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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.

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.

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.

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.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.Recombinant factor VIIa is an effective adjunct in the treatment of preeclamptic patients with expanding or ruptured subcapsular liver hematoma.

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.

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. Am. J. Hematol. 73:48–53, 2003. © 2003 Wiley-Liss, Inc.

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 β2-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.

Context.—The molecular genetic events involved in the pathogenesis of mature B-cell leukemias with more than 55% prolymphocytes are not well characterized. We have encountered 2 such cases in which conventional cytogenetic analysis identified Burkitt lymphoma–type chromosomal translocations involving 8q24. Objective.—To assess these 2 cases for involvement of the c-myc gene using fluorescence in situ hybridization analysis with probes specific for the c-myc and immunoglobulin heavy-chain (IgH) genes. Results.—In both cases, conventional cytogenetic analysis demonstrated complex karyotypes, including chromosomal translocations involving 8q24. In case 1, a case of de novo prolymphocytic leukemia, the t(8;14)(q24;q32) was detected. In case 2, a case of chronic lymphocytic leukemia in prolymphocytoid transformation, the t(8;22)(q24;q11) was identified. Fluorescence in situ hybridization studies showed c-myc/IgH fusion signals in case 1, proving the presence of the t(8;14). Split c-myc signals without fusion to IgH were observed in case 2, proving c-myc gene rearrangement and consistent with the t(8;22). Conclusion.—These results suggest that c-myc gene alterations may be involved in the pathogenesis of a subset of mature B-cell leukemias with more than 55% prolymphocytes.

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.

The myelodysplastic syndromes (MDS) are clonal hematologic malignancies characterized by pancytopenia, dysplastic hematopoiesis, and a propensity to leukemic transformation. Increased apoptosis has been noted in MDS as a possible explanation for ineffective hematopoiesis, with lower levels in progression to and in de novo acute leukemia. Apoptosis can be measured by binding of Annexin V to exposed membrane phosphatidylserine. We postulated that the apoptotic index would aid in the differential diagnosis of MDS versus other hematopoietic diseases. We examined 33 bone marrow aspirates suspected of hematopoietic malignancy for apoptotic index by Annexin V analysis using a Becton Dickinson FACStar+ flow cytometer. The apoptotic index was expressed as the percentage of Annexin V-positive cells divided by total mononuclear cells in the gate. By standard morphologic analysis, 16 cases were diagnosed as MDS (9 refractory anemia [RA], 2 refractory anemia with ringed sideroblasts [RARS], 1 refractory anemia with excess of blasts [RAEB], 3 chronic myelomonocytic leukemia [CMML], and 1 unclassified), 11 as acute leukemia (AL), 6 as myeloproliferative disorders (MPD). Eight cases (uninvolved marrow of five patients with lymphoproliferative disorders [LPD], one patient with multiple myeloma, and two patients with anemia of chronic disease) served as nonneoplastic controls. A higher degree of apoptosis was observed in MDS (mean = 44.7%; range = 29.5--60%) compared with MPD (mean = 8.2%; range = 2.3--15.4%), AL (mean = 16.1%; range = 5.1--29.4%), and control marrow samples (mean = 11.6%; range = 1.5--21%). Additionally, the apoptotic index was significantly higher in MDS compared with MPD (P < 0.0001). In conclusion, a high apoptotic index occurs in MDS, supporting previous reports and suggesting that Annexin V analysis can be used as an adjunct in the diagnosis of MDS versus MPD. This would be particularly useful for the often-difficult distinction between early MDS and early MPD cases with equivocal morphology.

Management of nonneoplastic thyroid nodules (TN) diagnosed by fine-needle aspiration (FNA) is controversial. While clinical follow-up with repeat FNA for enlarging TN is recommended in some studies, others recommend repeat FNA in follow-up of all benign TN after several months or years, in order to identify possible misdiagnosed malignant lesions. This study was done to determine the usefulness of repeat FNA in patients with benign nodular thyroid disease. We studied 94 fine-needle reaspirations performed on 43 females and 2 males 48.2 +/- 17 years of age with benign nodular thyroid nodular disease. Four patients had 3 consecutive FNAs and 41 patients had 2 consecutive FNAs. All FNAs were carried out by the same endocrinologist in the same thyroid area or by cytopathologists. The average time elapsed between the two consecutive FNAs was 18.3 +/- 11.2 (range, 4-48) months. Of the 45 patients, 23 presented with increase in size of the nodule and the remaining 22 patients did not have any change in size at the time of repeat FNA. Identical cytologic diagnoses were rendered in 39 of the 45 patients who underwent 2 or 3 consecutive FNA. Repeat FNA did not result in detection of any malignant neoplasms. Thyroid resection in 7 patients with increased nodule size and pressure symptoms confirmed the cytologic impressions of benign thyroid nodular disease. Our results show that the routine performance of repeated FNA cytology in the follow-up of patients with benign nodular thyroid disease with or without any clinical changes is of limited usefulness. Clinical factors rather than repeat FNA may hold precedence in surgical management of patients with benign nodular thyroid disease.

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.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.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.

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 5.4mm), 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.

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.

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.

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.

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.

We have encountered a peculiar vascular architecture in the myometrium wherein arteries are found free-floating within cleft-like spaces. Using different colored dye injections in the uterine arteries and veins, we demonstrated that these spaces are venous channels. This was confirmed by immunoperoxidase staining for CD34, which enhanced the cells lining these spaces. A review of 81 hysterectomy specimens showed that this vascular architecture was present in 42 cases (52%), while it was identified in the parenchyma of only two mastectomy specimens among the 45 specimens from different organs studied. A strong association existed between the presence of this architecture and history of menorrhagia (p = 0.0116). This peculiar vascular architecture might be important in the pathogenesis of menorrhagia and the development of intravenous leiomyomatosis. Pathologists should also be able to recognize these spaces as vascular channels in the event that malignant cells are identified within them.

Signet-ring cell carcinoma (SRCC) of lung is a rare variant of pulmonary adenocarcinoma. In view of this rarity, the question of whether an SRCC is primary pulmonary or metastatic arises frequently because the majority of SRCCs seen in lung are metastatic tumors having arisen in stomach, colon, or breast. On routine histologic examination it is difficult to distinguish between pulmonary SRCC from SRCC metastasizing from other organs. Thyroid transcription factor-1 (TTF-1) is a homeodomain-containing transcription factor that is almost exclusively expressed in thyroid and pulmonary epithelial cells. TTF-1 expression has been demonstrated in various neoplasms of lung; however, the expression of TTF-1 in SRCCs has not been investigated so far. In the present study, using an immunoperoxidase staining procedure on paraffin sections, we investigated the expression of TTF-1, cytokeratin 7, cytokeratin 20, and villin (a specific marker expressed in tumors of the digestive tract, renal proximal tubules, and hepatic bile ducts) in 32 SRCCs from various organs (17 lung, 5 breast, 5 stomach, and 5 colon). Fourteen (82.4%) of 17 pulmonary SRCCs exhibited TTF-1 positivity, whereas none of the SRCCs of other organs were positive for TTF-1. A cytokeratin profile (CK7+/CK20-) was identified in 94.1% of pulmonary SRCC, and although it differed from the profile exhibited in colonic SRCCs (CK7-/CK20+), a similar profile was seen in breast SRCCs and some SRCCs arising in the stomach. Villin was identified in 29.4% of pulmonary SRCCs and 20% (one case) arising in the breast. Although the pattern of villin immunostaining exhibited by nondigestive tract SRCCs (cytoplasmic) differed from those of digestive tract SRCCs (membranous), distinguishing between the two groups based on their pattern of immunostaining alone would be difficult. The results of this study indicate that TTF-1 is expressed in a high percentage of pulmonary SRCCs and is very specific and that TTF-1 would be extremely valuable in distinguishing pulmonary SRCCs from those arising in other organs.

Background: Spillage of bile or gallstones, a relatively common occurrence during laparoscopic cholecystectomy, is believed to be inconsequential, but we describe a case of postlaparoscopic granulomatous peritonitis mimicking endometriosis. Case: A 20-year-old gravida 0 presented with chronic lower abdominal pain and dysmenorrhea. Laparoscopy showed red-brown pigmented pelvic adhesions, which on biopsy showed foreign-body–type granulomatous reaction, both suggesting endometriosis, but a history of laparoscopic cholecystectomy and a positive Fouchet’s stain for bile gave the true etiology of the granulomatous reaction. Conclusion: With increasingly widespread use of laparoscopic cholecystectomy, and relatively common spillage of bile or gallstones at surgery, granulomatous peritonitis mimicking endometriosis might become more frequent.