Small Round Cell Malignant Tumors Research Articles

Renal CIC-LEUTX rearranged sarcoma with multiple pulmonary metastases: a case report and literature review

BackgroundCIC-rearranged sarcomas (CRS) are a group of heterogeneous tumors which mostly occur in the soft tissues of limbs and trunk, and are highly invasive with poor prognosis. Here, we describe a rare case of CRS that occurred in the left kidney with a CIC-LEUTX rearrangement.Case presentationA 45-year-old male was admitted to hospital with a dry cough for more than two months without obvious cause. Physical examination and laboratory tests revealed no notable abnormality. The CT scan demonstrated a mass in the left kidney and multiple nodules in both lungs. The percutaneous core needle biopsy showed similar histomorphology and immunophenotype of small round cell malignant tumors. Genetic test revealed a CIC-LEUTX gene fusion.ConclusionsWe present a rare primary renal CRS with multiple pulmonary metastases, and LEUTX is confirmed as the fusion partner of CIC gene for the first time in a renal case.

Primary Nodal Merkel Cell Carcinoma: Rare Presentation

Merkel cell carcinoma (MCC) is a very rare high-grade neuroendocrine carcinoma that is frequently located in the skin. Although most cases are associated with Merkel cell polyomavirus, there are also cases in which the virus cannot be detected. The purpose of presenting the case of MCC with primary nodal involvement is due to its rare presentation. 
 A 59-year-old male patient presented to the hospital with painless mass in the neck. Imaging analyses revealed necrotic lymphadenopathies on the neck, measuring up to 4.5 cm in size. After an explorative surgery with preliminary diagnoses of lymphoma and squamous cell carcinoma , samples taken from the excised mass showed high-grade neuroendocrine carcinoma morphology. In addition to neuroendocrine markers, CK7 and CK20 positivity were observed in the immunohistochemical tests performed. As a result, the case was evaluated in favor of MCC with negativity of markers performed to exclude other malignancies. Subsequently, a diagnosis of primary nodal MCC was made due to the absence of a different focus other than lymph node on PET imaging analysis.
 The differential diagnosis should be kept broad due to the histopathological morphology of small round cell malignant tumors. In addition in high-grade neuroendocrine carcinomas, the possibility of MCC should be ruled out especially if CK20 positivity is present. Although is has been reported that primary nodal MCC cases have a better clinical course compared to nodal metastatic cases with a known primary, there are limited case series studies on this topic. A multisystem approach is recommended for proper clinical management.

Expression and diagnostic value of NKX3.1 and NKX2.2 in mesenchymal chondrosarcoma

Objective: To investigate the immunohistochemical expression of NKX3.1 and NKX2.2 in mesenchymal chondrosarcoma (MC), and to explore the differential diagnostic value of NKX3.1 and NKX2.2 in MC and other types of small round cell malignant tumors. Methods: A total of 12 cases of MC and 97 other small round cell malignant tumors diagnosed in Jinling Hospital, Nanjing University School of Medicine from 2001 to 2020 were collected for NKX3.1 and NKX2.2 immunohistochemical detection. Among them, two kinds of NKX3.1 antibodies [rabbit polyclonal antibody and rabbit monoclonal antibody (EP356)] were used for detection in 12 cases of MC, and one NKX3.1 antibody (rabbit polyclonal antibody) was detected in 97 cases of other small round cell malignant tumors, and the relevant literature was reviewed. Results: The 12 MC patients included 7 females and 5 males, with a mean age of 33 years (14-54 years). Nine cases were from bone and three from soft tissue. Among the 12 MC patients, 8 patients had postoperative recurrence or metastasis, and 3 of them died of tumor recurrence or metastasis. Histologically, 12 cases of MC showed typical bidirectional differentiation.The positive rate of both NKX3.1 antibodies in MC was 12/12, NKX3.1 was focal weakly positive in only one of 12 chondrosarcomas (grade 3), 5 alveolar rhabdomyosarcomas, 5 embryonal rhabdomyosarcomas, and 5 solitary fibrous tumors, respectively. The remaining 70 cases of other small round cell malignant tumors were negative. The positive rates of NKX2.2 in MC, Ewing sarcoma and olfactory neuroblastoma were 12/12, 15/15 and 4/5, respectively. In 12 cases of chondrosarcoma (grade 3), 5 cases of poorly differentiated synovial sarcoma, 5 cases of alveolar rhabdomyosarcoma, and 5 cases of solitary fibrous tumor, NKX2.2 was focally and weakly positive in only one case, respectively, and all the remaining 50 cases of other small round cell malignant tumors were negative. Conclusions: The expression of NKX3.1 and NKX2.2 proteins are significant indicators in the diagnosis of MC, and the combined detection of NKX3.1 and NKX2.2 can help distinguish MC from most other small round cell malignant tumors.

Machine learning to differentiate small round cell malignant tumors and non-small round cell malignant tumors of the nasal and paranasal sinuses using apparent diffusion coefficient values

ObjectiveWe used radiomics feature–based machine learning classifiers of apparent diffusion coefficient (ADC) maps to differentiate small round cell malignant tumors (SRCMTs) and non-SRCMTs of the nasal and paranasal sinuses.MaterialsA total of 267 features were extracted from each region of interest (ROI). Datasets were randomized into two sets, a training set (∼70%) and a test set (∼30%). We performed dimensional reductions using the Pearson correlation coefficient and feature selection analyses (analysis of variance [ANOVA], relief, recursive feature elimination [RFE]) and classifications using 10 machine learning classifiers. Results were evaluated with a leave-one-out cross-validation analysis.ResultsWe compared the AUC for all the pipelines in the validation dataset using FeAture Explorer (FAE) software. The pipeline using RFE feature selection and Gaussian process classifier yielded the highest AUCs with ten features. When the “one-standard error” rule was used, FAE produced a simpler model with eight features, including Perc.01%, Perc.10%, Perc.90%, Perc.99%, S(1,0) SumAverg, S(5,5) AngScMom, S(5,5) Correlat, and WavEnLH_s-2. The AUCs of the training, validation, and test datasets achieved 0.995, 0.902, and 0.710, respectively. For ANOVA, the pipeline with the auto-encoder classifier yielded the highest AUC using only one feature, Perc.10% (training/validation/test datasets: 0.886/0.895/0.809, respectively). For the relief, the AUCs of the training, validation, and test datasets that used the LRLasso classifier using five features (Perc.01%, Perc.10%, S(4,4) Correlat, S(5,0) SumAverg, S(5,0) Contrast) were 0.892, 0.886, and 0.787, respectively. Compared with the RFE and relief, the results of all algorithms of ANOVA feature selection were more stable with the AUC values higher than 0.800.ConclusionsWe demonstrated the feasibility of combining artificial intelligence with the radiomics from ADC values in the differential diagnosis of SRCMTs and non-SRCMTs and the potential of this non-invasive approach for clinical applications.Key Points• The parameter with the best diagnostic performance in differentiating SRCMTs from non-SRCMTs was the Perc.10% ADC value.• Results of all the algorithms of ANOVA feature selection were more stable and the AUCs were higher than 0.800, as compared with RFE and relief.• The pipeline using RFE feature selection and Gaussian process classifier yielded the highest AUC.

Texture Analysis of Fat-Suppressed T2-Weighted Magnetic Resonance Imaging and Use of Machine Learning to Discriminate Nasal and Paranasal Sinus Small Round Malignant Cell Tumors.

ObjectiveWe used texture analysis and machine learning (ML) to classify small round cell malignant tumors (SRCMTs) and Non-SRCMTs of nasal and paranasal sinus on fat-suppressed T2 weighted imaging (Fs-T2WI).MaterialsPreoperative MRI scans of 164 patients from 1 January 2018 to 1 January 2021 diagnosed with SRCMTs and Non-SRCMTs were included in this study. A total of 271 features were extracted from each regions of interest. Datasets were randomly divided into two sets, including a training set (∼70%) and a test set (∼30%). The Pearson correlation coefficient (PCC) and principal component analysis (PCA) methods were performed to reduce dimensions, and the Analysis of Variance (ANOVA), Kruskal-Wallis (KW), and Recursive Feature Elimination (RFE) and Relief were performed for feature selections. Classifications were performed using 10 ML classifiers. Results were evaluated using a leave one out cross-validation analysis.ResultsWe compared the AUC of all pipelines on the validation dataset with FeAture Explorer (FAE) software. The pipeline using a PCC dimension reduction, relief feature selection, and gaussian process (GP) classifier yielded the highest area under the curve (AUC) using 15 features. When the “one-standard error” rule was used, FAE also produced a simpler model with 13 features, including S(5,-5)SumAverg, S(3,0)InvDfMom, Skewness, WavEnHL_s-3, Horzl_GlevNonU, Horzl_RLNonUni, 135dr_GlevNonU, WavEnLL_s-3, Teta4, Teta2, S(5,5)DifVarnc, Perc.01%, and WavEnLH_s-2. The AUCs of the training/validation/test datasets were 1.000/0.965/0.979, and the accuracies, sensitivities, and specificities were 0.890, 0.880, and 0.920, respectively. The best algorithm was GP whose AUCs of the training/validation/test datasets by the two-dimensional reduction methods and four feature selection methods were greater than approximately 0.800. Especially, the AUCs of different datasets were greater than approximately 0.900 using the PCC, RFE/Relief, and GP algorithms.ConclusionsWe demonstrated the feasibility of combining artificial intelligence and the radiomics from Fs-T2WI to differentially diagnose SRCMTs and Non-SRCMTs. This non-invasive approach could be very promising in clinical oncology.

Clinicopathological characteristics of SMARCB1(INI1)-deficient sinonasal carcinoma

Objective: To investigate the clinicopathological characteristics, diagnosis, differential diagnosis and prognostic factors of SMARCB1 (INI1)-deficient sinonasal carcinoma (SDSC). Methods: Sixteen cases of SDSC diagnosed in the Department of Pathology, Beijing Tongren Hospital from January 2016 to September 2020 were enrolled. Ninety-nine cases of small round cell malignant tumors of the head and neck were selected as the control, including poorly-differentiated squamous cell carcinoma (n=10), poorly-differentiated adenocarcinoma (n=5), undifferentiated carcinoma (SNUC, n=4), NUT carcinoma (n=5), neuroendocrine carcinoma (n=10), and other non-epithelial tumors [olfactory neuroblastoma (n=10), rhabdomyosarcoma (n=10), NK/T-cell lymphoma (n=10), malignant melanoma (n=10), Ewing's sarcoma/primitive neuroectodermal tumor (EWS/PNET, n=5)] and non-keratinizing undifferentiated nasopharyngeal carcinoma (n=20). The clinical and pathologic characteristics of SDSC, and immunohistochemical (IHC) expression of broad-spectrum CKpan, CK7, CK8/18, CK5/6, p63, p40, p16, INI1, NUT and neuroendocrine markers (Syn, CgA, CD56) were evaluated. In situ hybridization (ISH) was used to detect EBER and fluorescence in situ hybridization (FISH) to detect INI1 gene deletion. Results: The 16 cases of SDSC accounted for 1.3% (16/1 218) of all malignant sinonasal tumors in the author's unit during this time period, and 2.4% (16/657) of all malignant epithelial tumors. Microscopically, there was no clear squamous and adenomatous differentiation, but "rhabdoid-like" cells, are often seen. All SDSC cases were positive for CKpan and CK8/18, negative for INI1; Epstein-Barr virus was not detected by ISH; and INI1 gene deletion was observed in all 11 SDSC patients with FISH. Twelve cases were followed up for 3-47 months. One died of tumor-related diseases half a year after diagnosis, and the remaining patients were alive with tumor, the longest survival time was 47 months. Conclusion: SDSC should be differentiated from a variety of poorly-differentiated tumors in the sinonasal area. Histologically, SDSC has no clear differentiation, but the tumor cells are characteristically basal-like or rhabdoid-like, with non-specific vacuoles, translucent or vacuolar nuclei, prominent nucleoli and necrotic foci. They are negative for INI1 IHC staining, and FISH demonstrates INI1 gene deletion. The clinical prognosis is still unclear, further studies on its biologic behavior and treatment methods are warranted.

Diagnosis and treatment of supratentorial tumors with small round cell malignancies diagnosed by intraoperative rapid pathology

Objective To explore the diagnosis and treatment of supratentorial tumors with small round cell malignancies diagnosed by intraoperative rapid pathology. Methods A retrospective analysis was conducted on the clinical data of 36 patients with supratentorial tumors diagnosed as small round cell malignant tumors by intraoperative frozen pathology at Department of Neurosurgery, Nanfang Hospital, Southern Medical University from January 2011 to December 2017. All patients were treated with complete tumor resection according to the principle of glioma operation. After the operation, the MRI of the head was reexamined, and the volume quantitative analysis was used to determine the degree of tumor resection, which was divided into complete resection, subtotal resection and partial resection. All patients were followed up regularly in outpatient department, and MRI was reexamined to explore the recurrence of tumor. Results MRI of 36 patients after operation showed that 31 patients (86.1%) had complete resection and 5 patients (13.9%) had subtotal resection. The results of pathological diagnosis were as follows: primary central nervous system lymphoma (10 cases), glioblastoma (6 cases), central neurocytoma (5 cases), primitive neuroectodermal tumors (3 cases), brain metastasis tumor (2 cases), pineal cell tumors(2 cases), ependymoblastoma (2 cases), World Health Organization (WHO) grade Ⅱ glioma (2 cases), pituitary adenoma (1 case), periangioblastoma (1 case), olfactory neuroblastoma(1 case) and desmoplastic small round cell tumor (1 case). Among the 33 patients diagnosed by MRI before operation, 8 (24.2%) had the same pathological results with preoperative diagnosis, including 4 cases of lymphoma, 1 case of central neurocytoma, 1 case of primitive neuroectodermal tumor, 1 case of hemangioblastoma and 1 case of metastasis. The follow-up duration of 36 patients was 28.9±8.1 months and ranged from 6 to 70 months . During the follow-up period, 26 out of 36 patients (72.2%) relapsed. Conclusions The supratentorial tumors with small round cell malignant tumor diagnosed by rapid pathology during operation should be resected in the maximal range under the premise of safety, the pathological results are various and its therapeutic effect seems relatively good. Key words: Supratentorial tumor; Pathology; Treatment outcome; In operation; Small round cell tumor

Intraspinal metastasis of alveolar rhabdomyosarcoma: A case report

This paper reported a case of cervical intraspinal metastasis of alveolar rhabdomyosarcoma (ARMS). The clinicopathological features, surgical treatment, chemotherapy and prognosis were introduced and the current literature was reviewed. The diagnosis, differential diagnosis, treatment, molecular features and prognosis of the disease were comprehensively analyzed to improve clinicians' knowledge of this rare disease. The primary lesion appeared about 1 year ago which was painless mass of left hand whose size was about 2 cm×2 cm. After conservative treatment, the mass gradually enlarged and the mass was resected. Postoperative pathology revealed embryonic rhabdomyosarcoma. Postoperative chemotherapy with recombinant human endostatin, liposomal doxorubicin and ifosfamide was performed. The left neck mass was found about 3 months ago, and then the left neck mass was resected under general anesthesia. Postoperative pathological examination showed small round cell malignant tumors. Severe left upper extremity pain began about 2 weeks ago with nocturnal pain and supine pain. Non-steroidal anti-inflammatory drugs were needed to relieve pain which was accompanied by numbness and weakness of the left upper extremity. MRI showed a intraspinal tumor at C5. The left thumb and index finger were absent. Hypoesthesia, muscle atrophy and hypotonia of the left upper limb were confirmed. The muscle strength of biceps brachii and deltoid muscle of the left upper limb was grade 0, the muscle strength of extensor carpus and interphalangeal muscle was grade II, the muscle strength of intrinsic muscles of hands was grade I. The tendon reflex of the left upper limb disappeared. Intraspinal mass was removed and the pain was relieved. But there was no significant change in the muscle strength of the left upper limb. Pathological examination revealed small cell malignancies which were poorly differentiated with diffuse patchy distribution and disordered arrangement. The tumor cells had round, oval or irregular nuclei, and few cytoplasms were positive for Myogenin and MyoD1. FISH test of FOXO1 gene was positive. More than 50% of nuclei showed redgreen signal separation, and the distance between redgreen signals was larger than double diameter of the signal points, which supported ARMS. Total resection of intraspinal tumors was achieved and postoperative chemotherapy was admitted. But intraspinal disseminated metastasis occurred rapidly. ARMS was rare, aggressive tumor with poor prognosis. Subdural metastasis was rare. Correct diagnosis and classification can be made only with help of modern molecular diagnostic methods, which is effective to guide the treatment.

Utility of NUT gene expression and rearrangement in diagnosis of NUT midline carcinoma in upper respiratory tract

To investigate the importance of expression of the NUT gene and its rearrangement in diagnosing NUT midline carcinoma (NMC) of the upper respiratory tract; and to evaluate the prevalence, histological features and differential diagnosis of NMC of the upper respiratory tract. One-hundred and sixty-three small cell malignant tumors of the upper respiratory tract were reviewed at the Beijing Tongren Hospital, Capital Medical University over a 20-year period. These cases included poorly-differentiated squamous cell carcinomas (n = 31), undifferentiated carcinoma (n = 1), non-keratizing undifferentiated nasopharyneal carcinomas (n = 60), small cell neuroendocrine carcinomas (n = 6) and non-epithelial small round cell malignant tumors (n = 65). The clinical and pathologic features were investigated. All cases were subjected to Epstein-Barr virus encoded RNA (EBER) in situ hybridization and NUT monoclonal antibody immunohistochemical staining. Cases positive for NUT immunohistochemistry and negative for EBER in situ hybridization were submitted for fluorescent in situ hybridization (FISH) for rearrangements in both BRD4 and NUT genes, and immunohistochemical staining for a set of cytokeratins (AE1/AE3, CK7, CK8), p63,and neuroendocrine markers (NSE, Syn, CgA, S-100 protein, CD56). Three cases of poorly-differentiated squamous cell carcinomas and one case of undifferentiated carcinoma showed diffuse nuclear immunohistochemical staining with antibody against NUT. These positive cases approximately accounted for 12.5% (4/32) of this group, 4.1% (4/98) of the malignant epithelial carcinomas and 2.5% (4/163) of all small round cell malignant tumors in the study. The age of these patients were 42 - 59 years. Other groups were all negative for NUT immunohistochemistry. These four cases also stained for antibodies against cytokeratins and p63, but were negative for neuroendocrine markers and not associated with EBV infection. Only two of these four cases showed rearrangements of the NUT and BRD4 genes by FISH. These two patients died within one year. The other two patients that did not demonstrate NUT rearrangement by FISH were alive and did not have an aggressive clinical course, surviving 40 and 12 months respectively. NMC is a rare small round cell malignant tumor in the upper respiratory tract. Only in the groups of primary poorly differentiated squamous cell carcinoma and undifferentiated carcinoma were positive for NUT immunohistochemical staining and NUT rearrangement by FISH. NMC typically occurs in midline organs, and affects the sinonasal tract. It is not associated with EBV infection. There is difference in the clinical course and prognosis among NMC patients. NUT immunohistochemical staining and NUT gene rearrangement analysis can differentiate NMC from other small cell tumors in the upper respiratory tract.

Primary primitive neuroectodermal tumor of the orbit

Primitive neuroectodermal tumor (PNET) is a small round cell malignant tumor of neuroectodermal origin. Most of the PNETs occur in the central nervous system (CNS). PNETs recognized outside of CNS are diagnosed as peripheral PNET (pPNET). This tumor which expresses MIC-2 gene (CD99) seems to be least aggressive after complete tumor resection. We describe a rare case of PNET in a young girl.

Fine-needle aspiration biopsy diagnosis of small round cell tumors of childhood: A comprehensive approach.

Fine-needle aspiration biopsy findings in small round cell malignant tumors of children are briefly reviewed. All of these tumors usually have characteristic cytomorphology which, when recognized, may lead to a definitive diagnosis. However, when these tumors are undifferentiated, morphologic criteria may not be sufficient for arriving at a correct diagnosis. A variety of ancillary studies including electron microscopy, immunohistochemistry and DNA ploidy, cytogenetics, and fluorescent in situ hybridization may provide valuable additional information for precise characterization of these neoplasms. Some of the ancillary studies may also be used for assigning these cases to prognostically significant subgroups. This information may also help in defining the most suitable chemotherapeutic regimens for these tumors. Since most of these special studies require only a small amount of cellular material, fine-needle aspiration biopsy is ideally suited for obtaining samples for these procedures. It is hoped that as cytogenetic and molecular techniques become available in many diagnostic laboratories, a comprehensive evaluation of aspiration biopsies from round cell malignant tumors, encompassing a precise pathologic diagnosis, determination of prognosis, and prediction of response to therapy, will be possible in a majority of cases. Diagn. Cytopathol. 1999;21:81-91.