Clinical practice guidelines for the treatment of Ewing sarcoma (Spanish Sarcoma Research Group-GEIS).

Ewing sarcoma is a small round-cell sarcoma characterized by gene fusion involving EWSR1 (or another TET family protein like FUS) and an ETS family transcription factor. The estimated incidence of this rare bone tumor, which occurs most frequently in adolescents and young adults, is 0.3 per 100,000/year. Although only 25% of patients with Ewing sarcoma are diagnosed with metastatic disease, historical series show that this is a systemic disease. Patient management requires multimodal therapies-including intensive chemotherapy-in addition to local treatments (surgery and/or radiotherapy). In the recurrent/refractory disease setting, different approaches involving systemic treatments and local therapies are also recommended as well as patient inclusion in clinical trials whenever possible. Because of the complexity of Ewing sarcoma diagnosis and treatment, it should be carried out in specialized centers and treatment plans should be designed upfront by a multidisciplinary tumor board. These guidelines provide recommendations for diagnosis, staging, and multimodal treatment of Ewing sarcoma.

Retroperitoneal adrenal neuroblastoma with bone marrow metastatic activity in a young adult.

A 31-year-old male came to emergency department with acute abdominal pain from the right flank, diaphoresis and, palpitations. Contrasted abdominal CT revealed a tumor dependent from right adrenal gland and kidney. A laparoscopic radical nephrectomy was made to resect the tumor and pain relief. Pathological analysis reported poorly differentiated neuroblastoma from the right adrenal gland without involvement to kidney and ureter. The patient was sent to oncology clinic to continue with chemotherapy treatment. This is the third case of adult neuroblastoma reported in South America. Adult neuroblastoma is an uncommon cause of malignant neoplasm with an exceptional incidence reported.

[Desmoplastic round cell tumor]. / Tumor desmoplásico de células redondas.

Desmoplastic small round cell tumor is a rare and very aggressive neoplasm that belongs to the family of "small round blue cell tumors". It has a higher incidence in males in the second decade of life. It is due to translocation t(11;22) (p13;q12). It can be located both in the abdomen and in the retroperitoneum and is characterized by nonspecific symptoms. The treatment is very varied and the one that guarantees the total cure of the patient has not yet been detected. The objective of this study is to expose a clinical case of desmoplastic tumor as an rare abdominal disease and its imaging expression.

El tumor desmoplásico de células pequeñas y redondas es una neoplasia poco frecuente y muy agresiva que forma parte de la familia de los "tumores de células pequeñas, redondas y azules". Presenta una mayor incidencia en el sexo masculino en la segunda década de la vida. Se debe a la translocación t(11;22) (p13;q12). Se puede localizar tanto en el abdomen como en el retroperitoneo caracterizándose por presentar síntomas inespecíficos. El tratamiento es muy variado y no se ha detectado todavía aquel que garantice la cura total del paciente. El objetivo del presente estudio es exponer un caso clínico de tumor desmoplásico como enfermedad abdominal infrecuente y su expresión imagenológica.

Tumor desmoplásico de células redondas / Desmoplastic round cell tumor

Resumen El tumor desmoplásico de células pequeñas y redon das es una neoplasia poco frecuente y muy agresiva que forma parte de la familia de los "tumores de célu las pequeñas, redondas y azules". Presenta una mayor incidencia en el sexo masculino en la segunda década de la vida. Se debe a la translocación t(11;22) (p13;q12). Se puede localizar tanto en el abdomen como en el re troperitoneo caracterizándose por presentar síntomas inespecíficos. El tratamiento es muy variado y no se ha detectado todavía aquel que garantice la cura total del paciente. El objetivo del presente estudio es exponer un caso clínico de tumor desmoplásico como enfermedad abdo minal infrecuente y su expresión imagenológica.

Abstract Desmoplastic small round cell tumor is a rare and very aggressive neoplasm that belongs to the family of "small round blue cell tumors". It has a higher incidence in males in the second decade of life. It is due to trans location t(11;22) (p13;q12). It can be located both in the abdomen and in the retroperitoneum and is character ized by nonspecific symptoms. The treatment is very varied and the one that guarantees the total cure of the patient has not yet been detected. The objective of this study is to expose a clinical case of desmoplastic tumor as an rare abdominal disease and its imaging expression.

Intra-abdominal transmissible venereal tumor in a dog: a case report.

Transmissible venereal tumor (TVT) is a malignant round cell neoplasm that primarily affects the genital region of dogs. Despite being sexually transmitted, transmission can occur through contact with mucous membranes and cutaneous tissue. Although less routine, TVT has been described in several extragenital regions, such as the nasal plane, oral cavity, eyeball, eyelid, and anus. Although metastases are infrequent, they can occur in the skin, inguinal lymph nodes, liver, kidneys, spleen, intestine, heart, brain, lungs, and other organs. The clinical signs of TVT are usually related to serosanguineous secretion, intense odor, deformity, ulceration, and possibly areas of necrosis. In cases of metastases, clinical signs will depend on the affected organ. The treatment of choice for TVT is chemotherapy with vincristine. The present study aimed to report the case of a 2-year-old mixed-breed canine with intra-abdominal nodules detected by ultrasound examination, which were later diagnosed as a TVT by histopathology and immunohistochemistry.

O tumor venéreo transmissível (TVT) é uma neoplasia maligna de células redondas que acomete principalmente a região genital de cães. Apesar de ser sexualmente transmissível, a transmissão pode ocorrer através do contato com mucosas e tecidos da pele. Embora menos rotineiro, o TVT tem sido descrito em diversas regiões extragenitais, como plano nasal, cavidade oral, globo ocular, pálpebra e ânus. Embora as metástases sejam infrequentes, elas podem ocorrer na pele, linfonodos inguinais, fígado, rins, baço, intestino, coração, cérebro, pulmão e outros órgãos. Os sinais clínicos do TVT geralmente estão relacionados à secreção serossanguinolenta, odor intenso, deformidade, ulceração, podendo ou não haver áreas de necrose e, nos casos de metástases, os sinais clínicos vão depender do órgão acometido. O tratamento de escolha para TVT é a quimioterapia, com uso de vincristina. O presente trabalho tem como objetivo relatar o caso de um canino de dois anos de idade, sem raça definida, com nódulos intra-abdominais detectados ao exame ultrassonográfico, que posteriormente foram diagnosticados como tumor venéreo transmissível por meio de histopatologia e imunohistoquímica.

Canine transmissible venereal tumor with spontaneous remission: case study with emphasis on clinical and cytopathological exams to monitor tumor evolution / Tumor venéreo transmissível canino com remissão espontânea: estudo de caso com ênfase aos exames clínico e citopatológico para monitoramento da evolução tumoral

The canine transmissible venereal tumor (TVTC) is a neoplasm transmitted mainly through copulation and with a high incidence in stray dogs in Brazil. In the process of tumor evolution of TVTC, the progression, stationary and regression phases are recognized. The host immunity is related to the disease's biological behavior, however, spontaneous regression observation in cases of naturally occurring TVTC is uncommon. A canine patient was attended, after beeing rescued from the street, due to an ulcerated mass in the external genitália and tick infestation. Cytopathological examination, which diagnosed TVTC, and laboratory tests that showed mild anemia and severe thrombocytopenia were performed. In view of the impossibility of carrying out other exams, it was made the presumptive diagnosis of canine monocytic ehrlichiosis (CME), and treatment was instituted. During follow-up it was observed quick improvement in clinical signs and laboratory changes, as well as a reduction in tumor mass. A new cytopathological evaluation was carried out, and was verified increase in mature lymphocytes and plasmocytes in the midst of the tumor cells, finding compatible with the stationary phase of the disease. From that moment on, it was decided to perform only clinical and cytopathological follow-up. In the following evaluations, continuous clinical remission and cytopathological findings compatible with those described in the regression phase were observed, until its complete remission. It is considered that the improvement in the general health of the patient after the treatment of CME is related to the spontaneous regression of TVTC, and that simultaneous performance of serial clinical and cytopathological exams may be feasible and useful for monitoring the stages of evolution of TVTC.

O tumor venéreo transmissível canino (TVTC) é uma neoplasia transmitida principalmente através da cópula, com elevada incidência em cães errantes no Brasil. No processo de evolução tumoral do TVTC, são reconhecidas as fases de progressão, estacionária e de regressão. O estado imunológico do hospedeiro está relacionado ao comportamento biológico da doença, contudo, a observação de regressão espontânea em casos de TVTC de ocorrência natural é incomum. Foi atendida uma paciente canina, resgatada da rua, por apresentar massa ulcerada na genitália externa e infestação por carrapatos. Foram realizados exame citopatológico, que diagnosticou TVTC, e exames laboratoriais que evidenciaram anemia discreta e grave trombocitopenia. Com isso e diante da impossibilidade de realizar outros exames, foi também estabelecido o diagnóstico presuntivo de erlichiose monocítica canina (EMC) e instituído tratamento para a hemoparasitose. Durante o acompanhamento, foi observada rápida melhora dos sinais clínicos e das alterações laboratoriais, bem como a redução espontânea da massa tumoral. Em sequência, foi realizada nova avaliação citopatológica do TVTC e verificado o aumento quantitativo de linfócitos maduros e plasmócitos, em meio as células tumorais, achado compatível com a fase estacionária da doença. A partir desse momento, optou-se por realizar apenas acompanhamento clínico e avaliação citopatológica da neoplasia. Foram observados contínua remissão clínica e achados microscópicos compatíveis com a fase de regressão do tumor, até sua remissão completa. Pondera-se que a melhora na saúde geral da paciente após o tratamento da EMC esteja relacionada à regressão espontânea do TVTC, e que realização simultânea de exames clínico e citopatológico seriados pode ser viável e útil ao acompanhamento das fases de evolução do TVTC.

EWSR1-ATF1 Fusion in a Myoepithelial Carcinoma of Soft Tissue With Small Round Cell Morphology: A Potential Diagnostic Pitfall.

Myoepithelial tumors of soft tissue are rare mesenchymal neoplasms that overlap with their salivary gland and skin counterparts at both the histopathologic and molecular levels. EWSR1 gene rearrangements with various fusion partners represent a common genetic event in myoepithelial tumors of soft tissue, whether benign or malignant, and may prove useful as a diagnostic tool in difficult cases. However, the number of diagnostic entities with EWSR1 gene rearrangements has grown considerably in recent years, and there is significant morphologic and immunophenotypic overlap amongst this group, underscoring the importance of fusion testing to detect fusion partners that are characteristic of discrete diagnostic entities. Herein, we report a malignant myoepithelial tumor of soft tissue/myoepithelial carcinoma with an undifferentiated round cell morphology arising in a pediatric patient with a EWSR1-ATF1 gene fusion.

Desmoplastic Small Round Cell Tumor: A Review of Main Molecular Abnormalities and Emerging Therapy.

Desmoplastic small round cell tumor (DSRCT) is an extremely rare, aggressive sarcoma affecting adolescents and young adults with male predominance. Generally, it originates from the serosal surface of the abdominal cavity. The hallmark characteristic of DSRCT is the EWSR1-WT1 gene fusion. This translocation up-regulates the expression of PDGFRα, VEGF and other proteins related to tumor and vascular cell proliferation. Current management of DSRCT includes a combination of chemotherapy, radiation and aggressive cytoreductive surgery plus intra-peritoneal hyperthermic chemotherapy (HIPEC). Despite advances in multimodal therapy, outcomes remain poor since the majority of patients present disease recurrence and die within three years. The dismal survival makes DSRCT an orphan disease with an urgent need for new drugs. The treatment of advanced and recurrent disease with tyrosine kinase inhibitors, such as pazopanib, sunitinib, and mTOR inhibitors was evaluated by small trials. Recent studies using comprehensive molecular profiling of DSRCT identified potential therapeutic targets. In this review, we aim to describe the current studies conducted to better understand DSRCT biology and to explore the new therapeutic strategies under investigation in preclinical models and in early phase clinical trials.

Cutaneous non-epitheliotropic large T-cell lymphoma in an English Bulldog

Cutaneous lymphoma is histologically classified in epitheliotropic and non-epitheliotropic, the first showing higher incidence in dogs, and the second, in cats. Non-epitheliotropic lymphoma presents lymphocyte aggregates in the dermis and subcutaneous tissue, however cutaneous annexes are not infiltrated. It is usually more aggressive than epitheliotropic lymphomas. The aim of this study was to report a case of non-epitheliotropic lymphoma in a 9-year-old, female, English Bulldog presented with non-ulcerated skin nodules adhered to deep tissues. Microscopic and immunophenotypic features supported the diagnosis of non-epitheliotropic large T-cell lymphoma. Treatment was initiated with modification of the LOPP protocol, replacing procarbazine by dacarbazine (600 mg/m²) for up to six cycles, with a three-month survival. In the 11th week of treatment, after recurrent episodes of vomiting and diarrhea, abdominal ultrasound was performed and revealed an infiltrative mass in the stomachs greater curvature topography, showing an expansive and accentuated increase in one week, when euthanasia was elected.(AU)

Cutaneous non-epitheliotropic large T-cell lymphoma in an English Bulldog

Cutaneous lymphoma is histologically classified in epitheliotropic and non-epitheliotropic, the first showing higher incidence in dogs, and the second, in cats. Non-epitheliotropic lymphoma presents lymphocyte aggregates in the dermis and subcutaneous tissue, however cutaneous annexes are not infiltrated. It is usually more aggressive than epitheliotropic lymphomas. The aim of this study was to report a case of non-epitheliotropic lymphoma in a 9-year-old, female, English Bulldog presented with non-ulcerated skin nodules adhered to deep tissues. Microscopic and immunophenotypic features supported the diagnosis of non-epitheliotropic large T-cell lymphoma. Treatment was initiated with modification of the LOPP protocol, replacing procarbazine by dacarbazine (600 mg/m²) for up to six cycles, with a three-month survival. In the 11th week of treatment, after recurrent episodes of vomiting and diarrhea, abdominal ultrasound was performed and revealed an infiltrative mass in the stomach’s greater curvature topography, showing an expansive and accentuated increase in one week, when euthanasia was elected.

Histological classification and expression of markers of canine mast cell tumors.

BACKGROUND AND AIM: Mast cell tumors (MCTs) are malignant neoplasms that are common in dogs. Their biological behavior is variable and unpredictable. The aim of the present study was to analyze the histological classification and expression of markers of canine MCTs. MATERIALS AND METHODS: Thirty samples of canine MCTs were graded according to the histological classification methods of Patnaik and those of Kiupel. The expression of phosphoprotein 53 (p53) and c-kit proteins was quantified by immunohistochemistry using image processing software, ImageJ - a public domain computer program, developed at the National Institutes of Health. RESULTS: It was possible to determine the grade of 100% of the samples. According to Patnaik's classification, 20.00% of the samples were Grade 1, 43.30% were Grade 2, and 36.70% were Grade 3. According to Kiupel's classification, 56.67% of the samples were of high intensity and 43.33% were of low intensity. Grade 1 tumors had the highest expression of p53 and c-kit, and Grade 2 had the lowest expression. The results showed that it is necessary to perform both histological grading methods. The classification into high and low intensity may provide more consistent results than the three-level grading system. However, a smaller number of categories, although it facilitates the classification, may not be sufficient for the prognosis. CONCLUSION: Quantitative evaluation of p-53 and c-kit expression is a useful tool to increase the accuracy of the analysis and to aid in choosing the treatment method for canine MCTs. Histological grading should be combined with other diagnostic methods.

Tumor desmoplásico de célula pequeña y redonda paratesticular/testicular: reporte de caso y revisión de la literatura / Paratesticular/testicular desmoplastic round small cell malignant tumor: case report and literature review

Resumen El tumor desmoplásico de célula redonda y pequeña (TDCRP) es una patología neoplásica maligna agresiva y poco común. Afecta predominantemente a hombres entre la segunda y tercera década de la vida. Los pacientes que la padecen tienen un pronóstico pobre, con una supervivencia global a 5 años de hasta el 30%. Por lo general se presenta como una masa en la cavidad abdominal, frecuentemente multifocal. Para su tratamiento se recomienda un enfoque multimodal con cirugía, quimioterapia y radioterapia. Poco más de 20 casos de TDCRP a nivel testicular/paratesticular se han reportado en la literatura. A continuación, se presenta un caso ilustrativo en esta localización, se discute el caso y se realiza revisión de la literatura.

Abstract Desmoplastic small round cell tumor (DSRCT) is an aggressive and rare malignant neoplasm. It mainly affects young men in their twenties and thirties. Patients with it have a poor prognosis, with a 5-year survival rate of up to 30%. It generally presents as a mass in the abdominal cavity, often multifocal. A multimodal approach is recommended for its treatment, with surgery, chemotherapy, and radiotherapy. Just over 20 cases of testicular/paratesticular DSRCT have been reported in the literature. Below, we present an illustrative case in this location, we discuss the case and review the literature.

Desmoplastic small round cell tumor of the ovary: A case report with a new modality of treatment and review of the literature

Abstract Objective Desmoplastic small round cell tumor (DSRCT) is a rare intraabdominal neoplasm that grows along serosal surfaces and is primarily found in young men. To Keywords date, only 16 cases of ovarian DSRCT have been previously reported in women in the English literature, and no large population-based studies on this topic exist. Case Report We report the case of a 19-year-old virgo with unremarkable past medical history, initially presented with abdominal fullness. After being treated with the optimal treatment modality (primary and secondary surgical debulking, unique chemotherapy, protocol and adjuvant radiotherapy), the patient has remained without tumor disease for 40 months. Conclusion Although the best therapy for patients with DSRCT has yet to be determined, combining complete surgical resection, adjuvant chemotherapy, and radiotherapy is required to prolong survival and to achieve proper quality of life.

Tumor desmoplásico de células pequeñas y redondas. Presentación de caso y revisión de la literatura / Desmoplastic Small Round Cell Tumor. A Case Report and Literature Review

El tumor desmoplásico de células pequeñas y redondas (TDCPR) es una neoplasia maligna rara, con curso clínico agresivo y mortalidad elevada. Se presenta el caso de un hombre de 21 años de edad, quien consultó por dolor abdominal de intensidad moderada, irradiado al flanco derecho, fiebre y pérdida de peso. En tomografía abdominal con medio de contraste se documentó una gran masa intraperitoneal con áreas de necrosis central y extensión a la pelvis, además de lesiones hepáticas de aspecto neoplásico secundario. El diagnóstico se confirmó mediante biopsia percutánea guiada por ultrasonido, que mostró extensa infiltración por tumor maligno, constituido por células con núcleos vesiculosos de cromatina clara, citoplasma eosinófilo e inmunohistoquímica compatible con dicho tumor. En este artículo se hace una confrontación del caso con los hallazgos descritos en otras series publicadas en la literatura y una revisión clínica del tema.

Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm with an aggressive clinical course and high mortality. The case of a 21-year-old man is presented, who consulted for abdominal pain of moderate intensity radiating to the right flank, fever and weight loss. Contrast abdominal tomography was performed, documenting a large intraperitoneal mass with areas of central necrosis and extension to the pelvis, in addition to secondary neoplastic liver lesions. The diagnosis was confirmed by ultrasound-guided percutaneous biopsy, which reported extensive infiltration by malignant tumor, consisting of cells with vesicular nuclei of clear chromatin, eosinophilic cytoplasm and immunohistochemistry compatible with said tumor. This case report is compared with the findings described in other series published in the literature and a clinical review of the subject is made.

Multimodal treatment of an extremely rare desmoplastic small round cell tumor primary to the brachial plexus - A case report and review of literature.

BACKGROUND: Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive malignant neoplasm typically located in the abdomen or pelvis. Other possible locations are the chest, pleura, scrotum, and central nervous system. DSRCT originally arising from the brachial plexus (BP) is extremely rare, to the best of our knowledge, only two cases have been previously described in the English scientific literature. CASE DESCRIPTION: The authors present one new case of DSRCT arising from the left BP, the first in this location with rapid progression and in a female patient. We also highlight the importance of multimodal therapy, which included resection and both adjuvant radiation and chemotherapy. Macroscopic and microscopic characteristics of the lesion are detailed, as well as the patient's status at 56-month follow-up. CONCLUSION: For primary BP DSRCT, aggressive subtotal resection followed by radiation and chemotherapy can be satisfactory for disease control and for maintaining or improving the neurological status.

Ocorrência simultânea de hemangiossarcoma e mastocitoma de grau II em cão da raça Pitbull / Simultaneous occurrence of hemangiosarcoma and grade II mast cell tumor in a Pit Bull Terrier

Background: The incidence of cutaneous neoplasms in dogs is high and quite variable. Hemangiosarcoma (HSA) and mast celltumor (MCT) are commonly diagnosed neoplasms in isolation; however, reports of concomitant occurrence in a single patientare rare. HSA is a malignant mesenchymal neoplasm of endothelial origin; the spleen is the most commonly affected organ.MCT is a common neoplasm that may affect any region of the body, without predilection for sex, although some breeds haveshown higher incidence. This report describes a case of HSA and MCT in a Pit bull terrier.Case: A 5-year-old white male Pit bull was presented to the Small Animal Clinic of the Federal Rural University of Pernambucowith nodules in preputial region measuring 5.4 x 3.7 cm and an ulcerated nodule in the right lateral thoracic region measuring23.0 x 19.0 x 5.5 cm. The owner reported surgical excision of two previous nodules one year before the consultation, but neitherwere submitted for cytopathological or post-surgical histopathological examination. Two months after the procedure, the nodulesrecurred. Cytopathological examinations of preputial and lateral thoracic nodules were performed, with a suggestive diagnosisfor HSA and MCT, respectively. Due to the unfavorable prognosis and the weakness of the animal, euthanasia was elected.Necroscopic examination revealed an ideal body condition score (4/9), hypertrophy of right pre-scapular and axillary lymphnodes, red hepatization in the apical lobe of the right lung, with multiple, soft and pigmented nodules in the spleen, liver, pancreas and testis. Several tissue samples were collected, conditioned in 10% buffered formaldehyde solution, routinely processedfor histology, and stained with hematoxylin-eosin and toluidine blue. Microscopically, the lateral thoracic nodule consisted ofround cells in cordonal arrangement, with sparse basophilic and discretely granular cytoplasm...(AU)

Irinotecan and vincristine for the treatment of refractory desmoplastic small round cell tumor in a developing country: a case report.

INTRODUCTION: Desmoplastic small round cell tumor is an extremely rare and aggressive cancer that affects mainly adolescents and young adults. Despite multiple therapeutic strategies, most patients have resistant disease with very poor survival rates. CASE PRESENTATION: We present a case of a 10-year-old Caucasian boy with a desmoplastic small round cell tumor refractory to conventional treatment who exhibited a good response to alternative treatment. With use of irinotecan and vincristine in association with radiation therapy, a reduction of 96.9% of the dimensions of the target lesions compared with the initial image was observed. CONCLUSION: This chemotherapy regimen, in association with radiation therapy, demonstrated efficacy for refractory desmoplastic small round cell tumor in our patient, and it is cost-effective.

Ocorrência simultânea de hemangiossarcoma e mastocitoma de grau II em cão da raça Pitbull / Simultaneous occurrence of hemangiosarcoma and grade II mast cell tumor in a Pit Bull Terrier

Background: The incidence of cutaneous neoplasms in dogs is high and quite variable. Hemangiosarcoma (HSA) and mast celltumor (MCT) are commonly diagnosed neoplasms in isolation; however, reports of concomitant occurrence in a single patientare rare. HSA is a malignant mesenchymal neoplasm of endothelial origin; the spleen is the most commonly affected organ.MCT is a common neoplasm that may affect any region of the body, without predilection for sex, although some breeds haveshown higher incidence. This report describes a case of HSA and MCT in a Pit bull terrier.Case: A 5-year-old white male Pit bull was presented to the Small Animal Clinic of the Federal Rural University of Pernambucowith nodules in preputial region measuring 5.4 x 3.7 cm and an ulcerated nodule in the right lateral thoracic region measuring23.0 x 19.0 x 5.5 cm. The owner reported surgical excision of two previous nodules one year before the consultation, but neitherwere submitted for cytopathological or post-surgical histopathological examination. Two months after the procedure, the nodulesrecurred. Cytopathological examinations of preputial and lateral thoracic nodules were performed, with a suggestive diagnosisfor HSA and MCT, respectively. Due to the unfavorable prognosis and the weakness of the animal, euthanasia was elected.Necroscopic examination revealed an ideal body condition score (4/9), hypertrophy of right pre-scapular and axillary lymphnodes, red hepatization in the apical lobe of the right lung, with multiple, soft and pigmented nodules in the spleen, liver, pancreas and testis. Several tissue samples were collected, conditioned in 10% buffered formaldehyde solution, routinely processedfor histology, and stained with hematoxylin-eosin and toluidine blue. Microscopically, the lateral thoracic nodule consisted ofround cells in cordonal arrangement, with sparse basophilic and discretely granular cytoplasm...

A genomic case study of desmoplastic small round cell tumor: comprehensive analysis reveals insights into potential therapeutic targets and development of a monitoring tool for a rare and aggressive disease.

BACKGROUND: Genome-wide profiling of rare tumors is crucial for improvement of diagnosis, treatment, and, consequently, achieving better outcomes. Desmoplastic small round cell tumor (DSRCT) is a rare type of sarcoma arising from mesenchymal cells of abdominal peritoneum that usually develops in male adolescents and young adults. A specific translocation, t(11;22)(p13;q12), resulting in EWS and WT1 gene fusion is the only recurrent molecular hallmark and no other genetic factor has been associated to this aggressive tumor. Here, we present a comprehensive genomic profiling of one DSRCT affecting a 26-year-old male, who achieved an excellent outcome. METHODS: We investigated somatic and germline variants through whole-exome sequencing using a family based approach and, by array CGH, we explored the occurrence of genomic imbalances. Additionally, we performed mate-paired whole-genome sequencing for defining the specific breakpoint of the EWS-WT1 translocation, allowing us to develop a personalized tumor marker for monitoring the patient by liquid biopsy. RESULTS: We identified genetic variants leading to protein alterations including 12 somatic and 14 germline events (11 germline compound heterozygous mutations and 3 rare homozygous polymorphisms) affecting genes predominantly involved in mesenchymal cell differentiation pathways. Regarding copy number alterations (CNA) few events were detected, mainly restricted to gains in chromosomes 5 and 18 and losses at 11p, 13q, and 22q. The deletions at 11p and 22q indicated the presence of the classic translocation, t(11;22)(p13;q12). In addition, the mapping of the specific genomic breakpoint of the EWS-WT1 gene fusion allowed the design of a personalized biomarker for assessing circulating tumor DNA (ctDNA) in plasma during patient follow-up. This biomarker has been used in four post-treatment blood samples, 3 years after surgery, and no trace of EWS-WT1 gene fusion was detected, in accordance with imaging tests showing no evidence of disease and with the good general health status of the patient. CONCLUSIONS: Overall, our findings revealed genes with potential to be associated with risk assessment and tumorigenesis of this rare type of sarcoma. Additionally, we established a liquid biopsy approach for monitoring patient follow-up based on genomic information that can be similarly adopted for patients diagnosed with a rare tumor.

Requirement for novel surgical and clinical protocols for the treatment of desmoplastic small round cell tumor: A report of two cases and a review of the literature.

Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive neoplasm that was initially described in 1989. DSRCT predominantly affects young men and typically occurs in the intra-abdominal area. The present study describes the cases of two patients with DSRCT. The first patient was a 23-year-old male who presented with abdominal pain in the right flank, coupled with difficulty urinating and bowel dysfunction. The second patient was 12-year-old female who presented with abdominal pain, emesis and loss of appetite. A computed tomography scan of the abdomen revealed the presence of an extensive pelvic mass in each patient, however, a visceral origin was not clearly identifiable in the first patient. In the second patient, a large soft-tissue tumor was located posterior to the pancreatic tail and the stomach, with no anatomical line visible between the stomach and splenic vein. Ultrasound-guided biopsy in the first patient and videolaparoscopy in the second patient followed by immunohistochemical analysis clarified the presence of a malignant neoplasm composed of small, blue, round cells. Due to right ureter involvement and hydronephrosis in the first patient, a treatment strategy of surgical debulking of the tumor was selected. The surgical procedure involved en bloc resection of the lesion associated with a pelvic peritonectomy, followed by post-operative radiotherapy. However, the second patient exhibited extensive disease, therefore, a chemotherapeutic protocol of vincristine, doxorubicin and cyclophosphamide, as well as radiation therapy, was scheduled. Disease relapse was observed in the abdominal cavity of the first patient after one year, while the second patient remains asymptomatic. Following analysis of present two cases, it was concluded that aggressive treatment regimens may induce tumor regression. However, relapse of the disease is frequent and long-term survival is rare with the currently available therapeutic strategies.