Mutational status of naevus-associated melanomas.

BACKGROUND: The origin of melanoma has always been a debated subject, as well as the role of adjacent melanocytic naevi. Epidemiological and histopathological studies point to melanomas arising either de novo or from a naevus. OBJECTIVES: To evaluate the presence of mutations in genes from well-known melanomagenesis pathways in a large series of naevus-associated melanomas. MATERIALS AND METHODS: Sixty-one melanomas found in association with a pre-existing naevus were microdissected, after careful selection of cell subpopulations, and submitted to Sanger sequencing of the BRAF, NRAS, c-KIT, PPP6C, STK19 and RAC1 genes. Each gene was evaluated twice in all samples by sequencing or by sequencing and another confirmation method, allele-specific fluorescent polymerase chain reaction (PCR) and capillary electrophoresis detection or by SNaPshot analysis. Only mutations confirmed via two different molecular methods or twice by sequencing were considered positive. RESULTS: The majority of cases presented concordance of mutational status between melanoma and the associated naevus for all six genes (40 of 60; 66.7%). Nine cases presented concomitant BRAF and NRAS mutations, including one case in which both the melanoma and the adjacent naevus harboured V600E and Q61K double mutations. In two cases, both melanoma and associated naevus located on acral sites were BRAF mutated, including an acral lentiginous melanoma. CONCLUSIONS: To our knowledge this is the largest naevus-associated melanoma series evaluated molecularly. The majority of melanomas and adjacent naevi in our sample share the same mutational profile, corroborating the theory that the adjacent naevus and melanoma are clonally related and that the melanoma originated within a naevus.

Cutaneous immediate and late phase reactions to schistosomin in schistosomiasis patients.

Cutaneous immediate and late phase reactions (LPR) to schistosomin were studied in 29 patients with schistosomiasis mansoni. In 12 of these patients, the determination of total and specific serum IgE by immunoenzymatic method against schistosome antigen was carried out using serum samples obtained on the same day as the cutaneous tests. Skin biopsies were taken from 4 typical LPRs. Immediate reactions occurred in all except one and LPRs in 12 (41.3%). Patients with positive cutaneous reactions had highe levels of specific serum IgE against schistosome antigen. Histopathological studies showed a moderate exudate consisting mainly of neutrophils (60%) and eosinophils (40%). LPRs in schistosomiasis have the same characteristics reported in the medical literature in relation to time of appearance, morphology and histopathology. The immunopathogenic role played by LPRs in the patients remains to be clarified.

Comparison of the cell walls of Paracoccidioides loboi and Paracoccidioides brasiliensis by using polysaccharide-binding dyes.

Biopsies from patients with Jorge Lobo's disease (keloid blastomycosis) and paracoccidioidomycosis (South American blastomycosis), caused respectively by Paracoccidioides loboi a non-cultivated fungus and Paracoccidioides brasiliensis, were stained with six different dyes having the property of forming complexes with some polysaccharides and oligosaccharides. The cell-walls of both fungi showed similar staining characteristics, suggesting a similar chemical structure. The role of the fungal cell-walls in evasion mechanisms is discussed.

A new morphological concept and classification of granulomatous inflammation: the polar granulomas.

An historical analysis of granulomas and a new morphological concept and classification of granulomatous inflammation, the polar-granulomas, are presented. The historical analysis of the concept of granulomas reveals that the still proclaimed confusion concerning the process was due more to Virchow's comparison of granulomas to ordinary granulation tissue than to tumors and to objections of pathologists to Metchnikoff's theory of phagocytosis. And it is strange to verify that differences between granulomas and granulation tissue, although already established in the end of the 19th Century, were overlooked by the majority of pathologists. In this Century , the knowledge of granulomatous inflammation was greatly improved by Aschoff 's concept of reticulum endothelial system, Mitsuda test for types of leprosy, Jadassohn- Lewandowsky law, South American classification of leprosy into polar forms, and Forbus contribution to histogenesis and morphological classification of granulomas. The best model for the study of granulomatous inflammation is leprosy, because this disease is characterized by two different clinical polar forms, each one having particular types of phagocytosis (complete or incomplete) and of granulomas (tuberculoid or non tuberculoid). Based on the phenomenon of phagocytosis, polar forms of leprosy, Jadassohn- Lewandowsky law, metamorphosis of macrophages and nature of the etiologic agent, granulomas can be defined as a reactional hyperplasia of macrophages towards inanimate agents and towards animate agents of low virulence. Also based in the same data, a morphological classification of granulomas into polar types, tuberculoid and non tuberculoid, is proposed. The polar tuberculoid type follows the Jadassohn- Lewandowsky law, its etiologic agent is absent or scarce (complete phagocytosis) - and comprise two sub-types: tubercle-like and sarcoid-like. The polar non tuberculoid type does not follow the Jadassohn- Lewandowsky law, its etiologic agent is always present or copious (incomplete phagocytosis) and comprises two sub-types: giant cell and persistent macrophage. In the latter case, macrophages behave as a culture medium cell or as a storage cell. When both polar tuberculoid and non tuberculoid structures are found together in the same disease, granuloma can be called interpolar . If both types occur simultaneously in the same disease, granuloma would be bipolar. It seems that the proposed definition of granulomas combines morphology with functional activity of macrophages, easily observed in routine histopathological examination by optical microscopy. This morphological classification into polar granulomas (ABSTRACT TRUNCATED AT 250 WORDS)

[Importance of Perls stain in histologic diagnosis of Kaposi sarcoma]. / Intérêt de la coloration de Perls dans le diagnostic histologique du sarcome de Kaposi.

The authors studied 27 cases of Kaposi's sarcoma, 23 cases of pyogenic granuloma, 18 cases of hemangioma, 17 cases of stasis dermatitis and 9 cases of dermatofibroma. In all these cases, they used the hematoxylin-eosin stain and Perls' stain', and they showed the presence of hemosiderin in all the cases of Kaposi's sarcoma and stasis dermatitis. The hemangioma and the dermatofibroma presented 50% of positivity, and the pyogenic granuloma, only 26.1%.

Acquired immune deficiency syndrome (AIDS) in Brazil. Necropsy findings.

According to the 15 autopsies performed at the Department of Pathological Anatomy, Escola Paulista de Medicina, São Paulo, Brazil, it was confirmed that acquired immunodeficiency syndrome (AIDS) occurs preferably in young homosexual males, who die in a short period of time of the disease, which leads to a consumptive state verified by cachexia of the cadavers. The most affected organs of this series were the lungs and encephalum, exactly the ones responsible for the immediate cause of death. In this series of autopsies there were 9 types of microorganisms represented by virus, bacteria, fungi, protozoans and two types of tumors, Kaposi's sarcoma and lymphoma of the central nervous system. From the microorganisms, the most frequent was the Cytomegalovirus and, from the tumors, Kaposi's sarcoma. The various types of microorganisms were frequently associated, principally in the central nervous and digestive systems. There was also association of microorganisms with tumors. Besides the lesions produced by microorganisms there were other associated alterations as brown atrophy of neuronia, which was related to the infiltration of cerebral lymphoma, and the lymphocytic depletion of lymphoid organs due to immunological exhaustion. Cellular reaction to microorganisms was practically none, principally with Pneumocystis carinii and Cryptococcus neoformans, the first one behaving as an inert mould in the pulmonary alveoli and the second proliferating freely in tissues. In two cases there was no granulomatous reaction to Mycobacterium tuberculosis. The primary lymphoma of the central nervous system should be interpreted as a microglioma, i.e., a reticulosarcoma of this system according to Hortega's school.

PIP: Clinical and autopsy findings obtained from 15 male patients treated for acquired immunodeficiency syndrome (AIDS) at 3 hospitals in Sao Paulo provided a clearer profile of AIDS cases in Brazil. Of the 12 patients whose sexual orientation was recorded, 9 were homosexual and 3 were bisexual. 75% were between the ages of 22-36 years; 14 were white. The duration of diseases ranged from 14 days-7 months in this series, confirming the rapid evolution of AIDS from 1st symptom to death. The most common clinical manifestations of disease were fever, cough, weight loss, diarrhea, and lymphadenopathy. Organs most frequently involved were the lungs (13 cases) and encephalum (9 cases). Microscopic findings revealed 9 types of microorganisms, fungi, and protozoa, the most common of which was Cytomegalovirus (7 cases). The cause of death was meningoencephalitis in 7 cases and panlobar pneumonia in 3 cases. The incidence of Kaposi's sarcoma (2 cases) was surprisingly low in this series. In addition to lesions produced by microorganisms, there were important associated lesions represented by lymphocytic depletion, acute myocarditis, brown atrophy of neuronia, acute pancreatitis, and liver cirrhosis. Several microorganisms and tumors in these AIDS patients were discovered only at autopsy, confirming the importance of necropsy to the study of the natural history of this disease. An unexpected pathological finding in this series was the absence of cellular reactions to microorganisms, particularly Pneumocystis carinii, Cryptococcus neoformans, and Mycobacterium tuberculosis.

Langerhans cell histiocytosis.

The authors present a rare case of Langerhans cell histiocytosis in a 31 year old female patient with vulvar, peri-anal and oral lesions, diabetes insipidus, pulmonary skin and bone infiltrations. Skin biopsy immunohistochemistry presented positive S100 protein and vimentin, but the diagnosis was done with the demonstration of Birbeck granules with electronic microscopy. The treatment was based on systematical chemotherapy although vulvar lesion has a bad response to chemotherapy.

Hereditary hemorrhagic telangiectasia associated to chronic active hepatitis.

Hereditary hemorrhagic telangiectasia or Rendu-Osler-Weber syndrome (ROWS) is an angiodisplasia characterized clinically by the presence of telangiectasias in the skin and mucosas, particularly on the face, conjunctivas, nose, pharynx and rarely on the thorax. Visceral involvement specially hepatic cirrhosis associated with pulmonary arteriovenous fistulae have been described. We describe a 7 10/12 years old girl with the diagnosis of ROWS associated with chronic active hepatitis with positive HBAg that evolved to hepatic cirrhosis. This is the second case of ROWS associated with chronic active hepatitis reported in the literature, being however, the first one described in the childhood.

[Reactive perforating collagenosis associated with chronic renal insufficiency and diabetes mellitus]. / Colagenose reativa perfurante associada à insuficiência renal crônica e diabetes mellitus.

Reactive perforating collagenosis is an uncommon skin disorder characterized by extrusion of collagen fibers through the epidermis. The lesions may appear in infancy, from genetic inheritance, or in adulthood in association with diabetes mellitus and/or chronic renal insufficiency. One case of reactive perforating collagenosis is reported, in a 42 year old man, with chronic renal failure diabetes mellitus and undergoing hemodialysis. The literature was reviewed on perforating dermatoses in adults associated with diabetes and chronic renal insufficiency.

[Idiopathic skin calcinosis with transepithelial elimination]. / Calcinose cutánea idiopática com eliminação transepitelial.

A case of universal cutaneous calcinosis developed without apparent cause is reported. It had an evolution towards epidermic perforation and was treated with aluminium hydroxide. A discussion was made on the rarity of the idiopathic calcinosis as well as on the interesting phenomenon of transepidermal elimination.

[Association of Virchowian hanseniasis, dermatopolymyositis and gastric adenocarcinoma. Report of a case]. / Associação entre hanseníase virchowiana dermatopolimiosite e adenocarcinoma gástrico--relato de um caso.

The authors report a case of lepromatous leprosy associated with dermatopolymyositis and gastric adenocarcinoma. The literature is reviewed and the authors discuss about this association.

[Annular granuloma in HIV-positive patient]. / Granuloma anular en paciente HIV-positivo.

The Authors present a HIV-positive patient with atypical lesions of Granuloma annulare near the joints. Ten HIV-positive patients with Granuloma annulare have been reported until now in the world literature, and these cases are reviewed.

Comparative study of direct and indirect immunofluorescence for diagnosis of canine pemphigus foliaceus / Estudo comparativo da imunofluorescência direta e indireta para o diagnóstico do pênfigo foliáceo canino

Pemphigus foliaceus (PF) is the most common autoimmune skin disease in dogs. It is characterized by pustules, erosions, and crusts which occur due to the presence of autoantibodies that target intercellular adhesion. Histopathological examination is considered the gold standard pattern in the diagnosis, but may sometimes be inconclusive, especially when the characteristic findings are not identified. New diagnostic tests are continuously being developed and immunofluorescence assays, could be a valuable alternative diagnostic tool. This study aimed to evaluate the applicability of direct and indirect immunofluorescence (DIF and IIF) tests for the diagnosis of canine PF. Twenty eight dogs were divided into two groups: Group I with 14 dogs with PF and Group II (control) with 14 dogs with Superficial pyoderma (differential diagnoses of PF). All animals were submitted to skin biopsy to histopathological and DIF. Blood samples were collected to assess IIF. Comparing the DIF results against the histopathology test, there was an agreement of 75% (9/12) with a Kappa index of 0.77 (P<0.001). Considering IIF, the agreement was 100% (14/14), with a Kappa index of 1.0 (P<0.001). We conclude that DIF and IIF are highly effective and were useful and effective complementary examination tests for an improvement in the diagnosis of canine PF.(AU)

O pênfigo foliáceo (PF) é considerado uma das doenças tegumentares autoimunes mais frequentes em cães. Clinicamente, caracteriza-se pela presença de pústulas, erosões e crostas. O exame histopatológico é considerado o teste diagnóstico de eleição, porém pode se mostrar inconclusivo, sobretudo quando os achados característicos da doença não são observados. Novas ferramentas diagnósticas têm sido desenvolvidas e os testes de imunofluorecência são uma valiosa alternativa. Este estudo teve como objetivo avaliar a aplicabilidade das reações de imunofluorescência direta (IFD) e indireta (IFI) para o diagnóstico do PF canino. Vinte e oito cães foram divididos em dois grupos: grupo I com 14 cães com PF e grupo II (controle) com 14 cães com piodermite superficial (um dos principais diagnósticos diferenciais do PF). Todos os animais foram submetidos à biópsia cutânea, seguida de exame histopatológico e IFD. Amostras de sangue foram coletadas para realização da IFI. Comparando-se os valores de IFD com o histopatológico, obtiveram-se valores de concordância de 75% (9/12), com índice Kappa de 0,77 (P<0,001). Já na IFI, a concordância foi de 100% (14/14), com índice Kappa de 1,0 (P<0,001). Concluiu-se, então, que a IFD e a IFI apresentaram excelentes resultados e podem ser consideradas novas alternativas diagnósticas do PF canino.(AU)

Acute Generalized Exanthematous Pustulosis Induced by Cefepime: A Case Report.

Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous rash characterized by widespread sterile nonfollicular pustules. Cefepime is a fourth generation cephalosporin, used to treat severe infections. A 67-year-old man was admitted with acute gastroenterocolitis. On the seventh day, the patient developed a nosocomial pneumonia and cefepime was initiated. On the fourth day of cephalosporin treatment, he presented with a maculopapular, pruritic eruption affecting the face, neck, abdomen and limbs. One day later he developed disseminated pustular lesions and his temperature was 37°C. Laboratory analysis evidenced leukocytosis and skin biopsy showed subcorneal pustule, edema in the papillary dermis, perivascular inflammatory infiltrate consisting of neutrophils, leukocytoclasia and red cell extravasation in the epidermis. Cefepime was suspended and within 4 days the non-follicular pustules cleared following a desquamation. AGEP is a disease attributed to a variety of causes, but in 90% of the cases it is due to an adverse drug reaction. Antibiotics are implicated in 80% of these cases, mostly penicillins and macrolides. There are few cases associated with cephalosporins. It is very important to consider AGEP in cases of acute pustular rashes and drugs should be investigated as causative agents.