Claudia P. Molina

Analysis of False-Negative Diagnoses on Endoscopic Brush Cytology of Biliary and Pancreatic Duct Strictures The Experience at 2 University Hospitals

CONTEXT Endoscopic brush cytology is a valuable technique for the diagnosis of pancreatobiliary malignancy. Despite its widespread use, the sensitivity of this method has been reported as approximately 50%. The specificity is usually higher than 95%. Few reports have systematically analyzed the reasons for this relatively low sensitivity. OBJECTIVES To determine the rate and reasons for false-negative diagnoses in endoscopic brushing cytology of biliary and pancreatic ducts based on the results of sensitivity, specificity, accuracy, and positive and negative predictive values. DESIGN Retrospective analysis of laboratory data and slide review of false-negative cases. SETTING Two tertiary care state university hospitals. PATIENTS A total of 183 pancreatobiliary brushing specimens obtained from patients undergoing endoscopic retrograde cholangiopancreatography for biliary or pancreatic duct disease for a 4- to 5-year period. INTERVENTION Endoscopic retrograde cholangiopancreatography brushings. MAIN OUTCOME MEASURES Determination of sensitivity, specificity, accuracy, and positive and negative predictive values. Analysis of false-negative results. RESULTS The sensitivity, specificity, accuracy, and positive and negative predictive values, overall, were 48%, 98%, 79%, 92%, and 76%, respectively. Sampling error was a major cause of false-negative diagnoses (67%), followed by interpretive (17%) and technical errors (17%). CONCLUSIONS Improvements in sensitivity and diagnostic accuracy for cancer of the pancreatobiliary tract can be achieved by optimizing slide preparatory techniques. Also, enhancement of the cytologists diagnostic skills enables the identification of the morphologic features of premalignant lesions. Repeat brushings are indicated for suspicious or negative results not consistent with the clinical or radiologic findings.

The pathologic spectrum of gastrointestinal and hepatic histoplasmosis

We characterized the pathologic spectrum of lesions in gastrointestinal and hepatic histoplasmosis by studying cases of disseminated disease in immunocompromised and immunocompetent patients from endemic and nonendemic areas. We evaluated 56 specimens from 52 patients with H&E and silver stains. Of these patients, 43% presented with gastrointestinal rather than pulmonary symptoms. Thirty-one percent had gastrointestinal lesions, 10% had liver lesions, and 43% had both. Gross gastrointestinal features included ulcers (49% of patients), nodules (21%), hemorrhage (13%), obstructive masses (6%) and normal mucosa (23%). Microscopic gastrointestinal findings included diffuse lymphohistiocytic infiltration (83%), ulceration (45%), lymphohistiocytic nodules (25%), or minimal inflammatory reaction (15%) but only rare well-formed granulomas (8.5%). The most common hepatic finding was portal lymphohistiocytic inflammation; discrete hepatic granulomas were seen in less than 20% of involved livers. The pathologist must be aware of the broad range of gastrointestinal and hepatic lesions produced by histoplasmosis and, in particular, that well-formed granulomas are rare. Given the appropriate clinical context, histoplasmosis should be considered in both immunocompetent and immunocompromised patients, regardless of pulmonary symptoms, in nonendemic as well as endemic areas.

Maporal Viral Infection in the Syrian Golden Hamster: A Model of Hantavirus Pulmonary Syndrome

Hantavirus pulmonary syndrome (HPS) is a severe and often fatal rodent-borne zoonosis. Maporal (MAP) virus is a newly discovered hantavirus that originally was isolated from an arboreal rice rat captured in central Venezuela. The results of this study indicate that MAP virus in the Syrian golden hamster (Mesocricetus auratus) can cause a disease that is clinically and pathologically remarkably similar to HPS. The similarities include the time course of clinical disease, presence of virus-specific IgG at the onset of clinical disease, subacute pneumonitis, rapid onset of diffuse alveolar edema in the absence of necrosis, hepatic-portal triaditis, mononuclear-cellular infiltrate in lung and liver, widespread distribution of hantaviral antigen in endothelial cells of the microvasculature of lung and other tissues, and variable lethality. These similarities suggest that the MAP virus-hamster system is a useful model for studies of the pathogenesis of HPS and for the evaluation of potential therapeutic agents.

Pathologic features of Mycobacterium kansasii infection in patients with acquired immunodeficiency syndrome.

CONTEXT Mycobacterium kansasii is a slow-growing photochromogenic mycobacterium that may infect patients with human immunodeficiency virus (HIV) late in the course of acquired immunodeficiency syndrome (AIDS). The clinical features of pulmonary and extrapulmonary infections have been described in the literature; however, the pathology of infection has not been adequately addressed. OBJECTIVE This report describes the pathologic features of 12 cases of M kansasii infection in patients with AIDS. DESIGN The medical records, autopsy protocols, cytologic material, and histologic material from patients with AIDS and concomitant M kansasii infection at a tertiary-care medical center during 1990-2001 were reviewed. RESULTS Twelve cases were identified, 6 by autopsy, 5 of which were diagnosed postmortem. Four of the 12 cases had cytologic material and 4 cases had histologic biopsies available for review. Pulmonary infection was most common (9/12), and all patients in whom thoracic lymph nodes were assessed showed involvement (7/7). Abdominal infection was less frequent, with only 1 of 6, 2 of 6, and 2 of 6, demonstrating liver, spleen, and abdominal lymph node infection, respectively. Isolated infections without documented pulmonary infection included brain abscess (n = 1), ulnar osteomyelitis (n = 1), and paratracheal mass (n = 1). Cytologic and histologic material showed a wide range of inflammatory reactions, including granulomas with and without necrosis, neutrophilic abscesses, spindle-cell proliferations, and foci of granular eosinophilic necrosis. The M kansasii bacillus was characteristically long, coarsely beaded, and frequently showed folded, bent, or curved ends. Intracellular bacilli were randomly or haphazardly distributed within histiocytes. CONCLUSION Mycobacterium kansasii infection produces predominantly pulmonary infection in late-stage AIDS with a high incidence of thoracic lymph node involvement and a much lower incidence of dissemination to other sites. Infection is manifest as a wide variety of inflammatory reactions on cytology and histology; however, the characteristic appearance of the bacillus on acid-fast bacilli stain and its intracellular arrangement in histiocytes can allow a presumptive identification.

Microcystic adenoma of the pancreas: Cytologic appearance on percutaneous and endoscopic ultrasound-guided fine-needle aspiration: Report of a case

Microcystic adenoma is an uncommon neoplasm of the pancreas usually affecting older people. Its histologic features have been well characterized. The cytologic appearance of this tumor has been described only rarely, however. Microcystic adenomas may enlarge considerably and often produce symptoms related to their compression to adjacent anatomic structures. The fact that this neoplasm is almost always benign indicates the need for accurate preoperative diagnosis to differentiate it from other, more common, malignant or potentially malignant tumors of the pancreas. We present a case of pancreatic microcystic adenoma initially diagnosed by percutaneous image‐guided fine‐needle aspiration cytologic examination and core biopsy and further evaluated by endoscopic ultrasound‐guided fine‐needle aspiration on follow‐up. This case report illustrates that microcystic adenoma of the pancreas can be accurately diagnosed by aspiration cytology. Fine‐needle aspiration—percutaneous, guided by computerized tomography, or endoscopically guided by ultrasonography—constitutes a reliable and cost‐efficient diagnostic tool associated with minimal trauma to the patient. Diagn. Cytopathol. 1998;20:298–301.

Marked Increase in L-Selectin-Negative T Cells in Neonatal Pertussis The Lymphocytosis Explained?

The detailed immunophenotype of peripheral blood lymphocytes from a neonate with pertussis was determined by flow cytometry and compared with results from cord blood from healthy newborns. Most (72%) of the lymphocytes were CD3+ T cells with a normal CD4/CD8 ratio (2.5). The T cells were largely HLA-DR negative and CD45RA+, consistent with unstimulated naïve T cells. Almost all of the CD4+ T cells were Leu8 (L-selectin, CD62L) negative, while almost all of the CD8+ T cells were CD28+. There was no increase in CD7- CD4+ T cells (Th2-like). No relative increase in CD16/56+ NK cells (5%) or CD19/20+ B cells was seen. The most dramatic finding in this case was the remarkable lack of expression of L-selectin by the T cells. L-selectin expression is associated with homing of peripheral blood lymphocytes to lymph nodes. The dramatic reduction in L-selectin expression of the T lymphocytes in pertussis, perhaps induced by pertussis toxin, likely prevents homing of the T cells to peripheral lymphoid tissues and provides a likely explanation for the marked lymphocytosis noted in this disease.

Pathology of Black Creek Canal virus infection in juvenile hispid cotton rats (Sigmodon hispidus)

The purpose of this study was to assess the effect of inoculum dose on the pathogenesis of Black Creek Canal virus (BCCV) infection in the hispid cotton rat (Sigmodon hispidus), the principal host of BCCV. No sign of illness was observed in any of the 52 juvenile hispid cotton rats inoculated with 3.1, 1.1, -0.9, or -2.9 log(10) median infectious doses(VeroE6) (ID(50-VeroE6)) of BCCV and euthanized on day 9, 18, 27, or 54 postinoculation (PI). Analysis of virus assay and serological data indicated that inoculum dose could significantly affect the pathogenesis of BCCV infection in juvenile hispid cotton rats. For example, the six animals inoculated with 3.1 or 1.1 log(10) ID(50-VeroE6) and euthanized on day 54 PI were virus positive and antibody positive, whereas the six animals inoculated with -0.9 or -2.9 log(10) ID(50-VeroE6) and euthanized on day 54 PI were virus positive but antibody negative. Microscopic examination of tissues from the animals inoculated with 3.1 or 1.1 log(10) ID(50-VeroE6) revealed diffuse, subacute pneumonitis in the lungs of all the animals euthanized on day 18 PI or thereafter, and indicated that the severity of pneumonitis was dependent upon inoculum dose as well as duration of infection (i.e., amount of time elapsed since inoculation).

Cytodiagnosis in the Autopsy Suite: A Tool for Improving Autopsy Quality and Resident Education

CONTEXT Despite several publications attesting to its accuracy and value, cytology is rarely used for preliminary autopsy diagnosis in the United States. Postmortem cytodiagnosis has the potential to increase the accuracy and specificity of the provisional and final autopsy diagnoses, increase resident interest in cytodiagnostic techniques, and direct pathologists to request pertinent special studies, such as microbial cultures and special stains. OBJECTIVE To assess and illustrate the value of cytodiagnostic techniques for improving autopsy quality assurance and resident education. DESIGN Eighty-five samples were evaluated from 49 nonconsecutive autopsies. Sixty-five focal lesions were sampled by direct scraping. Diffuse lung consolidation was sampled by fine-needle aspiration (20 samples). Smears and cytocentrifuge preparations of fine-needle aspirations were routinely stained by both Papanicolaou and Romanowski methods. Cytologic diagnoses were compared with final autopsy diagnoses, and both cytology and pertinent histology were reviewed. RESULTS Clinical or radiographic antemortem site-specific diagnoses had been made in 28 (33%) of the 85 samples. A definite diagnosis was made by postmortem cytology in 68 (80%) of 85 samples, and these diagnoses could contribute to provisional autopsy diagnosis in 46 instances (68%). Resident and faculty enthusiasm for the use of cytology in the autopsy suite has increased during the 7 years following the study. Case examples illustrating the benefits of postmortem cytology are provided. CONCLUSIONS Postmortem cytology benefits both autopsy quality and resident education.

Expression of CD4 on peripheral blood granulocytes: a novel finding in a case of myelodysplastic syndrome in association with t(5;12)

Myelodysplastic syndromes (MDS) are associated with cell maturation defects that can manifest as abnormal surface antigen expression. We describe a patient with refractory anemia with excess blasts, who presented with infection and extensive dysplastic features in peripheral blood granulocytes. The granulocytes expressed CD11b, CD13, CD15, CD33, and CD43. The granulocytes also expressed CD4 antigen. Cytogenetic analysis showed a clonal t(5;12)(q33;p13). The patient improved on antibiotics with partial improvement in the dysplastic features. However, shortly after, the patient experienced paravertebral extramedullary blast transformation followed by a leukemia phase of acute monoblastic leukemia. The patient died a few days later. This is the first report describing anomalous expression of CD4 on granulocytes in MDS. Since the breakpoint on chromosome 12 is near the CD4 gene, which is mapped to 12p12, we hypothesize that dysregulation of the CD4 gene may have occurred resulting in its persistent expression on mature and maturing granulocytes.

Diagnosis of recurrent uterine carcinosarcoma by fine‐needle aspiration cytology: Report of a case

Uterine carcinosarcomas are uncommon, aggressive neoplasms usually afflicting postmenopausal women. Histologically, they are characterized by the presence of both malignant epithelial and stromal cells. The latter may be either homologous or heterologous in nature. The cytologic diagnosis of carcinosarcoma via fine‐needle aspiration (FNA) was previously described for primary tumors arising in the parotid gland, breast, lung, and ovary. Although the diagnosis of uterine carcinosarcoma via cervicovaginal, endometrial, and peritoneal fluid cytology has been described, the FNA cytology diagnosis of recurrent uterine carcinosarcoma has only been rarely described. We present a case of recurrent uterine carcinosarcoma in a 59‐yr‐old woman, diagnosed by ultrasound‐guided FNA cytology. Cytologic smears showed a biphasic neoplasm consisting of both malignant columnar epithelial and spindle cells, in a background of tumor diathesis. This case illustrates the diagnostic utility of aspiration cytology in the investigation of recurrent carcinosarcoma in clinically suspicious lesions arising postsurgery. Diagn. Cytopathol. 23:108–113, 2000.