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Notes: Abstract:  The aim of the present study was to identify genetic aberrations in a series of patients with cutaneous large B-cell lymphoma (LBCL) using comparative genomic hybridization (CGH). Eighteen consecutive patients with primary (13 patients) (PCLBCL) and secondary (five patients) (SCLBCL) cutaneous large B-cell lymphoma were included in the study. Nine cases corresponded to PCLBCL leg type and four cases primary cutaneous follicle centre-cell lymphoma (PCFCL). Chromosomal imbalances (CIs) were detected in 14 of 18 samples (77.8%). All of nine cases with PCLBCL leg type and two of four cases with PCFCL showed CIs (100% and 50%, respectively). Regarding SCLBCL, in three of five cases (60%), CIs were detected. The most frequently detected gains involved 2q, 5q, 3 and 7q and amplifications affected 18, 12 and 13. Frequent losses were found in 17p. In PCLBCL leg type, the most frequent gains involved 2q and 7q, amplifications were localized in chromosomes 12, 13 and 18 and losses affected chromosomes 17p and 19. In PCFCL, gains located in 3q, 4 and 7q were found. Our study seems to confirm clear-cut differences between primary cutaneous LBCL and nodal diffuse LBCL, and it suggests the presence of genotypic differences between cases of PCLBCL leg type and cases of PCFCL.

Notes: Background  The clinical mucocutaneous manifestations of glucagonoma syndrome are recognized easily when they occur in the classic pattern of acral or periorificial lesions evolving in recurrent crops, with an annular and migratory distribution, in a patient with diabetes mellitus who has had recent weight loss and anemia. Not infrequently, noncharacteristic clinical and histopathologic features are observed and, in these cases, the diagnosis of pancreatic neoplasm may be delayed.Aim  To review the clinical and histopathologic features of cutaneous manifestations of glucagonoma syndrome.Methods  The clinicopathologic features of 13 patients (eight women) with widespread or localized cutaneous eruption as a manifestation of islet cell pancreatic carcinoma with marked glucagon secretion (glucagonoma) were reviewed.Results  The definitive diagnosis of the cutaneous eruption was established at the time of diagnosis of the pancreatic neoplasm (three patients) or afterwards (10 patients). In nine patients, the mucocutaneous manifestations preceded the diagnosis of the pancreatic neoplasm by 1 month to 3 years (mean, 12 months). In only eight biopsy specimens were the histopathologic features considered to be suggestive or characteristic of necrolytic migratory erythema. Diffuse parakeratosis, that occasionally arose abruptly from normal epidermis, was observed in 12 biopsy specimens. By the time necrolytic migratory erythema was diagnosed, the pancreatic carcinoma had metastasized to the liver, regional lymph nodes, or bone in 12 patients.Conclusion  Increased awareness of the polymorphic mucocutaneous and nonspecific histopathologic features of glucagonoma syndrome is needed to avoid unnecessary delay in the diagnosis of this syndrome.

Notes: A 76-year-old patient was admitted to our hospital with dyspnea. His past medical history disclosed a 17-year duration of polycythemia vera with thrombocytosis; arterial hypertension; diabetes mellitus; hyperuricemia; auricular fibrillation; and chronic bronchitis. He had been treated with hydroxyurea, digoxin, allopurinol, and enalapril. Although pulmonary embolism was not demonstrated, at admission, as a result of the presence of thrombocytosis and arrhythmia, prophylactic treatment with subcutaneous enoxaparin, 60 mg twice daily, was prescribed.Five days after the first injection, two symmetric erythematous patches, 5 cm in diameter, were noted at the abdominal wall area coincident to the points of subcutaneous enoxaparin injection. During the following 24 h, the lesions enlarged and evolved to form purplish-blue necrotic plaques, 15 cm × 5 cm in diameter (〈link href="#f1 #f2"〉Figs 1 and 2). The development of this localized side-effect led to the discontinuation of treatment with enoxaparin.〈figure xml:id="f1"〉1〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD2326:IJD_2326_f1"/〉Symmetric plaques of abdominal skin necrosis〈figure xml:id="f2"〉2〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD2326:IJD_2326_f2"/〉Purplish-blue necrotic plaque, 15 cm × 5 cm in diameterA skin biopsy taken from the margin of the lesion showed multiple fibrin thrombi in the dermal microvasculature with ischemic necrosis of the overlying epidermis (〈link href="#f3"〉Fig. 3). Routine laboratory testing showed: hemoglobin, 74 g/L; white blood cell count, 28.5 × 109/L; platelets, 1025 × 109/L; creatinine, 1.5 mg/dL; and uric acid, 11.8 mg/dL. Coagulation studies showed: prothrombin time ratio, 1.17; thromboplastin time ratio, 1.36; fibrinogen, 3.6 g/L; normal protein C; and negative lupic anticoagulant factor. In contrast, protein S function was reduced: 56% (normal, 71–142%) with low free protein S (63%; normal, 72–139%) and normal total protein S (protein S deficiency type III). Immunoglobulin G (IgG) antiphospholipid antibody was normal, but IgM was increased to 4.25 (normal, 〈 3.1). Heparin–platelet factor 4 (PF4) antibodies were also demonstrated. There was no significant change in the platelet count throughout the patient's admission.〈figure xml:id="f3"〉3〈mediaResource alt="image" href="urn:x-wiley:00119059:IJD2326:IJD_2326_f3"/〉Superficial dermal vascular occlusion and ischemic necrosis of the epidermis (hematoxylin and eosin; original magnification, ×60)The lesions were treated locally, and complete healing was observed after approximately 1 month.Skin necrosis is a rare complication of subcutaneous low-molecular-weight heparin injections. Heparin-induced skin necrosis is now thought to be caused by an antibody-mediated local prothrombotic condition associated with platelet activation and increased thrombin production.The association of heparin-induced skin necrosis with antibodies directed against PF4 is a well-established phenomenon. The concomitant participation of other procoagulant factors, however, has received little attention in the literature.The observation of heparin-induced skin necrosis should motivate a systematic search for the presence of anti-PF4 antibodies, but also for additional genetic or acquired procoagulant factors. As heparin-induced skin necrosis may be a marker for increased risk of systemic arterial or venous thromboembolism, an increased awareness regarding the significance of this potential side-effect is important in order to avoid further potentially severe associated complications.

Notes: A 70-year-old woman was admitted in November 1991 for Internal fixation of a left pertrochanteric fracture. On admission, several indurated plaques and nodules were noted. Two days later she developed an acute and severe episode of rectal bleeding.The patient had a 7-month history of recurrent painful erythematous plaques and nodules on the lower extremities associated with fever and malaise. In September 1991, she was admitted to another institution for evaluation and treatment. At that time, a skin biopsy specimen from a nodular lesion showed a lobular panniculitis. She was diagnosed as having Weber-Christian disease and treatment with prednjsone, 1 mg/kg, was prescribed. In spite of this therapy, new skin nodules appeared.On admission to our institution, physical examination revealed a febrile (38.5 °C) woman, with six to 10 tender erythematous plaques and nodules, 1–3 cm in diameter, distributed over the legs, anterior chest, arms, and abdomen. Some of the nodules were ulcerated in the centers (Fig. 1). A nontender splenomegaly was present, but no enlarged lymph nodes were noted.Laboratory tests showed anemia (hemoglobin 7.9 g/dL), a platelet count of 105×109/L, and a normal leukocyte count and differential. Subsequent laboratory studies showed progressive thrombocytopenia (platelet count, 26×109/L) and leukopenia (leukocyte count, 3.5×109/L), mild hepatic dysfunction (serum glutamate oxalacetic transaminase (SGOT), 68 U/L; serum glutamate pyruvate transaminase (SGPT), 68 U/L; 31 U/L), and lactic dehydrogenase (LDH) (2365 U/L). The rest of the laboratory data, including coagulation studies, urinalysis, screening for connective tissue disorders, pancreatic enzyme levels, VORL, and serologic tests for hepatitis B and C, were normal or negative/nonreactive. Blood cultures, cerebrospinal fluid examination, and chest roentgenogram were also normal. Abdominal computed tomographic (CT) scan revealed only an enlarged spleen.The patient's general condition markedly deteriorated and extensive hemorrhages from venpuncture sites, epistaxis, and rectal bleeding developed. Further treatment with 6-methyl-prednisolone, 160 mg/day, and an i.v. pulse of 1 g cyclophosphamide was initiated, but marked leucopenia ensued. The patient died 23 days after admission. Histopathologic, immunohistochemical, and genotypic studies Skin biopsy specimens from two nodules showed a dense mononuclear, mainly perivascular, infiltrate in the mid- and deep dermis extending into the subcutis (Fig. 2). No epidermotropism was seen. The infiltrate consisted of atypical, small and medium-sized lymphoid cells with irregular nuclei, prominent nucleoli, and frequent mitotic figures. Angioinvasion in the deep skin dermis and subcutaneous septa was noted (Fig. 3). In the subcutaneous tissue, large histiocyte-appearing cells with pale-staining cytoplasm filled with cellular debris (bean-bag cells) were seen admixed within the infiltrate (Fig. 4). The lymphoid cells stained strongly with T-cell markers (UCHL-1, CD3) and the larger histiocytic cells were positive with Mac-387 (++), a-antitrypsin, a-antichymotrypsin (+++), and lysozyme (+). Some of these macrophages also stained weakly positive with T-cell and B-cell markers (L26, CD45RA). Scattered CD30+ cells were also observed within the infiltrate. No frozen material was available for immunohistochemical studies.Immunohistochemical staining with monoclonal antibody anti-Epstein-Barr virus directed against latent membrane protein (LMP-1) (Dako-EVB, CS 1-4) revealed cytoplasmic staining with peripheral reinforcement of scattered atypical lymphoid cells. Studies to defect Epstein-Barr virus DNA were not performed. A postmortem skin biopsy specimen from a nodular lesion showed extensive necrosis of the subcutaneous tissue with some atypical lymphocytes still present in the septa.The bone marrow showed cellular hyperplasia with no evidence of lymphoma. Occasional phagocytic cells with hemophagocyfosis were observed. Genotypic analysis (Southern blot, C-beta probe) from a postmortem skin biopsy failed to demonstrate a clonal T-cell receptor gene rearrangement.

Notes: Three cases of nodular-cystic fat necrosis presenting with focal lipomembranous changes are reported. The lesions consisted of solitary (cases 1 and 3) or multiple (case 2) subcutaneous nodules on the upper (case 1) or lower (cases 2 and 3) extremities which had evolved over weeks to years. At surgical excision, solitary or multiple, freely mobile nodules within a cystic cavity were observed. Histologically, encapsulated fat nodules showing variable amounts of necrosis without marked inflammatory changes were present. Focal lipomembranous changes were observed in some nodules. Our observations seem to support the concept that lipomembranous changes are nonspecific and uncommon patterns of fat necrosis caused by a wide variety of local or systemic events that may cause a compromise in the blood supply of the subcutaneous tissue.

Notes: We report a patient who presented with a papular pruritic eruption of a 3-month duration that histologically showed suprabasal acantholysis accompanied of an eosinophilic inflammatory infiltrate that was consistent with the diagnosis of Grover's disease. Later, erythematous plaques and vesicles appeared which showed a histopathological pattern of eosinophilic spongiosis. The direct immunofluorescence (DIF) study showed lineal IgG and C′3 at the dermal epidermal junction which was consistent with the diagnosis of bullous pemphigoid. No anti-intercellular deposits of immunoglobulin G (IgG) or C′3 were observed. We consider that suprabasal acantholysis may represent the early phase of bullous pemphigoid.

Notes: Background: Expression of CD30 antigen is a distinct marker of lymphocyte activation that was originally described in the Reed–Sternberg cells of Hodgkin's disease. The observation of CD30+ cells has been considered a diagnostic feature of cutaneous CD30 lymphoid proliferations. However, CD30 expression has also been reported in some cutaneous benign inflammatory infiltrates. Methods: Eleven skin biopsies from patients with scabies were double-blindly and retrospectively analysed. A panel of histopathological parameters and immunophenotypic expression of CD4, CD8, CD30 and S-100 antigens was studied. CD30 and S-100 antigens expression were related to clinical features. Results: Large CD30+ cells were demonstrated in eight (8/11) biopsies, corresponding to patients with long-standing lesions (3 months or longer). However, no expression of the CD30 antigen was observed in all biopsy specimens (3/11) corresponding to early lesions (2 months or less). The presence of S-100 positive cells in the papillary dermis was an almost constant feature. Conclusions: CD30+ large cells seem to be a common feature in long-standing infiltrates of scabies. CD30 expression in scattered cells of a cutaneous lymphoid infiltrate cannot be assessed as a strong diagnostic argument of neoplastic cutaneous CD30+ lymphoid proliferation (lymphomatoid papulosis/cutaneous CD30+ lymphoma). Therefore, the possibility that large atypical CD30+ cells may be also present in several benign inflammatory diseases should be always considered.