WT1 staining reliably differentiates desmoplastic small round cell tumor from Ewing sarcoma/primitive neuroectodermal tumor. An immunohistochemical and molecular diagnostic study.

Differentiating desmoplastic small round cell tumor (DSRCT) from another similar small round cell tumor of childhood, the Ewing sarcoma/primitive neuroectodermal tumor (EWS/PNET), can be difficult because morphologic and immunohistochemical features overlap. We studied the predictive value of immunohistochemistry with an antibody to the C-terminal region of the Wilms tumor (WT1) protein for differentiating DSRCT from EWS/PNET in 24 malignant small round cell tumors that had been previously diagnosed as DSRCT or EWS/PNET by standard methods. We performed reverse transcriptase-polymerase chain reaction (RT-PCR) analysis in cases with available tissue as a confirmatory measure: 6 of 13 DSRCTs were informative by RT-PCR, and 6 of 6 showed an EWS-WT1 fusion; all 13 DSRCTs showed strong, definitive nuclear staining with the WT1 antibody. All 11 EWS/PNETs were WT1 antibody negative; 7 of 11 cases classified as EWS/PNET were informative by RT-PCR, and 7 of 7 showed an EWS-FLI-1 fusion. For cases in which the morphologic and immunohistochemical features are consistent with a diagnosis of DSRCT, WT1 antibody staining predicts the EWS-WT1 translocation with high sensitivity and specificity and is, therefore, useful for differentiating DSRCT from EWS/PNET when genetic information is unavailable.

Molecular analysis of malignant triton tumors.

Triton tumors are rare variants of malignant peripheral nerve sheath tumor (MPNST) with muscle differentiation, often seen in patients with neurofibromatosis 1 (NF1). Individuals affected with NF1 harbor mutations in the NF1 tumor suppressor gene and develop neurofibromas and MPNSTs. The NF1 gene is expressed in Schwann cells and its expression is lost in schwannian neoplasms, suggesting a role in malignant development. Separately, there is evidence that p53 suppressor gene mutations are involved in MPNSTs. To determine the role of the NF1 and p53 genes in the development of the malignant Triton tumor we examined 2 such tumors, 1 from a 3-year-old boy without clinical manifestations of NF1 and another from a 24-year-old man with NF1. Histological analysis of these tumors showed both neural and muscle differentiation with S-100 and desmin immunoreactivity, respectively. Reverse transcribed RNA polymerase chain reaction (RT-PCR) of NF1 mRNA showed NF1 expression in the sporadic tumor. Strong nuclear immunoreactivity for p53 was observed throughout the malignant population in both tumors. This was confirmed by loss of heterozygosity for p53 in the non-NF1 patient, suggesting that p53 is involved in both hereditary and sporadic Triton tumors. The finding of preserved NF1 gene expression in the non-NF1-related Triton tumor suggests that different genetic events predispose to the development of this rare neoplasm in sporadic cases.

p53 and Ki-67 proliferating cell nuclear antigen in benign and malignant peripheral nerve sheath tumors in children.

Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon soft tissue tumors. In children with neurofibromatosis 1 (NF1), a MPNST often arises in a pre-existing neurofibroma, or may represent an initial manifestation without other obvious stigmata of the disease. The development of MPNSTs may be associated with instability of the p53 tumor suppressor gene since it is the most frequent genetic abnormality in soft tissue sarcomas. To assess the presence of p53 accumulation in MPNSTs and its correlation with clinical and pathologic features, we studied 12 neurofibromas (NFs), including 4 tumors with cellular features (one congenital) and 10 MPNSTs. Six MPNSTs were associated with NF1, all of which developed within a plexiform neurofibroma. Cell proliferation evaluated with an antibody to Ki-67 and nuclear p53 staining were both detected by immunohistochemistry. We found p53 positivity in 60% of MPNSTs. All NFs except the congenital tumor were p53 immunonegative (P < 0.01). Rare p53-positive nuclei were detected in the transitional zone in two of six MPNSTs arising in plexiform NFs. Ki-67 distinguished the NFs from MPNSTs (P < 0.005). Half of the NF1 patients with p53-positive MPNSTs developed recurrence or metastases or developed a second malignancy within 2 years of diagnosis, whereas patients with p53-positive sporadic MPNSTs were free of disease 1 to 7 years later. We found p53 accumulation more frequently in NF1-associated MPNSTs. p53 mutations may be an additional biologic factor to account for the poor prognosis in these tumors.

Deep granuloma annulare (pseudorheumatoid nodule) in children: clinicopathologic study of 35 cases.

Deep granuloma annulare (DGA) is one of several lesions of skin and superficial soft tissues whose histologic character is a palisading granuloma with a small central focus of necrosis or necrobiosis. Unlike the other palisading necrobiotic lesions, DGA has a predilection for children in the first 5 to 6 years of life. A painless subcutaneous nodule(s) in the lower anterior tibial region or foot and the scalp, typically in the occiput, was the most common presenting feature in this study of 35 cases. Additional or recurrent lesions were reported in approximately 70% of cases with clinical follow-up. All lesions showed the presence of necrobiosis; however, one of the characteristic features was the multinodular character of the predominantly mononuclear cellular aggregates. The presence of vascular spaces at the periphery of the nodular profiles served as a clue to the diagnosis of DGA. The palisading arrangement of the mononuclear cells was evident only in those foci with central necrobiosis. A histiocytic disorder or fibrohistiocytic process was a common consideration in the differential diagnosis, especially in those cases with less apparent foci of necrosis. Palisading histiocytes with prominent eosinophilic cytoplasm and some nuclear atypism were problematic with regard to possible epithelioid sarcoma. Our study failed to identify any underlying or predisposing factors in the development of DGA. Despite the fact that DGA is a well-documented lesion in children, it occurs sufficiently infrequently that it is often not considered clinically when it presents as a subcutaneous mass or masses in a child. Its recognition by the pathologist is especially important as the occurrence of additional lesions in a high proportion of children can be anticipated without undue concern.

Histopathologic analysis of interval appendectomy specimens: support for the role of interval appendectomy.

The treatment of appendiceal abscess is controversial. For patients initially treated "conservatively" with antibiotics with or without drainage, the role of interval appendectomy is an area of considerable debate. Without interval appendectomy, the true risks of recurrent disease and missed pathological findings are uncertain, and large, long-term, prospective studies are unavailable. To evaluate the role of interval appendectomy, the authors reviewed the histopathologic specimens from patients with presumed appendiceal abscess treated by interval appendectomy. Over a 7-year period, 162 children presented with a clinical diagnosis of perforated appendicitis. Eighteen patients had localized abscesses treated conservatively, followed by interval appendectomy. Standard histopathologic sections of 17 of the 18 appendices were examined by one pathologist who was blinded to the clinical data and to the interpretation of the original pathologist. Of the 11 boys and seven girls (mean age, 7.4 +/- 3.4 years), eight underwent percutaneous drainage and one underwent operative drainage. All received intravenous antibiotics for a mean of 8.6 +/- 3.2 days with a hospital stay of 10.4 +/- 8.3 days. Interval appendectomy was performed at a mean of 92.7 +/- 20.7 days after initial admission, with discharge at a mean of 2 +/- 1.3 days after surgery. There were no complications or deaths. Histopathologic review showed normal appendix (n = 4), normal appendix with mild serositis (n = 6), normal appendix with unsuspected resolved Meckel's diverticulitis (n = 1), appendiceal duplication (n = 1), granulomatous appendicitis (n = 3), and acute appendicitis (n = 2). All appendices had patent lumens, and 15 were documented to be present to the tip. There was no correlation between the histopathologic findings and the interval between abscess and interval appendectomy. Interval appendectomy was performed with no morbidity and a short hospital stay. Two patients had histopathologic recurrent acute appendicitis, five had unsuspected pathological findings (appendiceal duplication, Meckel's diverticulitis, granulomatous inflammation), and none of the appendices had an obliterated lumen, suggesting that all patients were at long-term risk for recurrent disease. These data support the role of interval appendectomy in cases of perforated appendicitis treated conservatively.

Papillary tissue fragments as a diagnostic pitfall in fine-needle aspirations of thyroid nodules.

Fine-needle aspirates of three thyroid nodules displayed hypercellularity and papillary tissue fragments that suggested neoplasms. Neither microfollicles (either empty or with inspissated colloid) nor the characteristic nuclei of papillary carcinoma were evident. Surgical specimens contained adenomatoid nodules with focal papillary hyperplasia. These cases demonstrate that no single cytologic feature should be used independently in the cytologic diagnosis of thyroid lesions. Tumor cellularity and papillary tissue fragments should not be equated with neoplasia per se; all cytomorphologic features should be evaluated.

Primitive neuroectodermal tumor of the kidney--another enigma: a pathologic, immunohistochemical, and molecular diagnostic study.

Primitive neuroectodermal tumor (PNET), the second most common type of sarcoma in the first two decades of life, rarely presents as an organ-based neoplasm. Rather, it is seen typically in the soft tissues of the chest wall and paraspinal region. We report a case of primary PNET of the kidney in a 17-year-old girl who presented with abdominal pain, hematuria, and an abdominal mass. Nodules and sheets of monotonous-appearing primitive round cells and the formation of rosettes focally were the principal microscopic features. The tumor cells were uniformly immunoreactive for vimentin, cytokeratin, neuron-specific enolase, and 013 (CD99). In addition, the characteristic translocation of PNET and Ewing sarcoma, t(11;22)(q24;q12), was detected by polymerase chain reaction (PCR). Eight previous examples of renal PNET have been reported in the literature in the past 2 years, but only three of these cases have had complete immunohistochemical evaluation with the demonstration of 013 positivity. To our knowledge the present case is the only one to date demonstrating the recurrent translocation t(11;22)(q24;q12) by PCR. Assuming that the previous cases in the literature are bona fide examples of PNET, the kidney may be another site of predilection for this usual soft-tissue neoplasm. We are once again confronted with the dilemma about the nature of the progenitor cell.

Fine-needle aspiration of thyroid lesions in 57 pregnant and postpartum women.

Palpable thyroid nodules are common in women. The thyroid gland may enlarge in response to hyperemia, relative iodine depletion, and slight stimulation by beta Human Chorionic Gonadotrophin (HCG) during pregnancy. The presence of goiter or a discrete nodule requires investigation. Fine-needle aspiration (FNA), a reliable diagnostic tool, can be safely used during pregnancy. The tenet that a "histologic hyperplasia" accompanies the physiologic hyperplasia of pregnancy may hamper FNA interpretation. We reviewed 97 (10 previous, 46 pregnant, 13 postpartum, 1 spontaneous abortion, and 27 follow-up) aspirates of thyroid nodules from 57 patients. Cytologic diagnoses were divided into five categories: 31 benign, 7 cellular adenomatoid nodules, 5 suspicious for papillary carcinoma, 12 papillary carcinomas, and 2 follicular neoplasms. There were an unanticipated number of carcinomas. Lesions present before pregnancy did not show "progression" or significant change. No characteristic features ascribable to pregnancy were identified. Standard diagnostic criteria may be used in the evaluation of FNA of thyroid nodules from pregnant patients.

Acute monocytic leukemia (FAB M5) involving the placenta associated with delivery of a healthy infant: case report and discussion.

Acute leukemia seldom presents during pregnancy, and though pregnancy may not affect the course of leukemia, fetal complications and maternal mortality are high. Documented placental involvement is rare, as are metastases to the fetus. Comprehensive review of the literature reveals only a few reports of maternal or fetal leukemia with placental involvement. We encountered a case of a 45-year-old woman who presented at 29 weeks' gestation with acute monocytic leukemia with t(9;11). She was managed conservatively. Labor was induced at 33 weeks, with delivery of a healthy male infant prior to induction chemotherapy. The baby remained well at 18 months of age. The placenta showed isolated microinfarcts and an infiltrate in the basal plate of leukemic cells confirmed by immunohistochemistry. No invasion into chorionic villi was seen. Little is known about the biological significance of placental involvement and inherent defense mechanisms of the placenta in maternal cancers. Therefore, detailed histopathologic examination of the placenta should always be performed and reported in leukemic patients, regardless of fetal outcome.

Myocardial extramedullary hematopoiesis following myocardial infarction.

Extramedullary hematopoiesis (EMH) usually accompanies a chronic hematologic disease in adults or prematurity in neonates. We observed a striking case of EMH in the explanted heart of a 13-year-old boy who underwent transplantation after extensive myocardial infarction. The florid myeloid proliferation raised the possibility of a leukemic process. To our knowledge, extensive myocardial EMH subsequent to myocardial infarction has not been previously reported. Possible mechanisms underlying EMH in the myocardium are presented.

Evaluation of E-Test for determination of antimicrobial MICs for Pseudomonas aeruginosa isolates from cystic fibrosis patients.

We determined the E-Test and National Committee for Clinical Laboratory Standards standardized agar dilution MICs of ceftazidime, ciprofloxacin, piperacillin, and tobramycin for Pseudomonas aeruginosa during tests of 100 rough and mucoid P. aeruginosa isolates from cystic fibrosis patients. The levels of agreement (+/- 1 log2 dilution) between quantitative E-Test and agar dilution MIC results were 80, 97, 73, and 89% for ceftazidime, ciprofloxacin, piperacillin, and tobramycin, respectively. Comparison of the results after converting the MIC data to qualitative categories (susceptible, intermediate, and resistant) yielded levels of agreement of 84, 96, 88, and 93% for the same agents, respectively. Of the 39 qualitative discrepancies, 36 were minor and 3 were very major. We conclude that use of the E-Test is easier and more practical than use of the agar dilution method for most laboratories and that the E-Test furnishes results which are at least as accurate as those obtained by the agar dilution method. However, the higher cost of the E-Test method would likely discourage most laboratories from selecting it over disk diffusion for routine antimicrobial susceptibility testing of P. aeruginosa isolates from cystic fibrosis patients.

Fatal Bacillus cereus meningoencephalitis in an adult with acute myelogenous leukemia.

Bacillus cereus, a ubiquitous, endospore-forming, aerobic gram-positive bacillus, is primarily associated with toxin-mediated food poisoning. Frequently, isolates of Bacillus species from clinical specimens are discussed as contaminants. We report a rapidly fatal case of disseminated infection due to B cereus in a patient receiving induction chemotherapy for M0 acute leukemia. A short clinical syndrome of nausea and vomiting preceded neurologic symptoms. Autopsy showed extensive meningoencephalitis with subarachnoid hemorrhage and multiple liver abscesses. Areas of necrosis were devoid of any inflammatory response consistent with a severely immunocompromised state. The organism was isolated from immediate premortem and autopsy blood specimens. This case illustrates the possibility and severity of true B cereus infections in immunocompromised patients, the clinicopathologic features of which are as yet not well defined.