Post-treatment bacterial endocarditis mimicking fungal organisms: a morphologic comparison and tips for avoiding this diagnostic pitfall.

BACKGROUND: Histopathologic differentiation of bacterial endocarditis from yeast-like fungal endocarditis is usually straightforward; however, an underappreciated phenomenon is the effect of antimicrobial therapy on bacterial size, shape and septa (cross-wall) formation resulting in bacterial forms that mimic yeast-like fungi. In this article we illustrate the alterations that occur in antibiotic-treated Staphylococcus aureus endocarditis and compare these changes to histopathologic findings in unaltered S. aureus and Histoplasma endocarditis, respectively. METHODS: Resected valves from three cases of endocarditis were compared based on the type ofinflammatory reaction, organism morphology and culture results. Case 1 was S. aureus endocarditis initially misclassified as Histoplasma due to its atypical morphologic and histopathologic features. The two cases included for comparison were an S. aureus endocarditis with more classic features and an Histoplasma capsulatum endocarditis. Hematoxylin and eosin (H&E), Gram, periodic acid Schiff (PAS), Gomori-Grocott methenamine silver stains (GMS), and culture results were compared in all cases. Molecular and immunohistochemistry tests were used for confirmation of first case. High power oil-immersion was used to visualize organisms' characteristics in all three cases. RESULTS: Case 1 and Case 3 (Histoplasma-infected valves) had fibrinous exudates with scattered macrophages. The microorganisms observed in the first case of methicillin-sensitive S. aureus (MSSA) were ∼ 2-3 µm by GMS stain and had prominent septations. Histoplasma yeast were round to oval, ∼ 3-4 µm in size and demonstrated budding. S. aureus without alterations were round, ∼ 1 µm in size, and lacked prominent septations. Necrotizing purulent inflammation was present in the unaltered case of MSSA. The MSSA case with alterations from antibiotic treatment did not stain well with the Gram stain and organisms were best visualized with the PAS and GMS stains. CONCLUSIONS: Antibiotic therapy for bacterial endocarditis can alter the inflammatory reaction to infection, bacterial size, septa formation, and staining characteristics. Knowledge of these therapy-related effects and use of high-power magnification helps to avoid misclassification as yeast-like fungi.

Salivary gland fine-needle aspiration cytology with the application of the Milan system for risk stratification and histological correlation: A retrospective 6-year study.

BACKGROUND: The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) is based on risk stratification. We presented our experience with fine-needle aspiration cytology (FNAC) for the diagnosis of salivary glands lesions by applying the MSRSGC categorization to the cytological diagnoses, and determined risk of malignancy (ROM) for each category. METHODS: Fine-needle aspiration cytology of salivary gland lesions performed over a 6-year period was retrieved. FNAC results were retrospectively categorized according to the MSRSGC criteria, and correlated with corresponding histologic follow-up. ROM for each diagnostic category was calculated. RESULTS: A total of 208 FNAC of salivary gland lesions were reviewed and retrospectively categorized as: non-diagnostic (ND) 23 (11%), non-neoplastic (NN) 54 (26%), atypia of undetermined significance (AUS) 10 (4.8%), benign neoplasms (BN) 77 (37%), salivary gland of uncertain malignant potential (SUMP) 13 (6.3%), suspicious for malignancy (SM) 7 (3.4%), and malignant (M) 24 (11.5%). Histopathological follow-up was available for 84 of 208 cases (40.4%). Overall concordance rate between FNAC and histology was 78.8%. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated as 93.3%, 94.6%, 82.4%, and 98.2%, respectively. Diagnostic accuracy to distinguish benign from malignant disease was 94.4%. ROM for each category was ND 0%, NN 0%, AUS 75%, BN 2.2%, SUMP 28.6%, SM 50%, and M 100%. CONCLUSION: Fine-needle aspiration cytology continues to be an accurate diagnostic tool for most salivary gland neoplasms showing classical morphologic features. However, difficult cases with unusual or overlapping features will occur. In these situations, the use of MSRSGC risk-stratification could be helpful to define appropriate management.

Gamna-Gandy bodies in fine-needle aspiration from abdominal splenosis: A clue to underlying portal hypertension.

A 40-year-old woman presented with abdominal pain and jaundice. Past medical history was significant only for splenectomy following a motor vehicle accident. Owing to presence of multiple peritoneal nodules on computerized tomography (CT) and elevated serum CA-125, ovarian peritoneal carcinomatosis was suspected. Ultrasound-guided fine-needle aspiration (FNA) revealed presence of abundant hemosiderin, leukocytes, endothelial cells, and fungal hypha-like structures. No evidence of neoplasia was found. Findings were consistent with Gamna-Gandy bodies (GGBS) within splenic tissue. Based on history of splenectomy and FNA findings, a diagnosis of abdominal splenosis with presence of GGBS was made. Workup for hepatic cirrhosis and portal hypertension was recommended. Liver biopsy confirmed presence of cirrhosis. To our knowledge, this is the first report of GGBS identified within abdominal splenosis. It is important for pathologists to be able to recognize GGBS and to be aware of their relationship to portal hypertension and other conditions associated with severe vascular congestion or hemorrhage. History and pathogenesis of GGBS, their diagnostic morphologic features and a review of cases of GGBS diagnosed via cytology are given.

Correlation of microbiologic culture and fine-needle aspiration cytology: A 14-year experience at a single institution.

BACKGROUND: Fine-needle aspiration (FNA) is an important tool for the diagnosis of infectious disease. FNA material should be appropriately submitted for cultures when indicated by preliminary findings. Correlation of cytologic diagnoses with culture results are important quality assurance tools. The current study reviewed 14 years of FNA-culture correlation. METHODS: FNA cytology-culture correlation records from the years 1996 through 2007 and 2010 through 2011 were retrieved from electronic databases compiled for histology and culture correlation. Correlation was limited to those cases for which material was submitted for culture from the FNA sample. Culture results were retrieved from the laboratory or hospital information system. RESULTS: Correlative data included 770 cases. Cytology, culture, or both were positive for microbes in 416 of 770 samples (54%), excluding cultured bacterial skin contaminants. Among the 204 bacteria cases, 93 (46%) were identified by cytology and culture, 92 (45%) were identified by culture only, and 19 (9%) were identified by cytology only. Among the 16 cases of Actinomycetales, 8 (50%) were identified by cytology and culture, 5 (31%) were identified by culture only, and 3 (19%) were identified by cytology only. Of the 129 cases of mycobacteria, 63 (49%) were identified by cytology and culture, 44 (34%) were identified by culture only, and 22 (17%) were identified by cytology only. Among the 67 cases of fungi, 34 (51%) were identified by cytology only, with 15 of these 34 cases being fungal hyphae; 25 cases (37%) were identified by cytology and culture, with a 100% concordance between the cytology diagnosis and culture result; and 8 cases (12%) were identified by culture only. CONCLUSIONS: FNA cytology-culture correlation is a valuable tool with which to assess the efficacy and limitations of the direct diagnosis of infectious agents, and to identify types of infections that may be negative on culture but positive on cytology diagnosis.

Should high-risk adolescents have Papanicolaou tests?

BACKGROUND: The current American College of Obstetricians and Gynecologists guidelines state that cervical cancer screening should begin at age 21 years, regardless of sexual or obstetric history. However, previous studies have demonstrated that there is a small but significant subset of high-risk adolescents with extensive sexual and obstetric history who harbor a significant squamous cervical lesion. The objective of the current study was to use histologic and demographic data from adolescents (aged <21 years) who received Papanicolaou (Pap) tests to determine whether they benefited from early cervical cancer screening. METHODS: Adolescent girls who had Pap tests between 2000 and 2010 were included in the study. Demographic data, including obstetric history, number of sexual partners, age of first coitus, age at first pregnancy, menarche, smoking history, and Chlamydia and syphilis infection, were analyzed for associations with levels of cervical dysplasia. RESULTS: Of 56,785 adolescent Pap tests, 277 (0.5%) were diagnosed as high-grade squamous HSIL, and 56 of those Pap tests (20%) were from patients who had grade 3 cervical intraepithelial neoplasia (CIN-3) on subsequent biopsy and/or excision. One patient had microinvasive cervical carcinoma identified on loop electrosurgical excision procedure at age 27 years after an HSIL Pap test. Increased parity was associated significantly with higher rates of CIN-3. CONCLUSIONS: The study findings indicated that current American College of Obstetricians and Gynecologists guidelines to begin Pap testing at age 21 years are appropriate for the majority of adolescents, because the rate of HSIL is very low, and the risk for invasive carcinoma is minimal. Although higher parity was associated with a significantly increased grade of CIN, the conclusions are questionable because of the significant amount of missing demographic data points. That being said, this study should lead to other similar studies to determine any association of higher grade CIN with adolescent sexual and obstetric history.

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.

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.

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.

Role of FNA cytology and immunochemistry in the diagnosis and management of medullary thyroid carcinoma: report of six cases and review of the literature.

Medullary thyroid carcinoma (MTC) is a rare neuroendocrine thyroid malignancy. This study retrospectively reviewed 10 fine-needle aspiration samples from six MTC patients. Aspirated specimens were from thyroid (3), cervical lymph nodes (5), left lung (1), and anterior chest wall (1). Cytomorphology consisted predominantly of plasmacytoid cells (3 cases), spindle cells (2 cases), and epithelioid cells (1 case). However, all specimens had a mixture of other cell types and "salt and pepper" chromatin. Only one specimen showed Congo-red-positive amyloid. Calcitonin was expressed in 7/7 specimens. Four patients underwent surgical excision and MTC was confirmed in all four. Follow-up studies included serum calcitonin (3/6 cases) and imaging (2/6 cases). One patient had MTC associated with multiple endocrine neoplasia IIA syndrome and one had familial MTC with a history of MTC in mother. In conclusion, the cytomorphology of MTC is typical and calcitonin immunostain is a reliable method for confirming primary or metastatic MTC. Early cytological diagnosis of MTC positively impacted patient management. Follow-up with serum calcitonin and imaging is helpful in the early detection of recurrences.

Fatal reactive hemophagocytosis related to disseminated histoplasmosis with endocarditis: an unusual case diagnosed at autopsy.

Reactive hemophagocytic syndrome (RHS) is an uncommon life-threatening disorder. It is believed to be caused by widespread non-neoplastic proliferation and inappropriate activation of mature macrophages, resulting in excessive cytokine activation which leads to hematophagocytosis by cells of the macrophage-monocyte lineage and multiorgan dysfunction. RHS may be associated with infections caused by bacterial, viral and fungal organisms as well as lymphoproliferative disorders, nonhematopoietic malignancies, autoimmune diseases and some therapeutic drugs. Immunosuppression is a frequent underlying condition in RHS. The following case presentation describes a patient with a history of chronic hepatitis C, cryoglobulinemia, renal failure and Staphylococcus aureus perinephric abscess and bacteremia, who, at autopsy, was found to have disseminated histoplasmosis with fungal endocarditis and RHS.

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. STUDY DESIGN: Retrospective case study and literature review. METHODS: Published reports of branchial cleft carcinomas were reviewed in conjunction with a unique case presenting at the University of Texas Medical Branch (Galveston, TX). RESULTS: Most cases of branchial cleft carcinomas are probably cystic metastases from head and neck primary sites. Cutaneous involvement with primary branchial cleft carcinomas is rare but may occur in recurrent lesions. CONCLUSIONS: The diagnosis of a primary branchial cleft cyst carcinoma requires the fulfillment of strict criteria. Cystic metastases from head and neck primaries can mimic branchial cleft carcinomas histologically. Correct diagnosis is important so that appropriate surgical and radiotherapeutic treatment can be delivered.