Vicki J. Schnadig

Fine‐needle aspiration of thyroid nodules: A study of 4703 patients with histologic and clinical correlations

The Papanicolaou Society of Cytopathology recently proposed 6 diagnostic categories for the classification of thyroid fine‐needle aspiration (FNA) cytology. Using these categories, the experience with FNA from 2 institutions was studied with emphasis on cytologic‐histologic correlation, source of errors, and clinical management.

Monitoring of BK Viral Load in Renal Allograft Recipients by Real-Time PCR Assays

BK virus (BKV) is a nonenveloped, double-stranded DNA virus of the polyomavirus family that primarily affects immunocompromised people. BKV may cause nephropathy in renal transplant recipients receiving immunosuppressive therapy, resulting in renal dysfunction and, possibly, graft loss. Monitoring of BK viral load in urine and blood has been used as a surrogate marker of BKV nephropathy (BKVN). Although real-time polymerase chain reaction (PCR) is the method of choice, currently there is no US Food and Drug Administration-approved or standardized BK viral load assay. Different PCR assays vary significantly in sample types, DNA extraction method, PCR primers and probes, and reference materials used to generate a standard curve. These differences can affect the accuracy, specificity, and dynamic ranges of various real-time PCR assays. These analytic differences cause difficulty in comparing test results, making it impossible to establish universal standardized cutoff values that correlate with clinical manifestations of BKVN. In this review, we summarize real-time PCR assays used for managing BKVN.

Clinical and pathologic features of Mycobacterium fortuitum infections. An emerging pathogen in patients with AIDS.

The clinical and pathologic features of Mycobacterium fortuitum infection in 11 patients with AIDS were characterized. Nine patients had cervical lymphadenitis; 2 had disseminated infection. The infection occurred late in the course of AIDS, and the only laboratory abnormality seen in more than half of patients (7/11) was relative monocytosis. Absolute monocytosis also was seen in 4 of 11 patients. In both cytologic and histologic preparations, the inflammatory pattern was suppurative with necrosis or a mixed suppurative-granulomatous reaction. M fortuitum, a thin, branching bacillus, stained inconsistently in direct smear and histologic preparations. Staining was variable with Gram, auramine, Brown-Hopps, Gram-Weigert, Kinyoun, Ziehl-Neelsen, modified Kinyoun, and Fite stains. Organisms, when present, were always seen in areas of suppurative inflammation. Incorrect presumptive diagnosis, based on misinterpretation of clinical signs and symptoms or on erroneous identification of M fortuitum bacilli as Nocardia species, led to a delay in proper therapy for 7 of 11 patients. Definitive therapy after culture identification resulted in complete resolution of infection in all patients except 1.

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.

Cystic metastasis versus branchial cleft carcinoma: a diagnostic challenge.

Objectives There is controversy regarding the existence of branchial cleft carcinomas. The objectives are to familiarize the clinician with the presentation and treatment of cystic metastases from head and neck primary sites and differentiate these from primary branchial cleft cyst carcinomas.

Giving new life to old lungs: methods to produce and assess whole human paediatric bioengineered lungs.

We report, for the first time, the development of an organ culture system and protocols to support recellularization of whole acellular (AC) human paediatric lung scaffolds. The protocol for paediatric lung recellularization was developed using human transformed or immortalized cell lines and single human AC lung scaffolds. Using these surrogate cell populations, we identified cell number requirements, cell type and order of cell installations, flow rates and bioreactor management methods necessary for bioengineering whole lungs. Following the development of appropriate cell installation protocols, paediatric AC scaffolds were recellularized using primary lung alveolar epithelial cells (AECs), vascular cells and tracheal/bronchial cells isolated from discarded human adult lungs. Bioengineered paediatric lungs were shown to contain well‐developed vascular, respiratory epithelial and lung tissue, with evidence of alveolar–capillary junction formation. Types I and II AECs were found thoughout the paediatric lungs. Furthermore, surfactant protein‐C and ‐D and collagen I were produced in the bioengineered lungs, which resulted in normal lung compliance measurements. Although this is a first step in the process of developing tissues for transplantation, this study demonstrates the feasibility of producing bioengineered lungs for clinical use. Copyright

Disseminated Histoplasma capsulatum infection presenting as genital ulcerations.

Background Histoplasma capsulatum infection in adults is most often subclinical but can result in disseminated disease with weight loss, fever, hepatosplenomegaly, and oropharyngeal ulcerations. Genital ulceration as the presenting sign of the disease has been reported rarely. Case A 63-year-old woman presented with multiple vaginal ulcerations due to chronic disseminated H capsulatum infection. Initial diagnosis was made by Papanicolaou and Giemsa-stained vulvar smears. Ketoconazole therapy resulted in clearing of the lesions in 5 weeks. Conclusion Chronic disseminated histoplasmosis is an insidious and potentially fatal disease that can present rarely as genital mucocutaneous ulcerations in women. Prompt presumptive diagnosis can be accomplished by examination of smears obtained by ulcer abrasion, permitting institution of appropriate therapy.

Fine needle aspiration diagnosis of necrotizing eosinophilic abscess clinically mimicking hepatic neoplasia: a case report.

BACKGROUND Eosinophilic hepatic pseudotumors (EHP) are known complications of visceral larva migrans (VLM). By radiologic studies, EHP can be suspicious for primary or metastatic hepatic neoplasia. Diagnosis of an EHP by fine needle aspiration (FNA) led to the diagnosis of Toxocara VLM in a patient with suspected hepatic neoplasia. CASE REPORT A 38-year-old Cambodian man had hepatitis B and chronic hepatitis with grade III portal fibrosis diagnosed in 2003. He had had negative routine alpha-fetoprotein and radiologic screening for hepatic neoplasia until 2006 when abdominal computed tomography revealed a 1.6 x 1.2-cm, ill-defined hypodense lesion in segment VII. Biopsy was recommended in order to exclude hepatocellular carcinoma. FNA of the lesion contained abundant Charcot-Leyden crystals, degenerating eosinophils and necrotic debris. Work-up for nematode larva migrans was recommended. Toxocara antigen IgG titer was significantly elevated leading to a presumptive diagnosis of VLM, and therapy for Toxocara-induced VLM was given. CONCLUSION Identification of abundant Charcot-Leyden crystals and necrotic eosinophils in an FNA of the liver led to appropriate ancillary diagnostic tests and therapy for visceral larva migrans.

Bone metastasis in epithelial ovarian carcinoma

Two cases of bone metastasis in patients with epithelial ovarian carcinoma and a review of the literature are presented. Bone metastases detected antemortem are rare and herald a poor prognosis.

Is fine needle aspiration cytology a useful diagnostic tool for granular cell tumors? A cytohistological review with emphasis on pitfalls.

Background: Granular cell tumors (GCT) formerly known as Abrikossoff tumor or granular cell myoblastoma, are rare neoplasms encountered in the fine needle aspiration (FNA) service. Named because of their highly granular cytoplasm which is invariably positive for the S-100 antibody, the classic GCT is thought to be of neural origin. The cytomorphological features range from highly cellular to scanty cellular smears with dispersed polygonal tumor cells. The cells have abundant eosinophilic granular cytoplasm, eccentric round to oval vesicular nuclei with small inconspicuous nucleoli. The fragility of the cells can result in many stripped nuclei in a granular background. The differential diagnosis occasionally can range from a benign or reactive process to features that are suspicious for malignancy. Some of the concerning cytologic features include necrosis, mitoses and nuclear pleomorphism. Methods: We identified 6 cases of suspected GCT on cytology within the last 10 years and compared them to their final histologic diagnoses. Results: Four had histologic correlation of GCT including one case that was suspicious for GCT on cytology and called atypical with features concerning for a malignant neoplasm. Of the other two cases where GCT was suspected, one showed breast tissue with fibrocystic changes, and the other was a Hurthle cell adenoma of the thyroid. Conclusions: These results imply that FNA has utility in the diagnosis of GCT, and should be included in the differential diagnoses when cells with abundant granular cytoplasm are seen on cytology. Careful attention to cytologic atypia, signs of reactive changes, use of immunohistochemistry, and clinical correlation are helpful in arriving at a definite diagnosis on FNA cytology.