Human epidermal growth factor receptor 2 fluorescence in situ hybridization and P57KIP2 immunohistochemistry using tissue microarray: Improving histopathological subtyping of hydatidiform mole.

INTRODUCTION: Trophoblastic neoplasia is detected in approximately 25% of complete hydatidiform moles (CMs) and 0.5% of partial hydatidiform moles (PMs). Hydatidiform mole (HM) subtyping is important to properly monitor and predict patient outcomes. Ploidy studies generally involve diploid CMs and triploid PMs. P57KIP2, expressed in the maternal genome, is usually not detected in CM. We determined whether HER2 FISH and p57 immunostaining contributed to the histopathological classification of HMs. METHODS: This retrospective cohort study focused on patients diagnosed with HM by histopathological examination who were followed up at a trophoblastic disease center from 2002 to 2017. Pathological samples of 108 products of conception were reviewed and reclassified according to detailed criteria. Tissue microarray technology (TMA) was used for p57 KIP2 immunostaining and HER2 FISH analysis. RESULTS: Histopathological review showed 57 (53%) CMs, 47 (43%) PMs and 4 (4%) inconclusive cases. P57 immunostaining revealed 59 (55%) negative and 22 (20%) positive specimens, and 27 (25%) were inadequate for analysis. FISH HER2 detected 68 (63%) diploid and 33 (30%) triploid cases; two (2%) had oncogene amplification. The three strategies led to a diagnostic change in 28 samples (26%). The final diagnosis was CM in 75 cases (70%) and PM in 30 (28%); three cases remained inconclusive. DISCUSSION: TMA is a cost-saving method that allows the simultaneous study of large case series. The combination of histopathology, HER2 FISH and p57 tests can be useful for accurately differentiating CM and PM, thus providing additional information on disease prognosis.

Hemophagocytic lymphohistiocytosis, a rare condition in renal transplant - a case report / Linfohistiocitose hemofagocítica, condição rara no transplante renal - relato de caso

Abstract Hemophagocytic lymphohistiocytosis (HLH) is an uncommon and life-threating condition characterized by major immune activation and massive cytokine production by mononuclear inflammatory cells, due to defects in cytotoxic lymphocyte function. It is even more unusual in renal transplant recipients, in which it is often associated with uncontrolled infection. The mortality is high in HLH and differential diagnosis with sepsis is a challenge. The approach and management depend on the underlying trigger and comorbidities. We report a case of a 50-year-old renal transplant female admitted with fever and malaise 3 months post-transplant and presenting anemia, fever, hypertriglyceridemia, high levels of serum ferritin, and positive CMV antigenemia. Urine was positive for decoy cells and BKV-DNA. Graft biopsy showed CMV nephritis. Both blood and urine cultures where positive for E. coli. Hemophagocytosis was confirmed by bone marrow aspiration. Immunosuppression was reduced, and the patient received high-dose intravenous immunoglobulin and dexamethasone, with complete response after 3 weeks. We highlight the importance of early diagnosis and proper management of a rare and serious condition in a renal transplant patient, which can allow a favorable clinical course and improve survival rate.

Resumo A linfohistiocitose hemofagocítica (LHH) é uma condição incomum e potencialmente fatal, caracterizada por importante ativação imunológica e produção maciça de citocinas por células mononucleares inflamatórias, devido a defeitos na função linfocitária citotóxica. É ainda mais incomum em receptores de transplante renal, nos quais está freqüentemente associada a infecções não controladas. A mortalidade da LHH é alta, e o diagnóstico diferencial com sepse é um desafio. A abordagem e o tratamento dependem do gatilho e das comorbidades subjacentes. Relatamos o caso de uma paciente transplantada renal com 50 anos de idade, admitida com febre e mal-estar 3 meses após o transplante, apresentando anemia, febre, hipertrigliceridemia, níveis elevados de ferritina sérica e antigenemia positiva para CMV. A urina mostrou positividade para células decoy e BKV-DNA. A biopsia do enxerto mostrou nefrite por CMV. Ambas as culturas de sangue e urina foram positivas para E. coli. A hemofagocitose foi confirmada pelo aspirado de medula óssea. A imunossupressão foi reduzida e a paciente recebeu altas doses de imunoglobulina intravenosa e dexametasona, com resposta completa após 3 semanas. Destaca-se a importância do diagnóstico precoce e do manejo adequado de uma condição rara e grave em um paciente transplantado renal, o que pode permitir um curso clínico favorável e melhorar a taxa de sobrevida.

Hemophagocytic lymphohistiocytosis, a rare condition in renal transplant - a case report.

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon and life-threating condition characterized by major immune activation and massive cytokine production by mononuclear inflammatory cells, due to defects in cytotoxic lymphocyte function. It is even more unusual in renal transplant recipients, in which it is often associated with uncontrolled infection. The mortality is high in HLH and differential diagnosis with sepsis is a challenge. The approach and management depend on the underlying trigger and comorbidities. We report a case of a 50-year-old renal transplant female admitted with fever and malaise 3 months post-transplant and presenting anemia, fever, hypertriglyceridemia, high levels of serum ferritin, and positive CMV antigenemia. Urine was positive for decoy cells and BKV-DNA. Graft biopsy showed CMV nephritis. Both blood and urine cultures where positive for E. coli. Hemophagocytosis was confirmed by bone marrow aspiration. Immunosuppression was reduced, and the patient received high-dose intravenous immunoglobulin and dexamethasone, with complete response after 3 weeks. We highlight the importance of early diagnosis and proper management of a rare and serious condition in a renal transplant patient, which can allow a favorable clinical course and improve survival rate.

Nanographene oxide-methylene blue as phototherapies platform for breast tumor ablation and metastasis prevention in a syngeneic orthotopic murine model.

BACKGROUND: In the photodynamic therapy (PDT), the photosensitizer absorbs light and transfers the energy of the excited state to the oxygen in the cell environment producing reactive oxygen species (ROS), that in its turn, may cause cell damage. In the photothermal therapy (PTT), light also is responsible for activating the photothermal agent, which converts the absorbed energy in heat. Graphene oxide is a carbon-based material that presents photothermal activity. Its physical properties allow the association with the photosensitizer methylene blue and consequently the production of ROS when submitted to light irradiation. Therefore, the association between nanographene oxide and methylene blue could represent a strategy to enhance therapeutic actions. In this work, we report the nanographene oxide-methylene blue platform (NanoGO-MB) used to promote tumor ablation in combination with photodynamic and photothermal therapies against a syngeneic orthotopic murine breast cancer model. RESULTS: In vitro, NanoGO-MB presented 50% of the reactive oxygen species production compared to the free MB after LED light irradiation, and a temperature increase of ~ 40 °C followed by laser irradiation. On cells, the ROS production by the nanoplatform displayed higher values in tumor than normal cells. In vivo assays demonstrated a synergistic effect obtained by the combined PDT/PTT therapies using NanoGO-MB, which promoted complete tumor ablation in 5/5 animals. Up to 30 days after the last treatment, there was no tumor regrowth compared with only PDT or PTT groups, which displayed tumoral bioluminescence 63-fold higher than the combined treatment group. Histological studies confirmed that the combined therapies were able to prevent tumor regrowth and liver, lung and spleen metastasis. In addition, low systemic toxicity was observed in pathologic examinations of liver, spleen, lungs, and kidneys. CONCLUSIONS: The treatment with combined PDT/PTT therapies using NanoGO-MB induced more toxicity on breast carcinoma cells than on normal cells. In vivo, the combined therapies promoted complete tumor ablation and metastasis prevention while only PDT or PTT were unable to stop tumor development. The results show the potential of NanoGO-MB in combination with the phototherapies in the treatment of the breast cancer and metastasis prevention.

BK polyomavirus nephropathy in two kidney transplant patients with distinct diagnostic strategies for BK virus and similar clinical outcomes: two case reports.

BACKGROUND: BK polyomavirus-associated nephropathy is an important cause of post-transplantation renal failure. We present two cases of BK polyomavirus-associated nephropathy who were submitted to contrasting strategies of clinical follow-up to BK polyomavirus reactivation, but progressed to a similar final outcome. CASE PRESENTATION: Case 1 is a 37-year-old white man whose graft had never presented a good glomerular filtration rate function, with episodes of tacrolimus nephrotoxicity, and no urinary monitoring for BK polyomavirus; stage B BK polyomavirus-associated nephropathy was diagnosed by biopsy at 14 months post-transplant. Despite clinical treatment (dosage decrease and immunosuppressive drug change), he progressed to stage C BK polyomavirus-associated nephropathy and loss of graft function 30 months post-transplant. Case 2 is a 49-year-old mulatto man in his second renal transplantation who was submitted to cytological urinary monitoring for BK polyomavirus; he presented early, persistent, and massive urinary decoy cell shedding and concomitant tacrolimus nephrotoxicity. Even with decreasing immunosuppression, he developed BK polyomavirus-associated nephropathy 1-year post-transplant. Loss of graft function occurred 15 months post-transplant. CONCLUSIONS: Cytological urinary monitoring was an efficient strategy for monitoring BK virus reactivation. Decoy cell shedding may be related to BK polyomavirus-associated nephropathy when extensive and persistent. The presence of associated tacrolimus nephrotoxicity may be a confounding factor for the clinical diagnosis of BK polyomavirus-associated nephropathy.

A Rare Case of Ascites due to Peritoneal Amyloidosis.

BACKGROUND: The clinical manifestations of amyloidosis depend on the type of insoluble protein as well as the location of amyloid deposits in tissues or organs. In the gastrointestinal tract, the small intestine is the most common site of amyloid deposits, whereas peritoneal involvement and ascites are rare. CASE REPORT: We report on a case of ascites due to peritoneal amyloidosis. A 65-year-old patient was admitted to our institution due to anasarca and pulmonary congestion, mimicking heart failure. We started the patient on diuretics and vasodilators. Despite improvement in pulmonary congestion and peripheral edema, his ascites was not reduced. Echocardiogram revealed restrictive cardiomyopathy and a speckle-tracking pattern suggestive of cardiac amyloidosis. Subcutaneous and peritoneal biopsies revealed amyloidosis. CONCLUSIONS: Amyloidosis is rare in the peritoneum and is usually asymptomatic. Ascites occurs in only 20% of patients with peritoneal amyloidosis. We searched PubMed using "ascites" and "amyloidosis" and identified only eight case reports of amyloidosis with ascites. Physicians should be particularly careful in heart failure and anasarca cases when ascites is disproportional or not responsive to diuretic treatment. To date, there is no specific treatment for peritoneal amyloidosis.

Multifocal choroiditis in disseminated Cryptococcus neoformans infection.

PURPOSE: To report an uncommon case of multifocal choroiditis as the result of disseminated Cryptococcus neoformans infection in a patient who is HIV-positive. DESIGN: Interventional case report. METHODS: A 27-year-old HIV-positive woman with fever, headache, and vomiting was examined. Lumbar puncture was performed and revealed C neoformans infection. Her condition evolved with sudden bilateral blindness and deafness. Ophthalmologic examination revealed multiple yellowish choroidal lesions in the posterior pole of both eyes. RESULTS: Postmortem examination showed disseminated C neoformans infection. Histologic examination of the eyes confirmed the presence of C neoformans in the choroiditis. CONCLUSION: Multifocal choroiditis in C neoformans infection is a rare ophthalmic manifestation. The recognition of this condition by ophthalmologists can help physicians to diagnose a disseminated and fatal disease.

Condyloma acuminatum: its histopathological pattern

Condyloma acuminatum is one of the clinical manifestations of papillomavirus infection. The classical histopathological features are already known and do not constitute a diagnostic problem. Clinically it has been classified into growth or proliferative, full-expression, and regressive or persistent phases, with the histopathological aspects of these distinct phases being well documented in equine cutaneous papillomas. We have designed a protocol of histopathological analysis in order to investigate the possibility of indentifying the evolutional phases in human condylomata acuminata. Sixty condylomata acuminata from the files of the Department of Pathology, Universidade Federal Fluminense, were studied regarding koilocytosis, paraceratosis, acantosis, basal cell hyperplasia and mononuclear cell infiltrate. After an individual analysis and comparison of the cases, the main differential aspects of condyloma acuminatum were: koilocytosis, transepithelial lymphocytic infiltrate and basal cell hyperplasia. Thus, condylomatous lesions can be histopathologically differentiated in three major patterns: proliferative, viral replication activity and regressive.