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Previous studies have reported that repeated solar and artificial UVB (280–320 nm) and UVA (320–400 nm) exposures can modify acquired melanocytic nevi (AMN). We therefore investigated the clinical, dermoscopic, histological and immunohistochemical changes in AMN exposed to UVB and UVA radiation. Twenty healthy volunteers with at least three AMN on the trunk were enrolled in the present study and randomized into two groups to receive equally effective doses of narrow-band (NB)-UVB or UVA1. Three exposures per week were delivered for a total of 4 weeks. During exposures, one AMN was left unprotected, a second one was shielded with an opaque adhesive tape and the third nevus was covered with a commercial sunscreen. After the irradiation cycle, the AMN were surgically removed and underwent histological and immunohistochemical assessment of melanocyte/melanogenesis-related proteins (MART-1, tyrosinase, HMB-45), cell cycle activation markers (Ki-67, topoisomerase IIalpha, p53, Cdk2) and transcription factors (microphthalmia-associated transcription factor, STAT3). Nevi that were exposed to NB-UVB or UVA1 also showed statistically significant increase in size and changes in their dermoscopic features, including overall darkening, increased pigment network expression, formation of branched streaks, and increased number and size of brown globules and dots. AMN that had been covered with opaque tape or sunscreen did not show changes in size or dermoscopic features following UVA1 or NB-UVB exposure. Histological and immunohistochemical analysis did not show any significant change in exposed AMN in comparison with AMN shielded with an opaque adhesive tape or covered with the sunscreen.

Merkel cell carcinoma (MCC) is a skin cancer of neuroendocrine origin that occurs most often in sun-exposed areas. In the general population, it is a disease of older adults, with only 5% of cases occurring below the age of 50 years. Immunosuppression is the significant risk factor for the development of MCC and recently it was suggested that individuals with HIV have a relative risk of 13.4 to developed MCC in comparison with the general population. We report a case of MCC in an HIV-infected patient and we review nine patients with HIV with MCC. Our patient was a 54-year-old man who came to our attention without a known HIV diagnosis. He was apparently in good health and had no risk factor for HIV, but by the atypical site of the lesion and by the relative young age of the patient we suspected a case of immunosuppression and for this reason we did HIV test that had a positive result. The patient was treated with surgery and chemotherapy but died as a result of liver metastases 25 months after his tumor was diagnosed.

Classically, dermatofibrosarcoma protuberans (DFSP) is a disease of adults. The world literature revision shows that several pediatric cases have been reported so far; this might suggest that the number of infants with the condition might be larger than that estimated previously. Here, we report the 183rd case of histologically confirmed DFSP in young age. A 14-year-old white male patient came under our care for a slowly growing, pale brownish lesion on the neck skin. A biopsy specimen showed a DFSP. Subsequently, a wide surgery excision with 3 cm of resection margins including the underlying fascia was performed. To date, the patient has been in follow-up for 6 years without evidence of recurrent disease. The clinical features and treatment of DFSP diagnosed in childhood and adolescence reported in the published literature are reviewed to provide new insights about this rare entity. The aim is to emphasize the importance of biopsy for histologic evaluation in the cases that show a persistent or a large cutaneous plaque or nodule without pathognomonic clinical features that permit a clinical diagnosis. An accurate knowledge of the disease is the prerequisite for a wider recognition and appropriate treatment.

The proliferative activity of the haematopoietic and plasma cells in bone marrow was evaluated under normal and neoplastic conditions, by means of a sequential double immunostaining technique, using monoclonal antibody MIB-1 recognizing the cell proliferation-associated nuclear antigen Ki-67, and antibodies against glycophorin-C, myeloperoxidase, factor VIII-related antigen, and immunoglobulin light chains. Fifty-eight B5 fixed, paraffin-embedded bone marrow biopsies were analysed, including 11 normal controls. 10 cases of myelodysplasia, 14 cases of chronic myeloproliferative disorder, eight cases of acute non-lymphoid leukaemia, and 15 cases of myeloma. In normal marrows, the highest proliferative activity was noticed in the erythroid cells (75% to 95%; mean 90%), in comparison with myeloid precursors (15% to 80%; mean 38%), and megakaryocytes (10% to 20%; mean 14%): no Ki-67 positive plasma cells were found. In all investigated haematological disorders, the expression of MIB-1 by erythroid cells was similar to that observed in controls. Similarly, the percentage of MIB-1 + myeloid precursors in chronic myeloproliferative disorders and myelodysplasia largely overlapped the values observed in normals, and comparable values were also found in the blast cells from acute non-lymphoid leukaemia type M1 and M2. These findings suggest that the evaluation of either erythroid or myeloid proliferative activity is of little value in the differential diagnosis between these myeloproliferative disorders. By contrast, the obvious increase of Ki-67 expression of megakaryocytes in chronic myeloproliferative disorders, with labelling also of micro-megakaryocytes, might sustain the diagnosis in controversial cases. Since cases of mature myeloma showed less than 2% of Ki-67 positive cells, evaluation of proliferative activity is of no value in the differential diagnosis with reactive plasmacytosis. The sequential double immunophenotyping for Ki-67 antigen and for haematopoietic cell lineage-associated markers can be applied in a consistent manner to routine bone marrow biopsies to evaluate proliferating cells in normal and neoplastic conditions.

Author(s): Manganoni, AM; Facchetti, F; Gavazzoni, F; Farisoglio, C; Manca, G; Sereni, E; Marocolo, D; Calzavara-Pinton, PG

Twenty-five elderly patients with oligoblastic acute myeloid leukemia (AML) received subcutaneous granulocyte colony-stimulating factor (filgrastim) in addition to supportive care. Ninety-two percent of the patients had multilineage dysplasia, 17% hypoplasia, and 48% a high-risk karyotype. During filgrastim treatment neutrophil and platelet counts increased significantly (p

CD15 is a useful immunohistochemical marker to identify Reed-Sternberg cells in classical Hodgkin's lymphoma (HL) and to distinguish it from HD-like neoplasms, but data from the literature concerning its expression in HL are quite variable. Using immunohistochemistry we compared the reactivity of three different anti-CD15 clones (MMA, C3D1 and BY87) and found that anti-CD15 MMA clone is a superior reagent in identifying atypical cells, detecting more numerous cells in 28.2%, and being the only positive marker in 12.8% of cases. We conclude that it is advisable to include this reagent in diagnostic immunohistochemical panels.

We evaluated the incidence, morphology, and immunophenotype of intraepidermal collections of mononuclear cells (ICMC) in a large number of inflammatory dermatosis and cutaneous lymphomas. ICMC appeared as small to large aggregates of cells, showing a morphology variable from monocytes to obvious dendritic cells, admixed with rare lymphocytes. ICMC were recognized in the epidermis or within hair follicle epithelium, and were either loosely or compactly arranged. ICMC were identified in 124 of 1,248 skin biopsies (9.9%) of inflammatory or lymphoid infiltrates, and were particularly frequent in spongiotic (43.4%) and in lichenoid dermatitis (10%), whereas they were rarely found in nonspecific superficial dermatitis (3.8%) and in psoriasis (4.7%). ICMC were also frequent in cutaneous T-cell lymphoma (13.3%), where they mimicked Pautrier abscesses. The ICMC forming cells showed a unique phenotype: the majority of them expressed CD1a and S-100, and lacked CD14, similar to mature Langerhans cells, but they were also strongly labeled by anti-CD11b, anti-CD36, and anti-CD68. Moreover, a subpopulation of them expressed CD83, an antigen that is usually absent on Langerhans cells. The occurrence of ICMC is a rather frequent, although hitherto poorly studied, phenomenon, occurring in several dermatosis, but particularly frequent in spongiosis-associated skin reactions. The cells within ICMC are represented by dendritic cells and dendritic cell precursors, whose phenotype indicates their derivation from circulating monocytes and differentiation into mature Langerhans cells.

AIMS: Recombinant alpha-interferon (r-IFN) is an effective therapy for chronic myeloid leukaemia (CML), inducing haematological and major cytogenetic response in 70% and 30% of patients, respectively. In this study we have evaluated the significance of bone marrow (BM) histology on the subsequent response to r-IFN therapy, as well as the morphological changes induced by r-IFN within BM. METHODS AND RESULTS: 73 BM biopsies were studied from 21 patients with Ph1-positive CML in chronic phase at diagnosis and at different times during r-IFN treatment. At diagnosis the probability of achieving a major or complete cytogenetic response was significantly higher in patients with a total marrow cellularity lower than 90% (P = 0.02). During therapy with r-IFN, significant BM changes included disappearance of the CML pattern (P = 0.0002), reduction of M:E ratio (P = 0.0009) and total cellularity (P = 0.0027), and increase in number of terminal megakaryocytes (P = 0.0009) and of fatty tissue regeneration (P = 0.037); only after long-term therapy (mean 20 months), did reticulin fibrosis increase significantly (P = 0.032). CONCLUSIONS: The overall BM morphology in response to treatment displayed different pictures, ranging from persistence of CML (25 biopsies out of 51), to reversion to normal histology (14 out of 51). Persistence of diffuse morphological abnormalities was associated with lack of cytogenetic responsiveness (P = 0.025).

A case of acute inflammatory myopathy associated with the use of pravastatin, a new hydrophilic 3-hydroxy-3 methylglutaril coenzyme A reductase inhibitor, is reported. The patient, a 69-year-old man was affected by non-insulin-dependent diabetes mellitus and hypertension. He assumed pravastatin (20 mg/day) because of hypercholesterolemia. He was admitted with acute myopathy of the lower limbs which resolved in a few days after pravastatin discontinuation. A previously unknown hypothyroidism, probably due to chronic autoimmune thyroiditis, was evidenced. Muscle biopsy (left gastrocnemius) revealed a perimysial and endomysial inflammatory infiltrate with a prevalence of CD4+ lymphocytes. While lovastatin and simvastatin have been associated with toxic myopathy, pravastatin-associated myopathy could represent a distinct, inflammatory entity.

The use of vein or muscle grafts to bridge nerve defects longer than 1-1.5 cm gives poor results. Veins collapse and in muscle grafts axons may regrow outside the graft. We used veins (to guide regeneration) filled with muscle (to avoid vein collapse). Nerve regeneration through 1 and 2 cm grafts made of vein plus muscle was compared with similarly long traditional nerve grafts, free fresh muscle grafts, and empty vein grafts. Regeneration was assessed clinically and histologically (qualitative and quantitative evaluation) in the graft and distal nerve stumps. Vein plus muscle grafts were superior to vein and fresh muscle grafts both functionally and histologically. Functional results were similar to those found in traditional nerve grafts, but axon number was superior in the veins filled with muscle. This suggests that vein filled with muscle might serve as a grafting conduit for the repair of peripheral nerve injuries and could give better results than traditional nerve grafting. © 1993 Wiley-Liss Inc.

Little is known about the nature of the large intrasinusoidal cells exhibiting cytophagocytosis, which are the histologic hallmark of sinus histiocytosis with massive lymphadenopathy (SHML) (Rosai-Dorfman disease). Using a broad panel of monoclonal and polyclonal antibodies, we analyzed the immunophenotype of the cell infiltrates in seven lymph node biopsy specimens from five cases of SHML. The SHML cells constantly expressed the S-100 protein, concanavalin agglutinin and peanut agglutinin lectins, and monocyte-macrophage-associated antigens CD 11c, CD 14, CD 33, CD 68, and LN 5. Labeling with other antimacrophage antibodies was extremely variable, with some (MAC 387, lysozyme) restricted to clusters of SHML cells and others (CD 11b, CD 36, alpha-1-antichymotrypsin) staining only sscattered cells. The CD 1a antigen was found on some cells in only one case, whereas HLA-DR and the HLA-DR-associated invariant chains were absent. The heterogeneity of SHML cell marker expression might be related to the local content of factors (eg, cytokines) capable of modulating the phenotype of monocytes and derived cells. All cases presented with huge amounts of medium-sized mononuclear cells accumulated in the sinuses and intersinusoidal tissue. These cells expressed the S-100-/CD 11b+/CD 11c+/CD 14+/CD 16+/CD 33+/CD 36+/lysozyme+/MAC 387+/HLA-DR+ phenotype. These recently immigrated monocytes might represent the immediate precursors of SHML cells.

The clinical, radiographic and histological features of a case of eosinophilic gastritis in a 26 year old-man without personal or familial signs of allergy are reported. The Authors pointed out the importance of radiographic and histological aspects of the case studied. Therefore they represent essential methods for a correct diagnosis and an appropriate management that in this case is only pharmacological. The diagnosis of eosinophilic gastritis is, however, important for the recognition of specific allergens.

We describe the case of a young male affected by chronic pustular psoriasis of the lips that remained the only manifestation of acrodermatitis continua of Hallopeau (ACH) for years before the onset of the characteristic hand lesions.

Bone marrow biopsy was performed routinely on 1,068 patients and 1,268 biopsies were obtained. In 547 epithelial tumors bone marrow involvement was present in 95 patients (17.4%); no metastatic involvement was found in 41 cases of nonepithelial tumors. Bone marrow metastases were present mainly in prostatic (54.1%), breast (26.5%), gastric (18.5%) and lung cancer (7.9%). In 26 cases the primary location was initially unknown; histology was useful in the detection of primary tumors. Histology was compared either with aspiration cytology or with bone X-ray and scan.

A patient who had a plaque on his forehead as the first sign of chronic myelomonocytic leukemia (CMML) is described. Histologic studies, which formerly led to the misdiagnosis of non-Hodgkin's lymphoma, revealed CMML with an unusual phenotype. This represents a rare type of CMML for the following reasons: (1) specific cutaneous involvement is rarely the first sign of CMML; (2) the unique phenotype was detected by immunohistology on lesional skin, specifically, the leukemic infiltrate was CD4-positive and notably negative for CD15, the pan myeloid/monocytic marker.