Barton Kenney

Drug-induced thrombocytopenia.

Drug-induced thrombocytopenia was first described in the 19th century, yet our understanding of its pathogenesis continues to evolve. The list of drugs implicated in drug-induced thrombocytopenia is extensive and growing. Many, if not most, of these medications induce thrombocytopenia by immune mechanisms. Because the degree of thrombocytopenia can put patients at risk for serious bleeding, a prompt diagnosis is key to clinical management. The laboratory approach to diagnosing drug-induced thrombocytopenia is 2-pronged. First, nondrug causes of thrombocytopenia must be ruled out. Second, testing for drug-dependent platelet antibodies, available at specialized reference laboratories, often can identify the offending medication, although usually not in time for initial clinical management. Once a medication is suspected of causing thrombocytopenia, it must be discontinued promptly, and the patient should be monitored closely. Thrombocytopenia generally resolves quickly after offending medication withdrawal, and the prognosis of drug-induced thrombocytopenia is then excellent.

Primary malignant melanoma of the transverse colon: report of a case and review of the literature.

Gastrointestinal involvement by malignant melanoma is predominantly a metastatic phenomenon. Although primary malignant melanoma of the gastrointestinal tract has been documented in the esophagus, stomach, small bowel, and anorectum, the incidence of primary melanoma of the colon is rare and remains controversial in most cases. We present a case of solitary malignant melanoma of the transverse colon occurring in a 64-year-old African American male patient. Complete dermatologic and ophthalmologic examinations revealed no evidence of a cutaneous or an ocular primary lesion. Microscopic examination of the resection specimen revealed malignant melanoma, which was confirmed by immunohistochemical positivity for S100 and melan-A. We believe that this tumor represents a primary colonic malignant melanoma.

Diagnosis, Treatment, and Reporting of Adverse Effects of Transfusion

The risks of transfusion remain significant. Familiarity with the incidence, etiology, management, and prevention of commonly encountered transfusion reactions is integral to the practice of transfusion medicine. This review intends to serve as a practical guide reflecting the current understanding of adverse transfusion events, clinical features helpful for diagnosis, and recommended management strategies for typical scenarios. Severe and mild transfusion reactions are covered, with a focus on the distinguishing features of challenging clinical dilemmas. Topics include pulmonary complications of transfusion, hemolytic reactions, allergic and anaphylactic reactions, septic reactions, and febrile responses to transfusion. We also discuss a consultative approach to evaluation and reporting of transfusion reactions.

Central nervous system Aspergillus infection after epidural analgesia: diagnosis, therapeutic challenges, and literature review.

Aspergillus terreus was identified in an intradural spinal biopsy specimen from an African female with recurrent headache and hydrocephalus. Prior laboratory testing of cerebrospinal fluid was nondiagnostic, despite extensive central nervous system (CNS) involvement. CNS Aspergillus infection presents a diagnostic and therapeutic challenge and is reviewed in the context of this particularly instructive and difficult case.

Intermedin is overexpressed in hepatocellular carcinoma and regulates cell proliferation and survival

Angiogenesis is one of the hallmarks of tumor growth and metastasis. Identification of tumor angiogenic factors has been a critical component in understanding cancer biology and treatment. Intermedin (IMD) has been reported to promote angiogenesis in a rat ischemic model and human umbilical vascular endothelial cells. Our study sought to determine the role of IMD in human hepatocellular carcinoma tumor progression. High IMD mRNA expression levels were observed in human hepatocellular carcinoma tumors, even in early stage disease, by real‐time RT‐PCR. Immunohistochemical analysis of hepatocellular carcinoma clinical samples demonstrated that the tumor regions were significantly more immunoreactive for IMD than adjacent benign liver. Inhibition of IMD expression using RNA interference reduced cell proliferation in SK‐Hep‐1 and SNU‐398 cells. Blockage of IMD signaling using either an antagonist peptide or a neutralizing antibody inhibited growth in a dose‐dependent manner with concomitant induction of apoptosis, causing cleavage of caspase‐8 and downregulation of Gli1 and Bcl2. Conversely, addition of IMD active peptide increased the phosphorylation level of extracellular signal‐regulated kinase. Thus, IMD might play an important role in cell proliferation and survival of hepatocellular carcinoma. Our data suggests that IMD is a potential biomarker and therapeutic target for hepatocellular carcinoma. (Cancer Sci, doi: 10.1111/j.1349‐7006.2012.02341.x, 2012)

KRAS mutations are associated with specific morphologic features in colon cancer.

Background: Mutations in the KRAS gene occur at an early stage in the development of colorectal carcinoma. Importantly, KRAS mutation predicts resistance to anti-epidermal growth factor receptor therapy in stage IV disease. Goals: The aim of the current study is to correlate histologic features of colon cancer with the presence of KRAS mutations. Study: Tumor tissue from 145 colon cancer resections was tested for KRAS mutations. KRAS mutation status was correlated with demographic and histologic characteristics. Statistical analysis was performed using the Pearson &khgr;2 test and multivariate analysis. Results: KRAS mutations were present in 55/145 cases (37.9%), consistent with reported rates. KRAS mutations were significantly associated with usual adenocarcinoma morphology (multivariate P=0.014), peritumoral lymphocytic response (&khgr;2, P=0.028; multivariate P=0.017), T3-T4 status (&khgr;2, P=0.012; multivariate P=0.015), right-sided location (multivariate P=0.027), absence of lymphovascular invasion (multivariate P=0.008), and metastases at the time of resection (multivariate P=0.034). No association was found between KRAS mutation status and other factors. Conclusions: Specific morphologic features in colon cancer suggest a higher likelihood of the presence of KRAS mutations. These morphologic features overlap partially with those associated with DNA mismatch repair gene mutations. If confirmed, these results may suggest a paradigm for directed KRAS testing.

Acute vancomycin-dependent immune thrombocytopenia as an anamnestic response.

Drug-related thrombocytopenia is a well-described but relatively rare complication of antibiotic therapy. In this entity, platelet destruction is immune-mediated, often resulting in a precipitous drop in platelet count over a short period of time. Most of these cases of thrombocytopenia are drug-dependent, as discontinuation of the offending agent frequently results in a timely return to baseline, pre-exposure platelet levels. We report the case of a 61-year-old male patient receiving vancomycin and ceftazidime for lower extremity wet gangrene who experienced a marked, acute reduction in platelet count 12 to 15 hours after starting antibiotic therapy. There was no readily apparent clinical or laboratory explanation for his thrombocytopenia. Pre- and post- antibiotic serum samples were preserved and sent for drug-dependent platelet antibody analysis. The pre-exposure specimen revealed the presence of IgG vancomycin-dependent platelet antibodies, while the post-exposure specimen demonstrated both IgG and IgM vancomycin-dependent platelet antibodies. Ceftazidime-dependent platelet antibodies were not identified in either sample. These findings indicate prior sensitization to vancomycin, with subsequent acute production of IgM anti-platelet antibodies after re-exposure to the antibiotic. The patients antibiotics were held after the acute-onset of thrombocytopenia with subsequent restoration of normal platelet counts within 4 days of drug withdrawal, and the patient at no time experienced significant adverse bleeding events. Antibiotic therapy with vancomycin is a rare and perhaps overlooked cause for new-onset thrombocytopenia in hospitalized patients. This case illustrates that the development of severe thrombocytopenia within hours of vancomycin administration does not rule out drug-related immune clearance, as the rapid platelet destruction may indicate an anamnestic antibody response to the drug after previous exposure. In such a scenario, immediate discontinuation of vancomycin is recommended to improve platelet counts. From a laboratory perspective, retrieval of serum both pre- and post-administration of vancomycin is most helpful in determining a patients drug-immunization status and can help guide safe drug use during future infections.

Acinar Cell Carcinoma versus Solid Pseudopapillary Tumor of the Pancreas in Children: A Comparison of Two Rare and Overlapping Entities with Review of the Literature

Primary epithelial tumors of the pancreas are extremely uncommon in children, and among these, acinar cell carcinoma (ACC) is the most rare. Here we describe our recent observations in the case of a 10-year-old boy with one of these exceptional examples. The histologic diagnosis of ACC was supported by both immunohistochemistry and electron microscopy. Despite its rarity, ACC should be kept in the differential diagnosis of pediatric pancreatic exocrine tumors. We also provide a comparison with an example of solid pseudopapillary tumor, another relatively infrequent epithelial tumor of the pancreas in the young. We review the relevant literature addressing the clinical and pathologic features of ACC and its distinction from other pancreatic neoplasms.

Pseudointraductal papillary mucinous neoplasia caused by microscopic periductal endocrine tumors of the pancreas: a report of 3 cases.

Intraductal papillary mucinous neoplasms constitute histologically distinctive pancreatic tumors characterized by cystically dilated pancreatic ducts lined by papillary epithelium, often with extensive mucin production. With increasing awareness of and vigilance for these tumors, there has been a surge in the incidence of intraductal papillary mucinous neoplasms in the last few decades. However, resections of presumed intraductal papillary mucinous neoplasms sometimes reveal other types of cystic lesions. Here we describe 3 cases of small, incidentally identified pancreatic endocrine tumors that focally compressed the main pancreatic duct and presented clinically, radiologically, and grossly as intraductal papillary mucinous neoplasm. The histology of the dilated ducts in all cases lacked convincing features of intraductal papillary mucinous neoplasm, prompting more careful examination of the specimens and eventual identification of small well-differentiated endocrine neoplasms. The constellation of findings represented by pancreatic endocrine neoplasm-associated duct stricture and dilatation can mimic intraductal papillary mucinous neoplasm clinically and pathologically. Awareness of this phenomenon can potentially avoid misdiagnosis of intraductal papillary mucinous neoplasm in such cases.

DNA ploidy analysis as an adjunct for the detection of relapse in B-lineage acute lymphoblastic leukemia

Detection of relapse in acute lymphoblastic leukemia (ALL) is essential for proper management. However, immunophenotypic detection of relapse by flow cytometry in B-lineage ALL can be confounded by several factors, including lack of a unique immunophenotype and modulation of aberrant phenotypes after treatment. We hypothesized that flow cytometric DNA ploidy analysis may detect relapse in aneuploid ALL cases that might be missed by flow immunophenotyping. We retrospectively studied ALL cases at our institution between 1991 and 2003 (n = 114). Aneuploid populations were present at diagnosis in 32% of all patients. Sixty-five percent of all patients had “normal” leukemic immunophenotypes, defined as being similar to normal precursor B-cells, while 35% had “aberrant” immunophenotypes with myeloid or T antigen co-expression. In ALL cases that were originally aneuploid, follow-up ploidy-analysis detected relapsed disease in all cases which were also detected by flow immunophenotyping, suggesting that ploidy analysis is highly sensitive for detecting ALL relapse. However, in 5 cases in which the diagnosis of relapse could not be reliably made by flow immunophenotyping, ploidy analysis successfully detected aneuploid cells, i.e., relapse, in all five; these included 3 patients with normal and 2 with aberrant original immunophenotypes. These results suggest that it may be beneficial to perform ploidy analysis as an adjunct to flow immunophenotyping in following patients with B-lineage ALL who demonstrate aneuploidy at diagnosis.