scholarly journals Succinate dehydrogenase deficient gastrointestinal stromal tumor in a three month old boy with a fatal clinical course: a case report and review of literature

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Bei-Bei Lv ◽  
Jia-Mei Li ◽  
Zhi-Gang Yao ◽  
Xian-Kui Cheng ◽  
Fu-Xin Ren ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Tumor Cells ◽  
Mutational Analysis ◽  
Tumor Type ◽  
Review Of Literature ◽  
Wild Type ◽  
Case Presentation ◽  
Colon Wall ◽  
Regional Lymphadenectomy ◽  
Segmental Bowel Resection

Abstract Background Succinate dehydrogenase deficient gastrointestinal stromal tumors (SDH-deficient GISTs), which lack KIT or PDGFRA mutations demonstrate unique clinical and pathological features, and they respond poorly to standard targeted therapy. We herein present a novel case of SDH-deficient GIST in a three-month-old infant’s colon mesentery, and he is the youngest patientto date. Case presentation The infantpresented with complaints of blood in the stool. CT showed a 6.3 × 4.6 cm mass in the left lower retroperitoneal. Complete resection of tumor and segmental bowel resection was performed without regional lymphadenectomy. Histologically, tumor cells were distinctive in their multinodular colon wall involvement with interspersed tracts of colon wall smooth muscle. The tumor was composed mainly of epithelioid cells. Immunohistochemically, the tumor cells were positive for Vim, CD117, PDGFR, while negative for SDHB. Mutational analysis showed a synonymous mutation for SDHB and wild-type for KIT and PDGFRA. Two months after surgery, metastases were found and Imatinib was administered. Unfortunately, the disease continued to progress, and the infant died 5 months after surgery. Conclusions SDH-deficient GISTs comprise a subgroup of a relatively rare tumor type and show a number of clinically and biologically unique features, especially for infants. It is of great importance to developing new therapeutic targets and novel specific drugs.

scholarly journals Succinate dehydrogenase deficient gastrointestinal stromal tumor in a three month old boy with a fatal clinical course: A case report and review of literature

2021 ◽  
Author(s):  
Bei-bei Lv ◽  
Jia-Mei Li ◽  
Zhi-Gang Yao ◽  
Xian-Kui Cheng ◽  
Fu-Xin Ren ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Tumor Cells ◽  
Mutational Analysis ◽  
Tumor Type ◽  
Review Of Literature ◽  
Wild Type ◽  
Case Presentation ◽  
Colon Wall ◽  
Regional Lymphadenectomy ◽  
Segmental Bowel Resection

Abstract Background: Succinate dehydrogenase deficient gastrointestinal stromal tumors (SDH-deficient GISTs), which lack KIT or PDGFRA mutations demonstrate unique clinical and pathological features, and they respond poorly to standard targeted therapy. We herein present a novel case of SDH-deficient GIST in a three-month-old infant’s colon mesentery, and he is the youngest patient to date .Case presentation: The infant presented with complaints of blood in the stool. CT showed a 6.3×4.6 cm mass in the left lower retroperitoneal. Complete resection of tumor and segmental bowel resection was performed without regional lymphadenectomy. Histologically, tumor cells were distinctive in their multinodular colon wall involvement with interspersed tracts of colon wall smooth muscle. The tumor was composed mainly of epithelioid cells. Immunohistochemically, the tumor cells were positive for Vim, CD117, PDGFR, while negative for SDHB. Mutational analysis showed a synonymous mutation for SDHB and wild-type for KIT and PDGFRA. Two months after surgery, metastases were found and Imatinib was administered. Unfortunately, the disease continued to progress, and the infant died 5 months after surgery.Conclusions: SDH-deficient GISTs comprise a subgroup of a relatively rare tumor type and show a number of clinically and biologically unique features, especially for infants. It is of great importance to developing new therapeutic targets and novel specific drugs.

scholarly journals Succinate Dehydrogenase Deficient Gastrointestinal Stromal Tumor in a Three Month Old Boy With a Fatal Clinical Course: A Case Report and Review of Literature

2020 ◽  
Author(s):  
Bei-bei lv ◽  
Jia-Mei Li ◽  
Zhi-Gang Yao ◽  
Xian-Kui Cheng ◽  
Fu-Xin Ren ◽  
...  
Keyword(s):  
Succinate Dehydrogenase ◽  
Bowel Resection ◽  
Mutational Analysis ◽  
Tumor Type ◽  
Review Of Literature ◽  
Wild Type ◽  
Case Presentation ◽  
Colon Wall ◽  
Regional Lymphadenectomy ◽  
Segmental Bowel Resection

Abstract Background: Succinate dehydrogenase deficient gastrointestinal stromal tumors (SDH-deficient GISTs) which lack KIT or PDGFRA mutations demonstrate unique clinical and pathological features, and respond poorly to standard targeted therapy. We herein present a novel case of SDH-deficient GIST in a three-month-old boy in colon mesentery which is the youngest patient until now. Case presentation: The baby presented with complaints of blood in the stool. CT showed a 6.3×4.6 cm mass in the left lower retroperitoneal. Complete resection of tumor and segmental bowel resection was performed without regional lymphadenectomy. Histologically, tumors are distinctive in their multinodular colon wall involvement with interspersed tracts of colon wall smooth muscle. The tumor was composed mainly of epithelioid cells. Immunohistochemically, the tumor cells were positive for Vim, CD117, PDGFR, while negative for SDHB. Mutational analysis showed a synonymous mutation for SDHB and wild-type for KIT and PDGFRA. Two months after surgery, metastases were found and Imatinib was administered. Unfortunately, the disease continued to progress, the baby died 5 months after surgery. Conclusions: SDH-deficient GISTs comprise a subgroup of a relatively rare tumor type and show a number of clinically and biologically unique features, especially for infants. It is of great importance to developing new therapeutic targets and novel specific drugs.

scholarly journals Primary epithelioid rhabdomyosarcoma of the stomach: a case report and review of literature

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Yangkun Wang ◽  
Pei Guo ◽  
Zhishang Zhang ◽  
Runde Jiang ◽  
Zuguo Li
Keyword(s):  
Tumor Cells ◽  
Unusual Case ◽  
Histopathological Examination ◽  
Gastroesophageal Junction ◽  
Rare Tumor ◽  
Review Of Literature ◽  
Ki 67 ◽  
Case Presentation ◽  
Cytoplasmic Content ◽  
Mitotic Figures

Abstract Background Epithelioid rhabdomyosarcoma is a rare tumor that generally occurs in the bladder, the parotid gland, or the skin of the neck. We describe an unusual case of primary epithelioid rhabdomyosarcoma of the stomach and review the literature. Case presentation A 64-year-old woman presented with a lesion at the gastroesophageal junction. Histopathological examination showed irregularly sized round cells with low cytoplasmic content and eccentric nuclei. Mitotic figures were present. Fibrovascular septa and areas of necrosis were observed between tumor cells. Tumor cells were strongly positive for MyoD1, desmin, and myogenin, and weakly positive for actin, CD56, and PGP9.5. The ki-67 index was ≥90%. Conclusions Primary epithelioid rhabdomyosarcoma of the stomach is extremely rare. Better awareness of this entity is necessary for early diagnosis and treatment.

scholarly journals Similarities and Differences between Clear Cell Tubulo-Papillary and Conventional Clear Cell Renal Cell Carcinoma: A Comparative Phenotypical and Mutational Analysis

Diagnostics ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 123
Author(s):  
Francesca Giunchi ◽  
Tania Franceschini ◽  
Elisa Gruppioni ◽  
Annalisa Altimari ◽  
Elisa Capizzi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Differential Diagnosis ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Mutational Analysis ◽  
Papillary Renal Cell Carcinoma ◽  
Tumor Type ◽  
Wild Type ◽  
Cell Renal Cell Carcinoma

Background: Clear cell tubulo-papillary renal cell carcinoma (cctpRCC) is characterized by clear cell morphology, but differs from conventional clear cell carcinoma (ccRCC) for its indolent clinical behavior and genetic background. The differential diagnosis between the two is based on histology and immunohistochemistry (IHC). Methods: We performed a comparative case-control histological, IHC, and genetic analysis by next generation sequencing (NGS), to point out the differences in 10 cases of cctpRCC, and six controls of ccRCC with low stage and grade. Results: All 16 cases showed the IHC profile with cytokeratin 7, racemase, and carbonic anhydrase IX expected for the histological features of each tumor type. By contrast, the NGS mutation analysis that covered 207 amplicons of 50 oncogenes or tumor suppressor genes provided conflicting results. Among the 10 cctpRCC cases, eight (80%) were wild type for all of the genes in the panel, while two (20%) harbored VHL mutations typical of ccRCC. Three of the six (50%) ccRCC control cases showed expected VHL mutations; two (33%) harbored pathogenic mutations in the p53 or the CKIT genes; and one (16%) was wild type. Conclusion: We can assume that histology and ICH are not sufficient for a definitive diagnosis of cctpRCC or ccRCC. Although with a panel covering 50 genes, we found that 80% of cctpRCC were genetically silent; thus, suggesting an indolent biology of these tumors. The differential diagnosis between ccptRCC and ccRCC for the choice of the best therapeutic strategy likely requires the comprehensive evaluation of histology, IHC, and at least VHL mutations.

scholarly journals Successful laparoscopic resection of ovarian abscess caused by Staphylococcus aureus in a 13-year-old girl: a case report and review of literature

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tsuyoshi Murata ◽  
Yuta Endo ◽  
Shigenori Furukawa ◽  
Atsushi Ono ◽  
Yuichiroh Kiko ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Adolescent Girls ◽  
Laparoscopic Resection ◽  
Sexually Active ◽  
Fallopian Tubes ◽  
Review Of Literature ◽  
Case Presentation ◽  
Intact Uterus ◽  
Ovarian Abscess ◽  
Tomography Scan

Abstract Background Ovarian abscesses, which occur mostly in sexually active women via recurrent salpingitis, occur rarely in virginal adolescent girls. Here, we present a case of an ovarian abscess in a virginal adolescent girl who was diagnosed and treated by laparoscopy. Case presentation A 13-year-old healthy girl presented with fever lasting for a month without abdominal pain. Computed tomography scan and magnetic resonance imaging indicated a right ovarian abscess. Laparoscopic surgery revealed a right ovarian abscess with intact uterus and fallopian tubes. The abscess was caused by Staphylococcus aureus. The patient recovered completely after excision of the abscess, followed by antibiotic treatment. Conclusions Ovarian abscess may occur in virginal adolescent girls; Staphylococcus aureus, an uncommon species causing ovarian abscess, may cause the infection.

282 Pan-tumor analysis of the association between PD-L1 combined positive score and response to pembrolizumab monotherapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A308-A308
Author(s):  
Lingkang Huang ◽  
Jared Lunceford ◽  
Junshui Ma ◽  
Kenneth Emancipator
Keyword(s):  
Tumor Cells ◽  
Immune Cells ◽  
Roc Analysis ◽  
Standard Of Care ◽  
Tumor Type ◽  
Operating Characteristics ◽  
Positive Score ◽  
Combined Positive Score ◽  
Line Of Therapy ◽  
Tumor Types

BackgroundPD-L1 is expressed on both tumor and immune cells; however, the mechanism by which PD-L1 modulates the adaptive immune response on tumor versus immune cells may differ. Additionally, the prevalence of PD-L1 expression and the partitioning between tumor and immune compartments varies by tumor type. While PD-L1 expression on tumor or immune cells can be scored separately, the PD-L1 combined positive score (CPS) captures both tumor and immune cell expression in one aggregate score. We performed a retrospective, exploratory analysis of the effectiveness of CPS as an enrichment biomarker across several studies of pembrolizumab monotherapy in patients with multiple tumor types.MethodsPD-L1 expression was assessed using PD-L1 IHC 22C3 pharmDx. Expression was measured using CPS (defined as the number of PD-L1–staining cells [tumor cells, lymphocytes, macrophages] divided by the total number of tumor cells, multiplied by 100) in tumor samples from single-arm (KEYNOTE-052 [UC], KEYNOTE-059 cohort 1 [G/GEJ], KEYNOTE-086 [TNBC], KEYNOTE-158 [cervical; SCLC], KEYNOTE-180 [EC], KEYNOTE-224 [HCC], KEYNOTE-427 [RCC]) and randomized (KEYNOTE-040 [HNSCC], KEYNOTE-045 [UC], KEYNOTE-061 [G/GEJ], KEYNOTE-119 [TNBC], KEYNOTE-240 [HCC]) pembrolizumab studies. Data were pooled across tumor types for pembrolizumab and for standard-of-care (in controlled studies), and then estimates of response rate, prevalence, and receiver operating characteristics (ROC) analysis were performed over various CPS cutpoints. CPS distribution by response, tumor type, and line of therapy were also assessed.ResultsThere were 3769 treated patients with available PD-L1 CPS (pembrolizumab, n=2678; standard-of-care, n=1091). The area under the ROC curve for ORR was 0.63 (95% CI, 0.61–0.66) for pembrolizumab and 0.48 (95% CI, 0.43–0.53) for standard-of-care when a positive association was evaluated between CPS and ORR (figure 1); individual cutpoints of 1, 10, 20, and 50 were examined (table 1). Figure 2 shows a boxplot of CPS distribution for response in pembrolizumab-treated patients.Abstract 282 Table 1Response Rates and Sensitivity at Individual CPS Cutpoints for Pembrolizumab-Treated PatientsAbstract 282 Figure 1ROC analysis of PD-L1 CPS for pembrolizumab versus standard-of-care therapyAbstract 282 Figure 2Boxplot of PD-L1 CPS distribution for responders versus nonresponders in pembrolizumab-treated patients by tumor type and line of therapy in order of descending median CPSConclusionsThis retrospective, exploratory pan-tumor analysis demonstrates that CPS is an effective scoring method for measuring PD-L1 expression and can be used as a predictive biomarker to identify patients likely to respond to pembrolizumab monotherapy. CPS demonstrated enrichment of response to pembrolizumab monotherapy across most, but not all, tumor types, including some tumor types for which efficacy favors pembrolizumab regardless of PD-L1 expression, and for which a companion diagnostic is therefore not needed. In the randomized studies, CPS did not show a consistent association with ORR for standard-of-care therapy.

scholarly journals Semi-Synthesis of Small Molecules of Aminocarbazoles: Tumor Growth Inhibition and Potential Impact on p53

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1637
Author(s):  
Solida Long ◽  
Joana B. Loureiro ◽  
Carla Carvalho ◽  
Luís Gales ◽  
Lucília Saraiva ◽  
...  
Keyword(s):  
Growth Inhibition ◽  
Small Molecules ◽  
Tumor Cells ◽  
Mutant P53 ◽  
Wild Type ◽  
Naturally Occurring ◽  
Growth Inhibitory ◽  
Growth Inhibitory Activity ◽  
Amino Derivatives ◽  
Carbazole Alkaloids

The tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. Small molecules that bind and stabilize those mutants may represent effective anticancer drugs. Herein, we report the tumor cell growth inhibitory activity of carbazole alkaloids and amino derivatives, as well as their potential activation of p53. Twelve aminocarbazole alkaloids were semi-synthesized from heptaphylline (1), 7-methoxy heptaphylline (2), and 7-methoxymukonal (3), isolated from Clausena harmandiana, using a reductive amination protocol. Naturally-occurring carbazoles 1–3 and their amino derivatives were evaluated for their potential effect on wild-type and mutant p53 activity using a yeast screening assay and on human tumor cell lines. Naturally-occurring carbazoles 1–3 showed the most potent growth inhibitory effects on wild-type p53-expressing cells, being heptaphylline (1) the most promising in all the investigated cell lines. However, compound 1 also showed growth inhibition against non-tumor cells. Conversely, semi-synthetic aminocarbazole 1d showed an interesting growth inhibitory activity in tumor cells expressing both wild-type and mutant p53, exhibiting low growth inhibition on non-tumor cells. The yeast assay showed a potential reactivation of mutant p53 by heptaphylline derivatives, including compound 1d. The results obtained indicate that carbazole alkaloids may represent a promising starting point to search for new mutp53-reactivating agents with promising applications in cancer therapy.

Sign in / Sign up

Export Citation Format

Share Document