RESUMO
Neurofibromatosis type 1 (NF1) is a tumor syndrome and one of the most common genetic disorders. Patients have an increased risk of developing neurologic and gastrointestinal (GI) neoplasms, but GI lesions are often underrecognized since most cases are asymptomatic. It is extremely rare to see multiple types of abdominal tumors synchronously in NF1. In this case, we describe a patient presenting with a small, low-grade periampullary neuroendocrine tumor (NET) that underwent endoscopic submucosal dissection and later pancreaticoduodenectomy (Whipple procedure). This led to findings of lymph node and distant metastasis of her NET, and the incidental discovery of gastrointestinal stromal tumors, extensive pancreatic intraepithelial neoplasia, and main duct and side branch intraductal pancreatic mucinous neoplasm. The synchronous presence of these lesions has not been reported in the literature.
Assuntos
Deficiência de Glucosefosfato Desidrogenase , Supressores da Gota/efeitos adversos , Urato Oxidase/efeitos adversos , Deficiência de Glucosefosfato Desidrogenase/induzido quimicamente , Deficiência de Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/patologia , Supressores da Gota/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Urato Oxidase/administração & dosagemRESUMO
AL amyloidosis is due to deposition of protein derived from immunoglobulin light chain fragments. It is a systemic disorder in which deposition of plasma proteins can adversely affect function of the heart, liver, kidneys, and peripheral nerves. Deposition in the heart results in a decrease in the amplitude of the electrical activity of the heart and can be an early clue to the diagnosis. A 63-year-old male admitted for volume overload was found to have nephrotic range proteinuria, progressive renal insufficiency (Creatinine 4.0 increased from his baseline 0.9), and hypoalbuminemia. On exam, he had diffuse anasarca and peripheral neuropathy. A renal biopsy showed AL amyloidosis, lambda related, involving the glomeruli, interstitium, and arterial walls. Bone marrow biopsy showed 30% plasma cells with lambda light chain predominance. Serum free light chains were elevated. Lamda was 11.50 mg/dL and kappa was 5.12 mg/dL. In retrospective review of his chart, an EKG with low voltage and anterior pseudo-infarct pattern was first apparent on an admission for stroke two years prior. Echocardiogram showed mild concentric left ventricular hypertrophy. The patient was started on chemotherapy with Bortezomib. The differential of a low-voltage EKG includes many common pulmonary and chest wall (COPD, obesity) as well as pericardial diseases (effusions), but also important rarer infiltrative diseases including sarcoidosis and amyloidosis. Amyloidosis of the heart can cause progressive irreversible heart failure, but its progress can be altered if identified early. Physicians should consider amyloidosis when faced with a low-voltage EKG along with systemic symptoms including nephrotic range proteinuria, peripheral neuropathy, hepatosplenomegaly, and macroglossia.
RESUMO
A unique case of a mixed epithelial stromal tumor (MEST) that was predominantly composed of adipose tissue is reported here. Radiographically and grossly, the lesion was thought to be an angiomyolipoma, based upon its fatty appearance. Microscopically, the lesion was predominantly composed of mature adipose tissue but also contained clusters of bland tubules surrounded by smooth muscle bundles and collagen. By immunohistochemistry, the stroma labeled diffusely for estrogen and progesterone receptors, while the muscle bundles labeled for desmin. Melanocytic markers HMB45 and Melan A, typically positive in angiomyolipoma, were nonreactive. This case expands the morphologic spectrum of MEST to include mimics of angiomyolipoma.
Assuntos
Tecido Adiposo/patologia , Angiomiolipoma/patologia , Neoplasias Renais/patologia , Neoplasias Complexas Mistas/patologia , Idoso , Antígenos de Neoplasias/metabolismo , Desmina/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/metabolismo , Neoplasias Renais/cirurgia , Antígeno MART-1 , Antígenos Específicos de Melanoma , Proteínas de Neoplasias/metabolismo , Neoplasias Complexas Mistas/metabolismo , Neoplasias Complexas Mistas/cirurgia , Nefrectomia , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismoRESUMO
Primary thyroid lymphoma, although a rare malignancy, can arise in common chronic inflammatory conditions such as Hashimoto's thyroiditis. Incidental finding of a thyroid nodule with chronic thyroid inflammation warrants further investigation. Early detection of malignancy can play a vital role in improved outcomes. We report a case of a 60-year-old male who presented to the clinic for a routine visit. An enlarged, firm, non-tender thyroid gland was appreciated on exam with high thyroid stimulating hormone (TSH) level. Fine needle aspiration of the mass revealed nonspecific atypical lymphocytes. The pathology and immunohistochemical stains were consistent with histologic impression of extra nodal marginal B-cell lymphoma (mucosa-associated lymphoid tissue [MALT] lymphoma) and Hashimoto's thyroiditis. Patient was treated with thyroxine after complete surgical excision of left thyroid lobe and remains in remission with close follow-up with his primary care provider. Primary thyroid MALT lymphoma follows an indolent process and remains asymptomatic in most patients. These are usually found to arise at sites of ongoing chronic inflammation with underlying autoimmune or infectious etiologies. Treatment modalities include surgical excision and/or radiation therapy for localized lesions, with both radiation and chemotherapy indicated for disseminated disease.
RESUMO
Testicular germ cell tumors (GCT) are the commonest solid tumors in young men. Typical presentation is with painless scrotal swelling; however, symptoms related to complications or metastasis may be the initial presentation. Gastrointestinal (GI) metastasis is seen in about 5% of patients with germ cell tumors and presentation is commonly with GI bleed. It is important to have GCT as a differential diagnosis of GI bleed in young men presenting with unexplained anemia as direct questioning about scrotal swelling and genital examination when appropriate will guide further investigation and facilitate prompt diagnosis. We present a case of a 26-year-old man with testicular germ cell tumor and severe anemia secondary to extension and perforation of duodenum by retroperitoneal metastasis and a review of the literature on the gastrointestinal manifestations of testicular germ cell tumors.
RESUMO
Deletions of portions of chromosomes 1p and 19q are closely associated with the oligodendroglioma histologic phenotype. In most cases, 1p and 19q are codeleted, yet the mechanism of dual loss is unexplained. We report 5 cases (World Health Organization grade III) in which metaphase cytogenetics identified a derivative chromosome consisting of what appears to be the whole arms of 1q and 19p forming a der(1;19)(q10;p10). Metaphase fluorescent in situ hybridization (FISH) confirmed the derivative chromosome was composed of 1q and 19p material in 3 cases; in 2 cases with few metaphases, FISH confirmed 19p material on the derivative chromosome. In all cases, interphase FISH showed net loss of 1p and 19q in 77% to 92% of cells, and microsatellite studies were consistent with 1p and 19q loss. We hypothesize the following: occurrence of a balanced whole-arm translocation between chromosomes 1 and 19 forming 2 derivative chromosomes, one composed of 1q and 19p, the other of 1p and 19q. Subsequent loss of the der(1;19)(p10;q10) then results in the simultaneous 1p and 19q loss observed in oligodendroglioma with retention of the der(1;19)(q10;p10) seen in these cases.
Assuntos
Neoplasias Encefálicas/genética , Cromossomos Humanos Par 19 , Cromossomos Humanos Par 1 , Oligodendroglioma/genética , Translocação Genética , Adulto , Aberrações Cromossômicas , Deleção Cromossômica , Feminino , Humanos , Hibridização in Situ Fluorescente , Perda de Heterozigosidade , MasculinoRESUMO
We present the case of a 6-year-old male who received an allogeneic bone marrow transplant as part of treatment for acute lymphoblastic leukemia. The patient relapsed 5 months after transplantation and received additional chemotherapy. He acquired an angioinvasive fungal infection that required transfusion of granulocytes. Approximately 5 weeks after relapsing (181 days after transplant), a bone marrow specimen was taken for molecular engraftment analysis and flow cytometry to assess graft loss as well as residual disease. The engraftment results generated by the multiple short tandem repeat loci tested were inconsistent, and alleles were present at several loci that were of neither patient nor donor origin. An error in specimen identification was initially considered. Further investigation into the circumstances surrounding procurement of the patient's bone marrow aspirate revealed that the patient had received a granulocyte transfusion approximately 10 hours before the bone marrow specimen was taken. In addition, morphological and flow cytometric analyses of the same bone marrow aspirate demonstrated a significant degree of peripheral blood contamination. We determined that the unknown alleles in the bone marrow engraftment specimen were derived from the donor of the transfused granulocytes. This case illustrates that white cell transfusion can lead to erroneous bone marrow engraftment results, particularly if only one microsatellite locus is used to monitor engraftment.
Assuntos
Transplante de Medula Óssea , DNA/análise , Sobrevivência de Enxerto/genética , Transfusão de Leucócitos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Criança , DNA/genética , Citometria de Fluxo , Granulócitos/transplante , Humanos , Masculino , Repetições de Microssatélites , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Transplante HomólogoRESUMO
Gastric cancer is the 12th leading cause of cancer-related deaths in the United States and commonly metastasizes to the bones. However, the presentation of gastric cancer as bony metastases without preceding gastrointestinal symptoms is rare which has been infrequently reported in the literature. Moreover, leptomeningeal carcinomatosis is an unusual complication of gastric cancer accounting for less than 1 percent of these patients. We present a unique case of a middle aged male who presented to the emergency department with worsening backache which started one month priorly. The only abnormal laboratory test was an elevated alkaline phosphatase of 154 IU/L. The imaging of his spine showed osteolytic lesions which on biopsy revealed signet ring cells. A small 2 cm ulcerated mass was found on esophagogastroduodenoscopy at the gastric cardia which on biopsy revealed signet ring gastric carcinoma. The patient received chemotherapy with capecitabine and oxaliplatin as well as radiation and showed a good response initially. A few months later, he presented with persistent worsening headaches and on brain imaging was found to have leptomeningeal carcinomatosis. Ten months after the diagnosis of gastric carcinoma, he passed away.
RESUMO
Typical papillary hyperplasia, a recently recognized precursor lesion to low-grade papillary urothelial neoplasms, consists of undulating folds of cytologically benign urothelium. Well-developed, branching fibrovascular cores of a papillary neoplasm are not evident. We have noted lesions with the architectural pattern of papillary hyperplasia; however, the overlying urothelium demonstrated varying degrees of cytologic atypia. We identified 15 cases of atypical papillary hyperplasia (13 males, 2 females, age 55 to 92) with overlying urothelium showing cytologic atypia. Of these cases, 8 (53%) were received in consultation. Of the 15 cases, 8 exhibited overlying flat carcinoma in situ (CIS), 4 had overlying dysplasia, and 3 were transitional between papillary hyperplasia with atypia and the earliest lesions of papillary neoplasia. Of these cases, 5 patients had multiple specimens with atypical papillary hyperplasia (range, 2 to 8) over time. Concurrent to the diagnosis of atypical papillary hyperplasia, there were 25 different urothelial lesions: CIS (n = 11), papilloma (n = 1), papillary neoplasm of low malignant potential with CIS (n = 1), high-grade papillary urothelial carcinoma (n = 10; 3 with CIS), small-cell carcinoma (n = 1), and infiltrating urothelial carcinoma (n = 1). Of 11 patients with known prior history, 2 had 12 prior urothelial neoplasms (9 low-grade papillary neoplasms, 2 papillary urothelial neoplasms of low malignant potential, and 1 high-grade papillary cancer). Of 10 patients with atypical papillary hyperplasia and a minimum of 1 year of follow-up, 9 had 19 recurrences: CIS (n = 4), papilloma (n = 1), papillary neoplasm of low malignant potential (n = 1), infiltrating urothelial carcinoma (n = 3; 1 with CIS), and high-grade papillary urothelial carcinoma (n = 10; 5 with invasion and 2 with CIS). Whether the papillary hyperplasia had overlying CIS or dysplasia did not affect the correlation with urothelial neoplasms. Immunohistochemical analysis of p53 and Ki-67 expression in 8 cases demonstrated overexpression of p53 (n = 2; 1 with overlying dysplasia and 1 with overlying CIS), and Ki-67 (n = 5; 2 with overlying dysplasia and 3 with overlying CIS). Taken together, these results suggest that atypical papillary hyperplasia is most frequently associated with CIS and high-grade papillary cancer. In some cases, CIS or dysplasia may evolve into atypical papillary hyperplasia, with further progression to high-grade papillary cancer. This process may be analogous to papillary hyperplasia without cytologic atypia progressing to low-grade papillary urothelial neoplasms.
Assuntos
Carcinoma in Situ/patologia , Lesões Pré-Cancerosas/patologia , Neoplasias da Bexiga Urinária/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma Papilar/patologia , Contagem de Células , Feminino , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade , Papiloma/patologia , Lesões Pré-Cancerosas/metabolismo , Prognóstico , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Urotélio/metabolismo , Urotélio/patologiaRESUMO
Using global gene expression analyses, multiple novel tumor markers overexpressed in infiltrating ductal adenocarcinomas of the pancreas have recently been identified. However, the expression of these markers in morphologically similar adenocarcinomas of the biliary tree has not been investigated. The purpose of the present study was 3-fold. First, we used 8 markers that have been shown to be overexpressed in whole tissue sections of pancreatic adenocarcinomas to validate tissue microarrays (TMAs) created from a series of pancreatic adenocarcinomas (n=68). The labeling patterns of 6 epithelial markers (fascin, mucin 4, 14-3-3sigma, prostate stem cell antigen, topoisomerase IIalpha, and cdc2/p34) were concordant with previously published studies on whole tissue sections, yet required far fewer slides and reagents. Mesothelin, an epithelial marker, and heat shock protein 47, a marker of peritumoral desmoplasia, showed lower levels of expression in the TMAs when compared with whole tissue sections. Second, we examined the previously unknown expression of the same 8 novel tumor proteins in cancers of the biliary tree by using TMAs created from a series of intrahepatic cholangiocarcinomas, gallbladder adenocarcinomas, and adenocarcinomas of the distal common bile duct (n=38). Each of the 8 markers was overexpressed in the biliary cancers, ranging from 14% demonstrating at least focal labeling with prostate stem cell antigen to 100% labeling with cdc2/p34. Most of the markers showed lower frequencies of expression in the biliary tract carcinomas in comparison to the pancreatic adenocarcinomas. In addition, expression patterns varied with location in the biliary system (intrahepatic versus gallbladder versus distal common bile duct). These differences were statistically significant (P<0.05) for mesothelin, mucin 4, and heat shock protein 47. Finally, the expression of selected markers in neoplastic progression of gallbladder cancer was examined. Two markers, fascin and mesothelin, showed up-regulation of expression with transition from carcinoma in situ to invasive adenocarcinoma, implicating a role for these markers in neoplastic progression. The results of this study indicate that TMA technology provides valid and cost-effective means to screen large numbers of novel tumor markers, even in tumors such as pancreatic and biliary adenocarcinomas that characteristically have abundant desmoplastic stroma. In addition, novel tumor markers of pancreatic adenocarcinomas show similar, yet not identical, expression patterns in biliary carcinomas. Therefore, these markers are potentially useful in developing diagnostic tests and treatment paradigms for tumors involving the biliary system.
Assuntos
Adenocarcinoma/metabolismo , Neoplasias do Sistema Biliar/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias Pancreáticas/metabolismo , Análise Serial de Proteínas , Adenocarcinoma/patologia , Ductos Biliares Intra-Hepáticos/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias do Sistema Biliar/patologia , Técnica Indireta de Fluorescência para Anticorpo , Técnicas de Preparação Histocitológica , Humanos , Neoplasias Pancreáticas/patologia , Inclusão em ParafinaRESUMO
OBJECTIVE: To examine the imprint of liquid-based technologies for cervicovaginal cytology on HIV-positive women, who are at high risk for cervical intraepithelial neoplasia. STUDY DESIGN: We performed a retrospective search of the cytopathology files of Johns Hopkins Hospital for the cervicovaginal cytology of HIV-positive women to examine the effect of liquid-based technology on this population. RESULTS: Significant intraepithelial lesions (SILs) (low grade SIL or greater) were identified in 24% of the conventional smears and 23% of the liquid-based cytology. Atypical squamous cells of undetermined significance (ASCUS)/atypical glandular cells of undetermined significance was diagnosed in 15% of the conventional smears and 9% of the liquid-based preparations (P = .02). In patients with ASCUS diagnoses and tissue follow-up within 7 months, significant SILs were identified in 29% with conventional smears and in 65% with liquid-based cytology. CONCLUSION: There was no statistically significant difference in the rate of SILs between conventional smears and liquid-based cervicovaginal preparations in HIV-positive women. The diagnosis of ASCUS on liquid-based cytology may have an increased likelihood of representing a significant SIL in comparison to conventional smears. For the high-risk, HIV-positive population, immediate colposcopy and biopsy may be warranted following ASCUS diagnoses on liquid-based cytology.
Assuntos
Infecções por HIV/complicações , Lesões Pré-Cancerosas/patologia , Displasia do Colo do Útero/patologia , Neoplasias do Colo do Útero/patologia , Esfregaço Vaginal/normas , Adulto , Colo do Útero/patologia , Erros de Diagnóstico/prevenção & controle , Células Epiteliais/patologia , Feminino , Humanos , Seleção de Pacientes , Lesões Pré-Cancerosas/etiologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Neoplasias do Colo do Útero/etiologia , Displasia do Colo do Útero/etiologiaRESUMO
CONTEXT: Pathologists grade follicular lymphoma (FL) cases by selecting 10, random high power fields (HPFs), counting the number of centroblasts (CBs) in these HPFs under the microscope and then calculating the average CB count for the whole slide. Previous studies have demonstrated that there is high inter-reader variability among pathologists using this methodology in grading. AIMS: The objective of this study was to explore if newly available digital reading technologies can reduce inter-reader variability. SETTINGS AND DESIGN: IN THIS STUDY, WE CONSIDERED THREE DIFFERENT READING CONDITIONS (RCS) IN GRADING FL: (1) Conventional (glass-slide based) to establish the baseline, (2) digital whole slide viewing, (3) digital whole slide viewing with selected HPFs. Six board-certified pathologists from five different institutions read 17 FL slides in these three different RCs. RESULTS: Although there was relative poor consensus in conventional reading, with lack of consensus in 41.2% of cases, which was similar to previously reported studies; we found that digital reading with pre-selected fields improved the inter-reader agreement, with only 5.9% lacking consensus among pathologists. CONCLUSIONS: Digital whole slide RC resulted in the worst concordance among pathologists while digital whole slide reading selected HPFs improved the concordance. Further studies are underway to determine if this performance can be sustained with a larger dataset and our automated HPF and CB detection algorithms can be employed to further improve the concordance.
RESUMO
Autoimmune phenomena including vasculitis are known to be associated with malignancy, especially those that are haematological in origin. Vasculitis syndromes associated with malignant disease include cutaneous leucocytoclastic vasculitis, polyarteritis nodosa, Churg-Strauss syndrome, microscopic polyangiitis, Wegener's granulomatosis and Henoch-Schönlein purpura. We describe a patient whose initial presentation with vasculitis led to the diagnosis of hairy cell leukaemia.
Assuntos
Neoplasias Hematológicas/complicações , Leucemia de Células Pilosas/complicações , Vasculite Leucocitoclástica Cutânea/etiologia , Vasculite/etiologia , Síndrome de Churg-Strauss/diagnóstico , Síndrome de Churg-Strauss/etiologia , Granulomatose com Poliangiite/diagnóstico , Granulomatose com Poliangiite/etiologia , Neoplasias Hematológicas/diagnóstico , Humanos , Vasculite por IgA/diagnóstico , Vasculite por IgA/etiologia , Leucemia de Células Pilosas/diagnóstico , Masculino , Poliangiite Microscópica/diagnóstico , Poliangiite Microscópica/etiologia , Pessoa de Meia-Idade , Poliarterite Nodosa/diagnóstico , Poliarterite Nodosa/etiologia , Vasculite/diagnóstico , Vasculite Leucocitoclástica Cutânea/diagnósticoRESUMO
Ducts of Luschka are a developmental abnormality found within the gallbladder fossa in up to 10% of cholecystectomy specimens. They are most often encountered by surgeons when injured during laparoscopic or open cholecystectomy, leading to bile leakage and subsequent peritonitis. Histologically, they are typically composed of lobular aggregates of small ductules lined by bland, cuboidal-to-columnar biliary-type epithelium, associated with centrally located, larger ductules surrounded by concentric fibrosis. We have identified 6 cases of florid Luschka duct proliferation in which the ductules demonstrated irregular growth pattern, loss of characteristic concentric fibrosis, and epithelial atypia that strongly suggested the diagnosis of invasive pancreatobiliary adenocarcinoma or metastatic adenocarcinoma involving the gallbladder serosa. Two of the cases were initially diagnosed as invasive adenocarcinoma, whereas the other 4 were sent for consultation to rule out adenocarcinoma. All cases were associated with marked acute and chronic cholecystitis with mucosal ulceration, cholelithiasis, and thickening of the gallbladder wall. The ducts of Luschka were located within the rim of adherent liver in all 6 cases and the gallbladder serosa in 5 cases. Limited follow-up information was available for all patients with no documentation of progressive disease. Awareness and proper recognition of the anatomic location and histologic features are imperative in distinguishing florid ducts of Luschka from both non-neoplastic conditions and most importantly adenocarcinoma.