Loss of heterozygosity analysis to diagnose adrenal cortical carcinoma: are we there yet?
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Publications and source records attributed to E Greenebaum.
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BACKGROUND: The head and neck region is one of the most common locations of rhabdomyosarcoma. Salivary gland involvement is usually secondary to advanced disease, and presentation as a primary salivary gland tumor is very rare. METHODS: Three cases of rhabdomyosarcoma presenting as parotid masses, in 2 boys (ages 3 and 7 years) and a girl (age 5 years), were retrieved from the files of 2 institutions. RESULTS: The three patients presented with parotid gland enlargement. Clinically, the enlargements appeared to be inflammatory, and they were treated unsuccessfully with antibiotics. Fine-needle aspiration biopsy (FNAB) was performed on all three patients. The cytologic features varied from one case to another; one case had features of a small round cell tumor, another was composed of a monomorphic population of spindle cells in a metachromatic stroma, and the third case was composed mostly of spindle cells with moderate cellular pleomorphism. Immunohistochemical studies performed in two of the cases confirmed the diagnosis of rhabdomyosarcoma, and ultrastructural studies were confirmatory in the other case. The patients are alive; 2 of them have had no evidence of disease after 6 and 9 years of follow-up, and the third, the most recent patient, has just finished adjuvant chemotherapy. CONCLUSIONS: With the increased use of FNAB for the evaluation of salivary gland masses in children, the authors believe that it is important to recognize the occurrence of rhabdomyosarcoma in this location. Immunohistochemical studies have proved helpful in differentiating rhabdomyosarcoma from other parotid gland tumors and can be readily done on cytologic preparations.
Adenovirus (ADV) is increasingly recognized as a cause of morbidity and mortality in transplant recipients, but ADV pneumonitis has rarely been reported after lung transplantation. The few reported instances of ADV pneumonitis occurred mostly in children immediately after lung transplantation suggesting "primary" infection. We report a fatal case of ADV pneumonitis occurring in an adult, 4 years after unilateral lung transplantation, in whom the premortem diagnosis was not determined. Autopsy revealed severe necrotizing bronchitis, bronchiolitis, and interstitial pneumonitis. Characteristic smudgy intranuclear inclusions, immunohistochemistry for viral protein, in situ hybridization for viral genome, and postmortem lung cultures established ADV as the etiologic agent. ADV can cause fatal, occult respiratory infection in adult lung transplant recipients, remote from transplant surgery.
To determine the origin and nature of mucinlike material in fine-needle aspiration (FNA) smears of the breast in noncancerous breast lesions, we studied breast FNA smears from four patients. All smears contained epithelial cells floating in a mucinlike background, which raised suspicion for mucinous (colloid) carcinoma. Mucicarmine stain was performed on one smear from each case. Subsequent tissue biopsy specimens were studied using mucicarmine, periodic acid-Schiff with and without diastase, and alcian blue stains at pH 2.7 and 0.9 on selected tissue sections. Correlation of the cytologic and histologic findings of each lesion was performed. The mucinlike background in all four FNA smears stained strongly with mucicarmine. Corresponding biopsy specimens revealed pseudoangiomatous hyperplasia in the first case, fibroadenoma and atypical ductal hyperplasia in the second, benign phyllodes tumor in the third, and fibroadenoma in the fourth. Each lesion in cases 1 to 3 was associated closely with fibrocystic changes. In case 4, cystic changes were located within the fibroadenoma. On tissue sections of all four cases, the cyst contents and 10% to 50% of normal lobule and duct contents stained with mucicarmine, indicating that the cyst contents were the most probable source of mucin in the FNA smears. The presence of pools of mucicarmine-positive material in FNA smears of the breast is not an exclusive feature of mucinous carcinoma; mucicarmine-positive mucin can arise from benign cystic changes as well as from normal lobules and ducts.
A neural net-based, semiautomated, interactive computerized cell analysis system (The PAPNET system, Neuromedical Systems, Suffern, NY) was used to examine cells from 138 esophageal smears obtained by lavage, brushings, or balloon from as many patients. From each smear, trained human observers examined 128 cell images selected by the machine. Abnormal cells were identified in all 35 patients with cancer, whether esophageal, gastric, oral, or metastatic. Further, in 11 smears, the displayed images allowed the recognition of effects of radiotherapy and, in 14 smears, the diagnosis of a specific tumor type, such as squamous cell carcinoma (8 patients) or adenocarcinoma (6 patients). In 3 additional cases, the diagnosis of "carcinoma, not further specified," was established. One case of esophageal carcinoma in situ, not previously recognized on a smear or in the biopsy specimen, and one case of gastric adenocarcinoma, not recognized in the smear, were identified in PAPNET-generated images. The possible application of the apparatus to the triage of smears and population screening for esophageal and gastric carcinoma precursors is discussed.
Cytologic evaluation of second trimester amniotic fluid (AF) is a rapid, inexpensive adjunct to prenatal diagnosis of open neural tube defects (ONTDs). Our goal was to determine whether the neural-appearing cells and/or large foamy macrophages in the AF of anencephalics are indeed of neural and/or glial origin. In two second trimester patients with elevated serum alpha-fetoprotein (AFP) and polyhydramnios, fetal sonogram studies showed anencephaly; amniocentesis was performed for AF-AFP, cytogenetic, and cytologic studies. AF sediment smears were initially Papanicolaou-stained; next, the same smears were immunoperoxidase (IP)-stained for glial fibrillary acidic protein (GFAP). If GFAP negative, slides were restained for synaptophysin (SYN) and neuron-specific enolase (NSE). Both AFs contained small neural-appearing cells (5-10 microns) singly and in clusters, with dense, round, homogeneous nuclei, an occasional nucleolus, and scant cytoplasmic rim. These were GFAP negative and SYN and NSE positive; the large vacuolated, lipid-laden macrophages (20-40 microns) were negative for all three IP stains. In conclusion, positive IP staining for SYN and NSE supports the morphologic impression that small dark cells in AF are of neural origin, while negative IP staining of large foamy macrophages suggests nonneural, nonglial origin.
Using fluoroscopic guidance, polyethylene biliary stents are replaced endoscopically or percutaneously when bile duct stenosis recurs. To improve the sensitivity of conventional biliary cytology, we examined cells recovered from removed stents. Biliary stents removed endoscopically from each of 11 patients were rinsed with saline; next, the rinse was centrifuged and the sediment smeared and Papanicolaou stained. Three patients with choledocholithiasis had biliary stent replacement cytology (BSRC) to exclude a neoplastic etiology. Eight patients with clinicoradiologic evidence of hepatobiliary or pancreatic carcinoma had BSRCs performed for pathologic documentation of carcinoma. BSRC from six of eight patients with clinicoradiologically malignant biliary strictures contained malignant cells, predominantly in loose clusters, but also singly (sensitivity 75%, specificity 100%; positive predictive value 75%, negative predicative value 60%). Reparative epithelial atypia was also present in all cases. BSRC from two patients with clinicoradiological evidence of carcinoma of the biliary region and from three with choledocholithiasis contained only bile pigment, leukocytes, and benign epithelial cells. The sampling of cells which have accumulated on, or in biliary stents, improves the sensitivity of biliary cytology. This is most applicable when 1) a patient is inoperable, 2) tissue biopsy is neither feasible nor diagnostic, 3) prior brush, suction, percutaneous, or endoscopic needle aspiration cytology is inconclusive, and 4) permanent metal stent is needed.
Enterogenous cyst is a benign lesion derived from misplaced endodermal epithelium. We report the aspiration cytology findings of an orbital cyst from a 32-year-old woman. The smears contain benign-appearing cuboidal glandular cells with focal mucinous features. Carcinoembryonic antigen level in the cyst fluid was markedly elevated. These findings are consistent with recurrence of the enterogenous cyst initially diagnosed 7 years earlier.
The Orphan Annie-eyed clear nucleus, defined as a large, optically clear nucleus, devoid of chromatin strands, with sharp chromatin rim, is a more specific feature than are nuclear grooves or intranuclear cytoplasmic inclusions in papillary thyroid carcinoma. In addition, this characteristic nuclear feature is detectable at low magnification. Although these clear nuclei are routinely seen in paraffin sections, they are inconspicuously seen in conventionally processed touch-imprints and fine-needle aspiration (FNA) smears. Among our two institutions, there have been 148 thyroid cases processed by Ultrafast Papanicolaou stain (UFP), including 43 papillary carcinomas, 38 cellular follicular lesions, and 67 cases of nodular hyperplasia. We observed clear nuclei in all of the cases of UFP-processed FNA and intraoperative smears of papillary carcinoma but not of other thyroid lesions. The clear nuclei are most evident in tumor cells with direct contact to the glass slide and are not seen in tumor cells soaked in cystic fluid. UFP is a valuable way to detect Orphan Annie-eyed clear nuclei of papillary thyroid carcinoma early in the diagnostic evaluation, either at immediate on-site evaluation of FNA or at intraoperative consultation and before the availability of permanent sections.
We report a case of an extremely rare neoplasm, malignant granular cell tumor (MGCT). The tumor occurred in the infratemporal fossa of a 30-year-old man, extended to the left orbital base, into the foramen ovale, and invaded the mandible. A granular cell tumor (GCT) was diagnosed by fine-needle aspiration and core needle biopsy of the mass. The patient underwent a radical subtotal debulking procedure followed by radiotherapy. He is alive with recurrent disease 12 months after presentation. Cytologically, the aspirated material was abundantly cellular showing large polygonal cells with ample granular eosinophilic cytoplasm, eccentric nuclei, and often prominent nucleoli. Histologically, the tumor consisted of solid sheets of similar cells that stained strongly with S-100 protein, neuron-specific enolase (NSE), and vimentin. There was moderate nuclear pleomorphism and broad zones of necrosis. Four mitotic figures per 100 high-power field (HPF) were counted. By electron microscopy, the cytoplasm of the tumor cells was filled with lysosomes. Although, some observers advocate that the diagnosis of a MGCT should be reserved for cases in which lymph node and/or distant organ metastasis is evident, we believe malignancy ought to be considered in any GCT with aggressive clinical course defined by persistent local recurrence and destruction of neighboring structures. Nuclear pleomorphism, necrosis, and presence of any mitotic activity should indicate malignancy.
Small studies have examined, with conflicting results, whether breast cancer risk is increased among women exposed to high levels of chlorinated hydrocarbons, as measured in breast fat tissue or peripheral blood collected prior to treatment (pretreatment blood). For a population-based, case-control study, collection of pretreatment blood is a labor-intensive effort. An alternative is to collect blood from cases at interview, as is done for controls, after breast cancer treatment has commenced (posttreatment blood). It is unknown whether treatment affects blood levels of the organochlorines 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) or polychlorinated biphenyls (PCBs). The purpose of this study was to determine whether pretreatment versus posttreatment blood samples yielded significantly different estimates of cumulative exposure to DDE and PCBs among newly diagnosed breast cancer patients. Two-ml blood samples were collected prior to and after treatment for breast cancer from 22 nonfasting women, ages 45-87 years, newly diagnosed with invasive disease. Treatment was defined as major surgery (mastectomy or node removal), radiation, hormones (tamoxifen), or chemotherapy. Pretreatment and posttreatment blood samples were assayed for DDE and PCBs in blinded, matched pairs. The reported concentrations (volume basis) were adjusted for estimated total plasma lipids. For DDE, mean differences in unadjusted [0.99 ng/ml; 95% confidence interval (CI), -0.36 to 2.34 ng/ml] and lipid-adjusted (0.05 microgram/g lipid; 95% CI, -0.04 to 0.13 microgram/g lipid) levels were small. For PCBs, the unadjusted (0.68 ng/ml; 95% CI, 0.05 to 1.30 ng/ml) and adjusted (0.070 microgram/g lipid; 95% CI, -0.009 to 0.149 microgram/g lipid) mean differences were of borderline statistical significance. The mean percent change in lipid-adjusted organochlorine levels did not vary substantially between treatment groups, except for those patients receiving chemotherapy [n = 5; 15.8% (DDE), 29.4% (PCBs)]. Adjusted mean differences also increased with increasing time between the pretreatment and posttreatment blood draws. In multiple regression models that included treatment, age, race, stage, and time between blood draws, only chemotherapy appeared to predict the percent change in adjusted pretreatment and posttreatment levels of DDE or PCBs (P = 0.10 and 0.06, respectively). Posttreatment blood samples drawn within 3 months of pretreatment samples, with the exception of those drawn after the commencement of chemotherapy, provide similar measures of DDE body burden levels among breast cancer cases. The use of blood samples collected after treatment, rather than before treatment, for characterizing PCB levels may lead to misclassification of exposure.
Carbon-laden macrophages in bronchoalveolar lavage have been noted to be associated with a history of crack smoking. We report herein the finding of carbon-laden macrophages in four cytological preparations of pleural fluid from two crack smokers. The etiology of the two patients' pleural effusions differed; neither had a bronchopleural fistula. Patient 1 had AIDS, Pneumocystis carinii pneumonia, and Kaposi's sarcoma of the right lung with an associated bilateral pleural effusion. Patient 2 was HIV seropositive, had pulmonary tuberculosis, hepatitis A, B, and C, cardiomyopathy, pulmonary embolism, and bilateral pleural effusions, the latter of which were probably due to cardio-pulmonary dysfunction. An additional two crack smokers with pleural effusions due to malignancy, one primary pulmonary adenocarcinoma and the other metastatic melanoma, did not have carbon-like material in their pleural fluid cytology. We hypothesize that intracellular accumulation of carbonaceous material in the lung parenchyma and pleural space occurs when normal clearance mechanisms are overwhelmed.
PURPOSE: To heighten awareness of colonic tuberculosis (TB) as a once rare disease that is undergoing a resurgence in the United States. METHODS: Report of a case of isolated sigmoid tuberculosis with a brief literature review of the topic. RESULTS: TB can no longer be considered a rare disease in the United States because, in part, of the acquired immunodeficiency syndrome epidemic and because, in part, of increased immigration and lack of containment. The signs and symptoms of colonic TB are nonspecific; therefore, a high index of suspicion must be maintained. Only 20 percent of patients will have associated active pulmonary TB. Colonoscopy with multiple biopsies at ulcer margins should be performed for diagnosis. Tissue should be sent for routine histology and culture and smeared for direct visualization of acid-fast bacilli. If colonic TB is suspected, empiric treatment is warranted, despite negative histology, smear, and culture results. Patients will usually show a dramatic response in one to two weeks. Treatment is solely medical, and all patients should receive a full course of antituberculous chemotherapy. Exploratory laparotomy is necessary if diagnosis is in doubt, when there is concern about a neoplasm, or for complications including perforation, obstruction, hemorrhage, or fistulization. CONCLUSION: An increased awareness of intestinal TB coupled with familiarity of the pathophysiology, diagnostic methods, and treatment should increase the number of cases correctly diagnosed preoperatively and, therefore, improve the outcome of patients with this disease.
A transvaginal sonographic (TVS) scoring system using morphologic features has been developed at our institution to maximize discrimination between benign and malignant ovarian and adnexal cysts. Low (4-7) or intermediate (8-9) scores have been found to correlate with benignity, hence TVS-guided or laparoscopically directed needle aspiration of low-scoring lesions may safely be performed. High-scoring lesions (10-14) are often malignant, therefore in situ needle aspiration of such lesions is not recommended. The aim of our study was to correlate the results of TVS characterization of ovarian and adnexal cysts with the aspiration cytologic evaluation. Twenty-three of the 43 cysts studied were aspirated in situ from the patient; 20 were aspirated from resected surgical specimens. Thirty-six benign cysts had TVS scores ranging from 4 to 12, with a median score of 7. All 25 cysts that were benign by TVS and/or histology were also cytologically benign as well as an additional 11 cysts that were not resected (TVS scores: 4 to 9). Seven cytologically and histologically malignant cysts had high TVS scores (TVS scores 10-14; median = 12). The combination of TVS and needle aspiration cytology is valuable, particularly in the diagnosis of cysts having low or intermediate TVS scores and benign cytology. Aspiration of cysts or masses with high TVS scores is not recommended. This combined evaluation may allow a more limited surgical approach, such as operative laparoscopy, or, in some cases, obviate the need for operative treatment altogether.
PURPOSE: To report on a vitreous specimen in a 53-year-old patient with unilateral choroiditis and vitritis of unknown cause. METHODS: Cytologic examination of a vitreous aspirate stained by the Papanicolaou method. RESULTS: Intravitreal spirochetes consistent with Borrelia burgdorferi were found in this seronegative patient. CONCLUSION: Vitreous specimens of patients with choroiditis and vitritis of unknown cause should be examined cytologically, particularly when serologic results do not corroborate the clinical findings of Lyme disease.
An athletic patient presented with a nontraumatic peroneal neuropathy that failed to resolve after a period of rest. A magnetic resonance image (MRI) showed a multilobulated mass in the course of the common peroneal nerve consistent with a plexiform neurofibroma. Surgical exploration revealed a mass, which coursed from the midthigh to the fibular neck, that was intimately involved with the fibers of the nerve bundle and had cystic degeneration with vesicles along its length. The authors recommend MRI as highly accurate in diagnosing unusual causes of peroneal neuropathy.
A retrospective study was performed on heavily pigmented pulmonary cytologic specimens from 14 hospital patients to determine the clinical features distinguishing these cases. The lavage fluid or sputum in each case was turbid and gray or black, exceeding the blackness usually seen in heavy tobacco smokers dwelling in the same urban environment. Excessive carbonaceous material was observed in the cytoplasm of pulmonary alveolar macrophages or the extracellular compartment of the smears. The latter feature is not seen in cigarette smokers. Many other pigmentary sources were ruled out, including melanin, hemosiderin, medicinal charcoal, India ink, and hematoxylin crystals. The common feature of the patients was that they recently or currently smoked the crack form of cocaine heavily; five patients also had positive toxicologic results for cocaine at admission. The authors suggest that blackened bronchoalveolar lavage fluid indicates the possibility of crack cocaine smoking and the associated sequelae, particularly when the carbonaceous material is present in the extracellular compartment.