Rhabdomyosarcomas are a heterogeneous group of tumors with respect to their molecular basis, degree of differentiation, histology, and clinical behavior. Because of the wide variation of tumor morphology, it is often difficult to distinguish between the distinct subtypes of rhabdomyosarcomas. By using cryosections of tumor specimens and immunohistochemistry, in the present study we show that strong expression of myogenin in rhabdomyosarcoma is associated with alveolar histology (P ؍ <0.0001, Fisher's exact test). Although staining for myogenin was observed in 22 of 26 rhabdomyosarcomas, all alveolar rhabdomyosarcomas (nine of nine) showed high levels of staining for myogenin, as defined by the frequency and intensity of staining of the tumor cells. The staining pattern suggests that the tumor cells are clonally derived from myogenin-positive progenitor cells. In contrast, most embryonal rhabdomyosarcomas (13 of 15) were either negative or showed a low level of staining for myogenin. In these tumors a larger proportion of tumor cells were distinctly negative for myogenin. Six of seven alveolar rhabdomyosarcomas that strongly stained for myogenin were also positive for Pax3-7/Forkhead (FKHR) by polymerase chain reaction/reverse transcriptase-polymerase chain reaction. One of two embryonal rhabdomyosarcomas that strongly stained for myogenin was retrospectively found to be positive for Pax3/FKHR transcripts. Quantitative analysis for myogenin by Western blotting using a smaller subset of rhabdomyosarcomas revealed that in general there was a good correlation between immunohistochemical staining and Western blotting (P ؍ 0.01, Pearson Correlation), although the former technique was more sensitive for detecting tumors with low levels of the protein. On average, alveolar rhabdomyosarcomas expressed at least threefold more myogenin than embryonal rhabdomyosarcomas. Our data show that staining for myogenin will be a simple, rapid, and accurate adjunct for distinguishing between alveolar and embryonal rhabdomyosarcomas. We propose that embryonal rhabdomyosarcomas result from an early block in myogenesis, before the expression of myogenin. In contrast, we propose that alveolar rhabdomyosarcomas either originate from a late block in myogenesis (after expression of myogenin) or that the pathological mechanisms involved in these neoplasms also induce strong expression of this protein. Rhabdomyosarcomas are malignant myogenous tumors that can occur in any part of the body, including both skeletal muscle tissue and sites that are devoid of muscle. 1 These tumors are highly heterogeneous, not only with respect to their clinical behavior, but also with respect to the tumor morphology and spectrum of differen-
To evaluate the accuracy and reproducibility of subgrouping and grading soft-tissue sarcomas by fine-needle aspiration biopsy (FNAB), a blind review was conducted of 84 FNAB specimens from 77 malignant and 7 benign soft-tissue lesions. Cytomorphologic subgroups included 31 spindle-cell, 24 pleomorphic, 11 myxoid, 7 epithelioid/polygonal, 3 small round cell, and 8 nondiagnostic cases. Malignancies included one lymphoma and 41 primary, 15 recurrent, and 20 metastatic soft-tissue sarcomas. Adequacy was defined as a majority of slides with at least 5 clusters of 10 unobscured cells. Five originally false-negative cases were considered nondiagnostic on review. Sarcoma was recognized in 59 of 64 adequate cases (92%) with available histology; however, the specific histopathologic subtype was identified in only 9 cases (14%). Benign myxoid and spindle-cell lesions were difficult to separate from low-grade sarcomas in 4 cases, and a B-cell lymphoma with sclerosis mimicked a low-grade myxoid sarcoma. The assigned cytologic grade accurately reflected the histologic grade in 90% of sarcomas when segregated into high and low grades. Pleomorphic, small round cell, and epithelioid/polygonal subgroups corresponded to high-grade sarcomas in all cases with only minor noncorrelations. Major grading noncorrelations occurred in 50% of myxoid and 9% of spindle-cell sarcomas. Therefore, attention should be given to specimen adequacy, and caution should be exercised when attempting to grade myxoid and spindle-cell sarcomas by FNAB.
Identifying malignant plasma cells in body fluids from multiple myeloma patients is important for therapeutic and prognostic considerations. This can be difficult when plasma cells are mature in appearance or low in number. We examined the cytological and flow cytometric findings of myelomatous pleural and pericardial effusions from 8 patients with advanced multiple myeloma. Cytoplasmic immunoglobulin light chain excess vs. DNA ploidy in the plasma‐cell population was evaluated by flow cytometry (FCM). The cytology smears of one pericardial and 14 pleural effusions from the 8 patients were reviewed. Screening Papanicolaou‐stained smears facilitated the detection of malignant nuclear features; however, morphology of plasma cells was best seen in Diff‐Quik‐stained smears. Low cellularity and inadequate air‐drying of smears accounted for the false‐negative cytology seen in two fluids from a single patient. A malignant plasma cell population was identified in 9 of 10 fluids submitted for FCM, including the two fluids with negative cytology. The false‐negative FCM was from a suboptimal specimen with high background staining. Six fluids had an aneuploid DNA content, and four were diploid. A combination of Papanicolaou‐ and Diff‐Quik‐stained smears is recommended for the evaluation of plasma cells in effusions from patients with multiple myeloma. Cytology and flow cytometry confirmed malignancy in 87% and 90% of fluids evaluated, respectively; all cases were diagnosed by either one or both methods. Our results suggest that FCM and cytology of serous effusions in multiple myeloma patients are complementary and should be used in difficult cases. Diagn. Cytopathol. 2000;22:147–151. © 2000 Wiley‐Liss, Inc.
Identifying malignant plasma cells in body fluids from multiple myeloma patients is important for therapeutic and prognosticconsiderations. This can be diffıcult when plasma cells are mature in appearance or low in number. We examined the cytological and flow cytometric findings of myelomatous pleural and pericardial effusions from 8 patients with advanced multiple myeloma. Cytoplasmic immunoglobulin light chain excess vs. DNA ploidy in the plasma-cell population was evaluated by flow cytometry (FCM). The cytology smears of one pericardial and 14 pleural effusions from the 8 patients were reviewed. Screening Papanicolaou-stained smears facilitated the detection of malignant nuclear features; however, morphology of plasma cells was best seen in Diff-Quikstained smears. Low cellularity and inadequate air-drying of smears accounted for the false-negative cytology seen in two fluids from a single patient. A malignant plasma cell population was identified in 9 of 10 fluids submitted for FCM, including the two fluids with negative cytology. The false-negative FCM was from a suboptimal specimen with high background staining. Six fluids had an aneuploid DNA content, and four were diploid. A combination of Papanicolaou-and Diff-Quik-stained smears is recommended for the evaluation of plasma cells in effusions from patients with multiple myeloma. Cytology and flow cytometry confirmed malignancy in 87% and 90% of fluids evaluated, respectively; all cases were diagnosed by either one or both methods. Our results suggest that FCM and cytology of serous effusions in multiple myeloma patients are complementary and should be used in diffıcult cases.
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