Low grade fibromyxoid sarcoma: report of a case with epithelioid cell morphology, masquerading as a papillary thyroid carcinoma.

BACKGROUND: Low grade fibromyxoid sarcoma (LGFMS) is a rare tumor with a characteristic histologic appearance. Although the spectrum of histologic features that can be seen in LGFMS a well characterized, their description in the cytology literature is lacking. CASE: A 57-year-old male with a past history of Hodgkin's lymphoma presented with 1-year history of dysphagia. Clinical examination and radiologic imaging studies revealed a neck mass suggestive of a thyroid lesion. Fine needle aspiration cytology of the mass revealed moderately cellular smears with several cohesive clusters. Most of the clusters showed cellular crowding with overlapping nuclei. The nuclei ranged from round to oval or elongated shapes with frequent irregular nuclear membranes, powdery to clear nuclear chromatin and inconspicuous nucleoli. Most notably, several intranuclear inclusions and nuclear grooves were noted, leading to a suggestion of a papillary thyroid carcinoma. Histopathologic examination of the mass revealed an LGFMS. CONCLUSION: This report describes a rare case of LGFMS with epithelioid morphology. By virtue of its clinical presentation and cytologic features, the case masqueraded as a papillary thyroid carcinoma and should be added to the list of pitfalls in the diagnosis of papillary thyroid carcinoma. The case also serves to add to the spectrum of morphologic changes that can be seen in LGFMS.

Sporadic duodenal bulb gastrin-cell tumors: association with Helicobacter pylori gastritis and long-term use of proton pump inhibitors.

We reviewed the clinicopathologic profile of a series of recently diagnosed sporadic duodenal gastrin-cell (G-cell) tumors. All cases were discovered incidentally and had a unique clinicopathologic profile: all 18 cases were gastrin-positive tumors located in the duodenal bulb, were small in size (mean size 5.4 mm), demonstrated an insular architectural pattern, and were localized to the lamina propria and submucosa. None of the patients had Zollinger-Ellison or carcinoid syndrome. The behavior was indolent and there was no evidence of metastasis at diagnosis or during follow-up. In our sampled population, the presence of Helicobacter pylori gastritis and the use of proton pump inhibitors (PPIs) were significantly associated with the presence of G-cell tumors. Both the presence of H. pylori gastritis and use of PPI remained significant in a logistic regression model adjusted for age, race/ethnicity, and sex with P values of 0.0016 (odds ratio=10.1, 95% confidence interval: 2.3 to 42.4) and 0.008 (odds ratio=8.9, 95% confidence interval: 1.76 to 45.4), respectively. Most patients with tumors showed G-cell hyperplasia in the nontumorous regions of the duodenum. The high incidence of sporadic duodenal G-cell tumors in patients with H. pylori gastritis and long-term PPI use suggests an association that needs to be further explored. Presence of G-cell hyperplasia in the nontumorous duodenal mucosa suggests that these may originate from a proliferative phase, similar to the hyperplasia-dysplasia-neoplasia sequence seen in other endocrine tumors.

Morphologic and immunophenotypic analysis of angioimmunoblastic T-cell lymphoma: Emphasis on phenotypic aberrancies for early diagnosis.

The morphologic features and immunophenotype of diagnostic nodal and bone marrow biopsy specimens were reviewed in 29 well-established cases of angioimmunoblastic T-cell lymphoma (AILT). All cases showed a characteristic polymorphous lymphoid and inflammatory cell infiltrate along with stromal-vascular changes. Perivascular aggregation or clustering of neoplastic clear cells was seen in only 41% of cases. Unique architectural changes, including extranodal extension (83%), follicular dendritic cell proliferation (93%), and a distinctly marginalized distribution of residual B cells (67%) were observed. Subsets of T cells with immunophenotypic abnormalities (CD10 coexpression or loss of pan-T-cell antigens CD3 and CD7) were identified in a majority of cases (96%). Significantly, these morphologic and phenotypic features were seen irrespective of the presence of an overt lymphomatous pattern. Bone marrow involvement was present in 90% of patients with available biopsy specimens. Our results indicate that unique morphologic alterations and subsets of phenotypically aberrant T cells are present consistently in nearly all cases of AILT, including morphologically less definitive biopsy specimens.

p57KIP2 immunohistochemistry in early molar pregnancies: emphasis on its complementary role in the differential diagnosis of hydropic abortuses.

Morphologic examination still forms the main diagnostic tool in the differential diagnosis of molar pregnancies. However, the criteria are subjective and show considerable interobserver variability among pathologists. Once a diagnosis of molar pregnancy is made, DNA ploidy studies help to differentiate a triploid partial mole from diploid complete mole (CM). However, with earlier diagnosis and therapeutic evacuation of molar pregnancies, the differentiation of molar pregnancies from early nonmolar placentation is becoming increasingly difficult. The p57(KIP2) gene ( CDKN1C ) is strongly paternally imprinted and expressed from the maternal allele. Because CM lacks a maternal genome, p57(KIP2) immunostaining is correspondingly absent, whereas hydropic abortuses and partial mole show positive staining. We compared the use of p57(KIP2) staining in the differential diagnosis of 68 morphologically challenging cases of early first-trimester hydropic placentas. Diagnosis based on p57(KIP2) staining was compared with the original diagnosis based on morphology and DNA ploidy analysis. Concordant results were obtained in 65 of 68 cases studied. In 2 of 3 cases with a discordant diagnosis, microsatellite DNA genotyping analysis agreed with the results of p57(KIP2) staining, confirming that positive p57(KIP2) staining is a highly sensitive and specific marker for excluding CM in this setting. In addition, p57(KIP2) staining has the advantage of differentiating hydropic abortuses from CMs, a distinction not made by ploidy analysis. p57(KIP2) staining can be used in concert with ploidy studies to refine the diagnosis of early molar pregnancies.

Fluorescence in situ hybridization identifies cryptic t(16;16)(p13;q22) masked by del(16)(q22) in a case of AML-M4 Eo.

We report a patient presenting with acute myeloid leukemia (AML)-M4 Eo, in whom conventional cytogenetic analysis revealed a 46, XY, del(16)(q22) karyotype. Molecular analysis of the bone marrow cells using reverse transcriptase polymerase chain reaction (RT-PCR) identified a CBFbeta-MYH11, "type A" fusion transcript. However, despite a thorough reevaluation, a balanced chromosome 16 abnormality could not be definitively identified by cytogenetics. Since there exists a small possibility of obtaining a false-positive PCR result, fluorescence in situ hybridization (FISH) analysis using dual-color, break-apart probes for CBFbeta was performed to elucidate the mechanism of fusion gene formation and thus confirm the RT-PCR results. FISH analysis clearly revealed a cryptic t(16;16), which was probably masked by the del(16)(q22). FISH is the preferred diagnostic procedure to elucidate the CBFbeta-MYH11 fusion in this situation, and resolves the possibility of both false-positive and false-negative results with RT-PCR technique. Due to the improved prognosis of AML associated with the CBFbeta-MYH11 fusion compared to AML generally, we recommend the use of FISH for detection of inv(16)/t(16;16)/CBFbeta-MYH11 in patients with failed, complex, or apparently normal cytogenetics, and in whom the cell morphology indicates the strong possibility of this gene fusion.

Micropapillary component in lung adenocarcinoma: a distinctive histologic feature with possible prognostic significance.

Micropapillary carcinoma or a micropapillary carcinoma component has been reported in the ovary, breast, and urinary bladder and is generally thought to have prognostic significance. However, little has been written on micropapillary differentiation in lung carcinoma. We studied 35 cases of primary lung adenocarcinoma with a micropapillary component seen at the M.D. Anderson Cancer Center. The micropapillary component in these tumors ranged from focal to prominent and was seen at both primary and metastatic sites. This component was not associated with any particular histologic subtype of lung adenocarcinoma. Of the 15 cases with available material, 14 (93%) stained positive for cytokeratin 7, whereas only two of the 15 cases (13%) stained positive for cytokeratin 20. Thyroid transcription factor-1 immunostaining of tumor nuclei was seen in 12 of the 15 cases (80%). Immunostaining was seen in areas both with and without micropapillary differentiation. Thirty-three of 35 patients (94%) developed metastases, which occurred most commonly in the lymph nodes (n = 26), and also in the lung (n = 17), brain (n = 9 cases), bone (n = 9 cases), and other sites. Most metastases had a prominent micropapillary component, irrespective of the extent of the micropapillary carcinoma component in the primary lung tumor. Adequate clinical follow-up information was available for 29 patients. The mean follow-up was 25 months. At their last follow-up, 16 of 29 patients (55%) were still alive with disease, 5 (17%) were dead of disease, and 8 (28%) were alive with no evidence of disease. We believe that a micropapillary component occurring in lung adenocarcinoma should be reported, as this component may be more likely to metastasize. The presence of this component should alert the clinician to search more carefully for metastases and have a closer follow-up on these patients. It is also important to recognize this component in evaluating a metastasis from an unknown primary site, as it should alert the pathologist to a possible primary in the lung in addition to breast, urinary bladder, and ovary.

Epstein-Barr virus-associated intravascular large T-cell lymphoma presenting as acute renal failure in a patient with acquired immune deficiency syndrome.

Intravascular lymphoma (IVL) is a rare neoplasm, recently included as a specific entity in the World Health Organization classification of lymphoid tumors. Most cases are of B-cell lineage; however, rare cases of T-cell phenotype have been reported. We report a human immunodeficiency virus (HIV)-positive patient who died of acute renal failure in whom IVL was identified at autopsy, predominantly involving the renal interstitial vessels. Immunohistochemical stains revealed a T-cell phenotype, which was confirmed by T-cell receptor gamma gene rearrangement studies. The lymphoma cells showed nuclear Epstein-Barr virus (EBV)-encoded RNA transcripts by in situ hybridization, suggesting that EBV might be of etiologic importance in this tumor. The predominant involvement of kidney is unusual. With effective therapy, morbidity and mortality of HIV-1 infection has been substantially reduced, and survival times have been prolonged. However, the relative risk of secondary neoplasms, especially non-Hodgkin's lymphoma (NHL), has increased. Consequently, we conclude that unique types of NHL, such as this case of IVL, may be encountered more frequently in this patient population, and that NHL should be added to the list of differential diagnostic considerations in HIV-1-positive patients who develop acute renal failure.

Recombinant factor VIIa in management of spontaneous subcapsular liver hematoma associated with pregnancy.

BACKGROUND: Spontaneous subcapsular liver hemorrhage is a rare but life-threatening complication of pregnancy. Optimal management of an expanding hematoma or ruptured capsule has not been established. CASES: We report 3 patients with preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome with spontaneous subcapsular liver hematomas. The first 2 patients with ruptured liver hematomas experienced life-threatening hemorrhage. The third patient experienced uncontrollable vaginal bleeding, liver hemorrhage, and was in imminent danger of capsule rupture. Despite aggressive surgical intervention and traditional blood component therapy, adequate hemostasis could not be achieved in any of these patients. Recombinant factor VIIa was used to achieve hemostasis in all three patients. CONCLUSION: Recombinant factor VIIa is an effective adjunct in the treatment of preeclamptic patients with expanding or ruptured subcapsular liver hematoma.

Myelolipoma associated with adrenal ganglioneuroma.

Adrenal myelolipomas are rare, benign mesenchymal tumors composed of mature adipose tissue and hematopoietic cells in varying proportions. Although the majority of cases occur as isolated adrenal lesions, myelolipomas have been described in association with various adrenal pathologic conditions. These conditions include enzyme deficiencies and hyperplastic and neoplastic lesions of the adrenal cortex, with perhaps endocrine dysfunction as a common feature. Ganglioneuroma is a benign tumor of the sympathetic nervous system that rarely produces symptoms of endocrine dysfunction. We report an unusual case of myelolipoma associated with ganglioneuroma of the adrenal medulla. The histogenesis of myelolipoma remains speculative. However, the close proximity to adrenal cortical cells within the stroma of ganglioneuroma suggests that the hormonal microenvironment may have played a role in the development of the myelolipoma.

Indium-111 pentetreotide uptake by pancreatic polypeptide cell hyperplasia: potential pitfall in somatostatin receptor scintigraphy.

A 71-year-old man with duodenal gastrin cell tumor was being evaluated for residual/metastatic disease. Somatostatin receptor scintigraphy (SRS) identified a 2-cm area of focal uptake within the head of the pancreas, consistent with a pancreatic neuroendocrine tumor. Pathological examination did not reveal any malignancy within the pancreas. Instead, the pancreatic head showed pancreatic polypeptide cell hyperplasia. Strong and diffuse immunoreactivity to somatostatin receptor 2A antibody by immunoperoxidase staining confirmed that the lesion correlated with the site of radioactive tracer (Indium-111 pentetreotide) uptake seen on SRS. The current report therefore presents pancreatic polypeptide cell hyperplasia as a new pitfall in SRS.

Alleviation of systemic manifestations of multicentric Castleman's disease by thalidomide.

Multicentric Castleman's disease (MCD) is a rare lymphoproliferative disorder of unknown etiology. Although HHV-8 (human herpesvirus type 8) has been suggested as a possible etiologic agent in a subpopulation of cases, appropriate treatment of the HHV-8 infection has not produced regression of the disease. Additionally, other treatment modalities, including steroids and various regimens of chemotherapy, do not consistently provide good control of the disease. Clinical signs and symptoms of the disease are primarily mediated by cytokines, especially interleukin-6 (IL-6). We report a case of multicentric Castleman's disease that responded dramatically to single agent thalidomide. A powerful cytokine disruptor, thalidomide may have good therapeutic efficacy in treating MCD and related cytokine-mediated disorders.

Amelioration of ischemia-reperfusion injury with cyclic peptide blockade of ICAM-1.

Neutrophils are pivotal in the pathogenesis of ischemia-reperfusion (I/R) injury leading to muscle damage. Firm adhesion of neutrophils to the endothelium is initiated by an interaction between intercellular adhesion molecular-1 (ICAM-1) on the endothelium and beta(2)-integrins on neutrophils. Inhibition of ICAM-1-dependent binding using monoclonal antibodies has been shown to be efficacious in ameliorating I/R injury by preventing the influx of neutrophils into the ischemic tissue. We recently described a cyclic peptide that is a potent and selective inhibitor of ICAM-1 (IP25) in vitro. In this study, we tested the hypothesis that IP25-mediated blockade of ICAM-1 would inhibit neutrophil influx during reperfusion of ischemic tissue and consequently attenuate muscle injury in a tourniquet hindlimb murine model of I/R injury. Varying amounts of peptide drug were injected at the beginning of the reperfusion period. The neutrophil influx and size of infarction at the end of 2 h of reperfusion were compared with those in untreated control mice and contralateral nonischemic limbs. Mice receiving IP25 immediately before reperfusion showed a 56% reduction in neutrophil infiltration in the ischemic muscle, accompanied by a 40% reduction in the infarct size. No effect on I/R injury was seen if IP25 administration was delayed for 60 min after reperfusion. We conclude that IP25 effectively inhibits ICAM-1-mediated adhesion of neutrophils to the endothelium in mice leading to a protective effect and suggests that synthetic peptide antagonists have a potential role as therapeutic tools.