Comparative evaluation of flow-cytometric immunophenotyping and immunocytochemistry in the categorization of malignant small round cell tumors in fine-needle aspiration cytologic specimens

Gautam, Upasana; Srinivasan, Radhika; Rajwanshi, Arvind; Bansal, Deepak; Marwaha, Ram Kumar

doi:10.1002/cncr.23948

Cited by 32 publications

(32 citation statements)

References 49 publications

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“…In line with our observations such studies showed that RMS cells typically display a CD45 − , CD56 + , CD90 + , nu myogenin + phenotype with variable expression of CD57, desmin, vimentin and CD99 [31], [36], [39], [41]. Unfortunately, in these studies, these and other markers (e.g.…”

Section: Discussionsupporting

confidence: 80%

“…Until now, few studies have been reported which evaluate the utility of MFC immunophenotyping for the diagnostic screening and subclassification of pediatric solid tumors [11]–[13], [27]–[28], [31], [35]–[39], [41], [48]–[51] Noteworthy, a relatively low (59%) concordance rate between immunophenotyping of fine-needle aspirated specimens by flow-cytometry and conventional cytological analyses has been reported, due to low sample cellularity [36]. Interestingly, here we obtained enough viable cells in every sample analyzed by using mechanical disaggregation procedures of freshly-obtained and processed samples, supporting the notion that mechanical disaggregation keeps antigen expression together with an acceptable cell viability [16]–[18], [52].…”

Section: Discussionmentioning

confidence: 99%

“…Despite all the above, preliminary studies have shown that neuroendocrine tumors display a CD45 − /CD56 + phenotype [32]–[35]; in turn, tumor cells from neuroblastoma coexpress GD2 [35], whereas primitive neuroectodermal tumors (PNET) coexpress CD57 and CD99, as well as CD56 [31], [34], [36]–[38], and rhabdomyosarcoma tumor cells are myogenin + [31], [39]–[41]. Despite this, the specificity of these phenotypes among the distinct subtypes of pediatric solid tumors remains to be established, and no study has been reported so far, in which a comprehensive panel of markers aimed at diagnostic screening, differential diagnosis and classification of distinct types of pediatric tumors, has been proposed and evaluated.…”

Section: Introductionmentioning

confidence: 99%

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Contribution of Multiparameter Flow Cytometry Immunophenotyping to the Diagnostic Screening and Classification of Pediatric Cancer

et al. 2013

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Pediatric cancer is a relatively rare and heterogeneous group of hematological and non-hematological malignancies which require multiple procedures for its diagnostic screening and classification. Until now, flow cytometry (FC) has not been systematically applied to the diagnostic work-up of such malignancies, particularly for solid tumors. Here we evaluated a FC panel of markers for the diagnostic screening of pediatric cancer and further classification of pediatric solid tumors. The proposed strategy aims at the differential diagnosis between tumoral vs. reactive samples, and hematological vs. non-hematological malignancies, and the subclassification of solid tumors. In total, 52 samples from 40 patients suspicious of containing tumor cells were analyzed by FC in parallel to conventional diagnostic procedures. The overall concordance rate between both approaches was of 96% (50/52 diagnostic samples), with 100% agreement for all reactive/inflammatory and non-infiltrated samples as well as for those corresponding to solid tumors (n = 35), with only two false negative cases diagnosed with Hodgkin lymphoma and anaplastic lymphoma, respectively. Moreover, clear discrimination between samples infiltrated by hematopoietic vs. non-hematopoietic tumor cells was systematically achieved. Distinct subtypes of solid tumors showed different protein expression profiles, allowing for the differential diagnosis of neuroblastoma (CD56hi/GD2+/CD81hi), primitive neuroectodermal tumors (CD271hi/CD99+), Wilms tumors (>1 cell population), rhabdomyosarcoma (nuMYOD1+/numyogenin+), carcinomas (CD45−/EpCAM+), germ cell tumors (CD56+/CD45−/NG2+/CD10+) and eventually also hemangiopericytomas (CD45−/CD34+). In summary, our results show that multiparameter FC provides fast and useful complementary data to routine histopathology for the diagnostic screening and classification of pediatric cancer.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Contribution of Multiparameter Flow Cytometry Immunophenotyping to the Diagnostic Screening and Classification of Pediatric Cancer

et al. 2013

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“…With increased use of molecular techniques, it has been noted that tumors with proven molecular diagnosis can exhibit unusual patterns of immunohistochemical staining[2] Gautam et al .,[10] in their study of 37 cases on flow cytometric immunophenotyping and immunocytochemistry in the categorization of malignant small round cell tumors found positivity for markers in addition to what usually is expected in three cases on immunocytochemistry and in four cases on immunophenotyping. They attributed it to divergent differentiation in malignant small round cell tumors.…”

Section: Discussionmentioning

confidence: 99%

FNA diagnosis of CD99 positive neuroblastoma: A diagnostic dilemma

Kaur

Bakshi

Verma

2012

J Cytol

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Tissue diagnosis of small round cell tumors relies heavily on immunohistochemical staining. Two of the small round cell tumors, namely neuroblastoma and primitive neuroectodermal tumor, have considerable morphologic overlap. Many studies suggest that CD99 positivity virtually excludes the diagnosis of neuroblastoma. We report a case of poorly differentiated neuroblastoma in which aberrant CD99 positivity led to diagnostic dilemma.

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“…Additionally, detection by FCM of minimal residual RMS cells in the BM during therapy to enable an evaluation of the efficacy of therapy has not been reported. Previous studies have shown that RMS cells typically exhibit a cluster of differentiation (CD)45 − /CD56 + /CD90 + /myogenin + phenotype with variable expression of CD57, desmin, vimentin and CD99 in fine-needle aspiration cytological specimens (8). Bozzi et al (9) previously reported that tricolor FCM detection of the CD56 + /CD90 + /CD45 − immunophenotype is extremely useful for the diagnosis of BM metastasis in patients with RMS, but the efficacy of FCM in monitoring therapeutic effects during and/or after chemotherapy has not been previously evaluated.…”

Section: Introductionmentioning

confidence: 99%

Staging and monitoring of childhood rhabdomyosarcoma with flow cytometry

et al. 2014

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Patients with metastatic rhabdomyosarcoma (RMS) have a poor prognosis. The detection of contaminating RMS cells in the bone marrow (BM) is important in clinical staging and risk assessment. The cytological examination of the BM remains the gold standard for the diagnosis of RMS, but has a limited sensitivity. In the present study, 32 BM and two cerebrospinal fluid (CSF) samples from 11 patients with suspected metastasis were analyzed by flow cytometry (FCM) with ganglioside D2 (GD2) conjugated with fluorescein isothiocyanate, cluster of differentiation (CD)90-phycoerythrin, CD45-peridinin chlorophyll protein and CD56-allophycocyanin monoclonal antibody cocktail in parallel to morphological examination at diagnosis or during treatment. Five samples (14.7%) were positive for RMS onup morphological examination. By FCM, 16 samples (47.1%) were positive for RMS. A significant difference was identified between the two methods. The four-color FCM assay successfully detected RMS cells in BM samples to a level of 0.01% (1 per 104 cells). RMS cells demonstrated a phenotype with CD56+/CD90+/CD45−/GD2− expression, which is different from the CD56+/CD90+/CD45−/GD2+ expression phenotype in neuroblastoma cells. The follow-up of four patients by FCM demonstrated that two patients became minimal residual disease-negative following two and four cycles of chemotherapy, respectively, and survived. The other two cases remained FCM-positive despite receiving four courses of chemotherapy and consequently succumbed to progressive disease. In addition, FCM analysis of the CSF samples from one patient confirmed a diagnosis of CSF metastasis with RMS. In conclusion, FCM may have a role not only in staging and monitoring the effects of therapy, but also in providing diagnostic confirmation of CSF metastasis with RMS.

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Comparative evaluation of flow-cytometric immunophenotyping and immunocytochemistry in the categorization of malignant small round cell tumors in fine-needle aspiration cytologic specimens

Abstract: FCI is applicable on FNA material and complements ICC in accurate the typing of MSRCTs. This is particularly useful in advanced-stage disease, when neoadjuvant chemotherapy may be instituted promptly.

Cited by 32 publications

References 49 publications

Contribution of Multiparameter Flow Cytometry Immunophenotyping to the Diagnostic Screening and Classification of Pediatric Cancer

Contribution of Multiparameter Flow Cytometry Immunophenotyping to the Diagnostic Screening and Classification of Pediatric Cancer

FNA diagnosis of CD99 positive neuroblastoma: A diagnostic dilemma

Staging and monitoring of childhood rhabdomyosarcoma with flow cytometry

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