Familial Wilms' tumor with neural elements: characterization by histology, immunohistochemistry, and genetic analysis.

Wilms' tumor (WT) is the most common renal malignancy of children. While most occur sporadically, a small percentage are familial or occur as part of a developmental syndrome. Classic WTs exhibit a triphasic histologic pattern composed of blastema, epithelium, and stroma. Occasionally, heterologous elements may also be observed. In this study we investigated a series of four WTs that occurred within a single familial aggregate and contained focal areas of neural differentiation. The tumors were evaluated histologically for the presence of neural elements and immunohistochemically for expression of neural-related markers. Genetic linkage analysis was performed on 3 of the 4 WTs. In addition to the classic triphasic histology, the WTs contained tumor rosettes (4/4), ganglion cells (2/4), foci of ganglioneuromatous differentiation (2/4), and anaplasia (1/4). Staining for chromogranin, S-100, synaptophysin, vimentin, and neuron-specific enolase was positive in all 4 tumors within the areas of neural differentiation whereas staining for CD99 (013) and glial fibrillary acidic protein was negative. Linkage analysis studies suggest that the familial predisposition gene segregating in this family is at 19q13.4. To our knowledge, this is the first reported series of WTs with neural differentiation that occurred within a single family aggregate. Genetic linkage analysis of this family is consistent with linkage to the FWT2 WT predisposition gene at 19q13.4. We propose that these tumors may represent a unique manifestation of tumor susceptibility in this family.

Diagnosis and classification of lymphoma based on cytospin preparations: a comparison of hematopathologists and cytopathologists.

The diagnosis of malignant lymphoma based on cytologic preparations is a source of much debate. The purpose of this study was to assess the ability of a number of pathologists to diagnose and classify lymphoma using cytospin preparations, and to compare the rate of agreement between cytopathologists and hematopathologists. One hundred twenty-five cytospins prepared from histologically confirmed hematologic lesions were examined retrospectively and independently by four hematopathologists/fellows and two cytopathologists without knowledge of the final diagnosis; the results were compared with the final diagnoses derived from histology and immunophenotyping. Eighty-one cases were histologically diagnosed as lymphoma (including 67 cases of B-cell non-Hodgkin's lymphoma), and 44 cases represented a reactive process histologically. The distinction of a malignant from a benign process was made in 75% of the cases by cytospin examination, with cytopathologists correctly diagnosing 75% and hematopathologists 76% of the cases. The accuracy rate for subclassification of the lymphoma cases was 49% (46% for cytopathologists, 52% for hematopathologists). The cytopathologists correctly recognized large-cell lymphoma at an increased frequency compared with the hematopathologists (70% vs. 56%, P = 0.11), while the hematopathologists showed a greater ability to recognize and classify nonfollicle center low-grade B-cell lymphomas (57% vs. 28%, P = 0.01). We conclude that cytopathologists and hematopathologists generally achieve similar accuracy rates in the morphologic evaluation of cytologic preparations of lymphoid lesions, though some differences in their performance do exist.

Evidence of increased angiogenesis in patients with acute myeloid leukemia.

Angiogenesis plays a key role in solid tumor growth. The purpose of this work was to study angiogenesis in acute myeloid leukemia (AML). We stained bone marrow samples from 20 adult patients with untreated AML and 20 normal controls using endothelial cell markers (ULEX-E and von Willebrand factor [vWF]). The number of vessels per millimeter length of bone marrow core biopsy specimen was scored by light microscopy. Using ULEX-E staining, AML marrows had (average +/- SEM) 8.3 +/- 3.6 vessels/mm (range, 3.7-19.3), whereas normal marrows had 4.3 +/- 1.8 vessels/mm (range, 1.6-7.9). A similar difference was noted using vWF staining (8.6 +/- 3.0 vessels/mm vs 4. 9 +/- 2.2 vessels/mm in AML vs normal bone marrows, respectively). The differences between the numbers of vessels/mm in AML and normal marrows were highly significant (P <.0001 for both ULEX-E and vWF staining). When analyzed by FAB category, there was no difference in the average number of vessels/mm among the different subgroups of AML. Using reverse transcriptase polymerase chain reaction, we observed that the HL-60 and U937 human AML cell lines and 4 of 4 freshly isolated AML cells from untreated patients expressed mRNA for vascular endothelial growth factor (VEGF). Both cell lines as well as all fresh AML isolates tested expressed VEGF protein. Basic fibroblast growth factor was expressed only in HL-60 cells and in only 3 of 4 fresh AML samples. These observations suggest that angiogenesis may play a role in the pathogenesis of AML. Inhibition of angiogenesis could constitute a novel strategy for the treatment of AML. (Blood. 2000;95:309-313).

Comparison of DNA ploidy, histologic, and immunohistochemical findings with clinical outcome in inflammatory myofibroblastic tumors.

Inflammatory myofibroblastic tumors (IMTs) are uncommon spindle cell proliferations that occur in the viscera and soft tissue of children and young adults. Their biologic potential is indeterminate: 25% of IMTs recur, and rare examples undergo malignant transformation (MT). This study investigates histologic features, DNA ploidy, and expression of apoptotic regulatory and oncogenic proteins in IMTs in an attempt to identify those deviances that might correlate with aggressive behavior or MT. Twenty-four formalin-fixed, paraffin-embedded IMTs for which clinical outcome was known were evaluated for cellularity, cytologic atypia, mitoses, ganglion-like cells, inflammatory infiltrate, DNA ploidy by flow cytometric examination, and bax, bcl-2, p53, and c-myc expression by immunohistochemical analysis. Sixteen (67%) of the IMTs did not recur, 6 (25%) recurred, and 2 (8%) underwent MT. Cellular atypia was observed in 69% of the cases without recurrence, 100% with recurrence, and 100% with MT. Ganglion-like cells were present in 56, 100, and 100% of the IMTs without recurrence, with recurrence, and with MT, respectively. There was no difference in the degree of cellularity, mitoses, or inflammatory infiltrate among the outcome groups. All of the tumors expressed bax, and none expressed c-myc. Two (8%) were immunoreactive for p53, one of which recurred and one of which underwent MT. bcl-2 expression was observed in 9 (37%) of the IMTs, with no difference among the three groups. Two IMTs were aneuploid, one of which underwent MT. Neither morphologic evaluation for cellularity, mitosis, or inflammatory infiltrate nor expression of bax or c-myc were useful for prediction of clinical outcome. The combination of atypia, ganglion-like cells, p53 expression and DNA ploidy analysis, however, might be useful to identify IMTs that might undergo MT or pursue a more aggressive clinical course with recurrences.

CD10 antigen expression correlates with the t(14;18)(q32;q21) major breakpoint region in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a common morphologic term for a biologically diverse group of lymphomas. The chromosome translocation, t(14;18)(q32;q21), and its associated bcl-2 gene rearrangement are generally associated with follicular lymphomas. Some investigators, however, proposed that the presence of the t(14;18) in DLBCL suggests a possible follicle center cell origin and might correlate with a higher relapse rate after therapy. The CD10 antigen is expressed in a majority of follicular lymphomas but is also seen occasionally in DLBCLs. In this study, we examined 26 DLBCLs for CD10 expression by flow cytometric analysis and tested them for the t(14;18)(q32;q21) major breakpoint region by a polymerase chain reaction-based method. bcl-2 protein expression was analyzed by an immunoperoxidase method. Of the 26 DLBCLs, 9 (35%) were CD10 positive. bcl-2 protein was expressed in 7 (78%) of 9 CD10-positive cases and in 9 (53%) of 17 CD10-negative cases (P = .4). The t(14; 18) translocation was present in 6 (67%) of 9 CD10-positive cases but in only 2 (17%) of 12 CD10-negative cases (P = .03). Five cases did not yield amplifiable DNA for analysis. In summary, no difference in bcl-2 protein expression was seen in CD10-positive versus CD10-negative DLBCLs, but CD10-positive DLBCLs were significantly more likely than CD10-negative DLBCLs to harbor the t(14;18) translocation. This suggests that CD10 might be a marker of follicle center cell origin in DLBCL.

Extramedullary plasmacytoma. A form of marginal zone cell lymphoma?

Extramedullary plasmacytoma (EMP), solitary plasmacytoma of bone, and multiple myeloma are related neoplasms, but EMP is clearly a distinct entity. Moreover, there are histologic and clinical similarities between EMP and marginal zone B-cell lymphomas (MZLs) displaying extensive plasma cell differentiation, suggesting a possible histogenetic relationship. The histologic and clinical features of 5 EMPs with extensive plasma cell differentiation were histologically reviewed for features of MZL. The previously diagnosed MZLs, mucosa-associated lymphoid tissue (MALT) type, of 2 patients also were reviewed. All patients were women aged 48 to 79 years. The EMPs originated in the parotid gland, lymph nodes, dura, or small bowel. The initial tumors diagnosed as MALT-type MZL were located in the lung and small bowel. All patients were treated with resection, with or without irradiation therapy. One patient also received systemic chemotherapy. All patients are alive with no evidence of disease. All tumors contained large numbers of plasma cells, constituting between 55% and 90% of the lymphoid cells. Centrocyte-like cells and monocytoid B cells each represented 0% to 25% of the infiltrate. Lymphoepithelial lesions were observed in all of the tumors in sites where epithelium was present. Reactive follicles were found in all of the tumors. EMPs may represent MZLs that have undergone an extensive degree of plasmacytic differentiation.

Risk factors in necrotizing fasciitis: a case involving Cryptococcus neoformans.

Necrotizing fasciitis is a destructive soft tissue infection that is most typically caused by group A streptococci or a combination of facultative and anaerobic bacteria. Patients at risk for the development of necrotizing fasciitis often have compromised immune function or poor tissue perfusion. This report describes a case of necrotizing fasciitis caused by Cryptococcus neoformans, a pathogen not previously associated with this primary destructive soft tissue infection. The process occurred in a patient at risk for the development of opportunistic infection. We briefly review the risk factors for the development of necrotizing fasciitis and the typical bacteriologic findings. Cryptococcal infections and their treatment are described. Despite the uncommon pathogen, the treatment of this patient followed established principles-prompt surgical intervention and systemic antimicrobial therapy tailored to the offending organisms.

The ASCP Resident Physician Section: results of surveys pertaining to "graduated responsibility for residents in anatomic pathology". American Society of Cytopathology.

Graduated responsibility for residents in anatomic pathology has been the subject of discussion among supervising staff and residents during the past few years. Presently a wide variation exists within pathology residency programs in the United States both in the degree of autonomy given to residents and in the areas of anatomic pathology (ie, surgical pathology, cytopathology, and autopsy pathology) within which the autonomy is granted. Recent surveys of supervising staff and residents have indicated a willingness to increase the level of independence for residents, especially at senior levels. Impediments include reimbursement, credentialing, and medicolegal issues. The results of the ASCP-Resident Physician Section (RPS) surveys pertaining to graduated responsibility for residents in anatomic pathology are discussed.

Resistant keratinocytes in 7,12-dimethylbenz[a]anthracene-initiated hamster buccal pouch epithelium.

In order to test the hypothesis that the property of resistance to cytotoxicity is an acquired trait of premalignant oral mucosal epithelium, cell dissociates were prepared from in vivo initiated hamster buccal pouch epithelium (HBPE), non-initiated HBPE and malignant HBPE cell lines. These cell types were evaluated for resistance to the cytotoxic effects of the inducing carcinogen, 7,12-dimethylbenz[a]anthracene (DMBA). A mitoinhibition assay and a clonogenicity assay were used to assess the ability of these cells to replicate or form colonies in the presence of 40 microM DMBA. Replication of primary plated HBPE cells was inhibited by 100% in both assays. PO II, a cell line derived from non-initiated, paraffin-oil-exposed HBPE, was inhibited by 97 and 100% in the mitoinhibition and colony-forming assays respectively. This same cell line, like primary plated HBPE, lacked the transformation-linked traits of angiogenesis and anchorage-independent growth. By contrast, three malignant HBPE cell lines, two derived during long-term culture of DMBA-initiated HBPE, and one from a DMBA-induced HBPE carcinoma, were inhibited by only 34% or less in the assays for resistance to cytotoxicity. Primary cell cultures derived from HBPE initiated in vivo with twice-weekly topical applications of a 0.5% solution of DMBA in paraffin oil, for 3 or 5 weeks, were inhibited to an intermediate degree, indicating the presence of DMBA-resistant cells. In addition, DMBA-resistant cell colonies were observed in cell cultures prepared at 2, 6 and 10 weeks after completing the 5 week initiation regimen. Progenitors of the resistant cells, persisting in vivo for several weeks after initiation, may represent early preneoplastic cell populations in this experimental model.