomas. Changes were observed in density and distribution of Langerhans cells (LC) (S100+, CD1-a+) in the epidermis overlying the tumor, as well as in peritumoral and intratumoral locations, independently of the tumor-invasion level. A decrease was recorded in LC (S100+, CD1-a+) in the epidermis overlying six tumors, whereas most of the MM studied showed an increase of LC (S100+, CD1-a+) in peritumoral infiltrate. The expression of HLA-DR in tumor cells was controversial; it was observed in three moderate-risk MM, but it was negative in high-risk tumors. The percentage of CD4+ cells was in most cases greater than that of CD8+ in the peritumoral infiltrate, irrespective of the degree of histopathological malignancy. The concomitant expression of the lymphocytic activation marker CD25 (receptor for interleukin 2) in lymphocytic infiltrate was variable. Peritumoral infiltrate in three high risk MM contained few CD25+ cells, and a concomitant decrease was recorded in LC. This preliminary report shows that alterations in the density and distribution of LC may be responsible for determining the degree or T lymphocyte activation, and this may be critical for the development of effective tumor-directed immunity. Further studies are required to demonstrate these hypothetical interrelations.

[Cutaneous ulcerations in sarcoidosis]. / Ulcérations cutanées au cours d'une sarcoïdose.

We report the case of a 23 year-old Caribbean woman with sarcoidosis who developed specific skin ulcerations. Ulcerative lesions in sarcoidosis are distinctly unusual, generally multiple, painless, with preponderant location on the lower limbs. The diagnosis is difficult. The pathogenesis is discussed. The most successful therapy is hydrochloroquine with corticosteroids.

[Proteus syndrome. 8 cases]. / Syndrome Protée: huit cas.

INTRODUCTION: Proteus syndrome most often includes: corporal hemi-hypertrophia, gigantism of the extremities with hyperplasia of the palms and soles, vascular abnormalities and varied types of other hamartomatous tumours. The dysmorphic growth generates functional orthopaedic and orthognatic disabilities that increase with age. OBSERVATIONS: We report, on eight cases, our experience in management of Proteus syndrome abnormalities and the benefits of new techniques in imaging and interventional vascular radiology. The correction of limb orthopaedic abnormalities is complicated with elephantiasic enlargement of soft tissues. In some patients the absence of a deep venous network contra-indicates transcutaneous occlusion of dysplatic vessels. Facial asymmetry and orthognatic anomalies are better managed after permanent teeth have appeared. COMMENTARIES: The management of these disabilities is carried out by staff of different specialities but should be organized by a practitioner who regularly follows the child and detects early the functional disturbances. Aesthetic corrections are performed later.

[Multifocal epithelioid hemangioendothelioma with partial remission after interferon alfa-2a treatment]. / Hémangioendothéliome épithélioïde multifocal en rémission partielle sous traitement par interféron alpha 2a.

INTRODUCTION: Epithelioid hemangioendothelioma (EHE) is a rare vascular tumour of the soft tissue having an intermediate malignancy. Cutaneous presentations have exceptionally been reported. OBSERVATION: A young woman, initially affected by an EHE with cutaneous and bone involvement, then with pulmonary and hepatic localizations, was in partial remission after one year of treatment with alpha 2a interferon. DISCUSSION: In a critical review of the literature, we describe the main features of this tumour and the difficulties to classify this entity in the vascular tumors' spectrum. Histologically, epithelioid hemangioendothelioma has a very characteristic appearance and is clearly different from other vascular tumors as angiolymphoid hyperplasia with eosinophilia and Kimura's disease. The assumption of a multicentric or a metastatic origin when multiple tumor deposits are found, is still not elucidated. Different therapeutic approaches are proposed: surgery, interferon, interleukin-2, retinoids. Randomized studies would be necessary to confirm our results with alpha 2a interferon but are probably difficult to realize because of the lack of cases.

Nonepidermotropic cutaneous lymphomas. A histopathological and immunohistological study of 52 cases.

We report the detailed histological and immunohistological findings in 52 cases of nonepidermotropic cutaneous lymphoma, as revealed by cutaneous lesions. The patients presented mainly with cutaneous nodules and, more rarely, with infiltrated plaques, annular erythema, or erythroderma. The staging procedure following the diagnosis revealed lymph node and/or bone marrow involvement in half of the cases. Nearly 60% of the nonepidermotropic cutaneous lymphomas were of the large-cell type. The reticular dermis was involved in all of the cases, and the papillary dermis was involved in only 11 of them. Nonepidermotropic cutaneous lymphomas were of the B-cell, T-cell, and non-B-, non-T-cell type in 38, 13, and 1 case(s), respectively. A monotypic immunoglobulin light chain expression was detected in 33 of 35 tested cases of the B-cell lymphomas, and a loss of one or several pan-T-cell antigens was observed in all of the cases of the T-cell lymphomas. In seven cases (13%), the diagnosis of malignancy was based only on these immunohistological criteria. This study shows that nonepidermotropic cutaneous lymphomas are B-cell lymphomas in 75% of the cases, most often of the large-cell type. It also emphasizes the value of immunohistochemistry to firmly establish malignancy when routine light microscopical findings are questionable.

[Bowen's disease and bowenoid papulosis: comparative clinical, viral, and disease progression aspects]. / Maladie de Bowen et papulose bowénoïde: données cliniques, virologiques et évolutives comparatives.

Among the VIN (vulvar intraepithelial neoplasia), it is necessary to distinguish the classical Bowen's disease (CBD) and bowenoid papulosis (BP). This retrospective study concerning 75 VIN (36 CBD and 39 BP) demonstrated that the most efficient criteria are the clinical aspect and the age of the onset (CBD = 55.6 years old; BP = 33.2 years old). BP is clinically related to genital warts (41 cases). They share the same age of onset, the fact to be sexually transmitted diseases and the benign evolution. Although virological results between CBD and BP are very similar (human papilloma virus type 16, 18, 31, 33), the development of an invasive carcinoma is mostly related to the CBD (27.8%) and is exceptional in the BP (2.6%).

[Demyelinating nervous lesions in myalgia-eosinophilia syndrome induced by L Tryptophan]. / Lésions nerveuses démyélinisantes au cours du syndrome myalgies-éosinophilie secondaire à la prise de L-tryptophane.

A case of severe peripheral nerve lesions in a patient with eosinophilia-myalgia syndrome induced by L-Tryptophan is reported. Both superficial radial nerves were very tender on palpation. Biopsy of the radial nerve showed myelin abnormalities of the type observed in experimental chronic nerve entrapment. Nerve lesions included asymmetrical distortion of the myelin sheath, segmental demyelination, axonal degeneration and regeneration. Such abnormalities suggest that mechanical factors, presumably due to proliferation of connective tissue, play a role in the nerve lesions observed in this patient.