Molecular Targeted Therapies: Time for a Paradigm Shift in Medulloblastoma Treatment?

Medulloblastoma is a rare malignancy of the posterior cranial fossa. Although until now considered a single disease, according to the current WHO classification, it is a heterogeneous tumor that comprises multiple molecularly defined subgroups, with distinct gene expression profiles, pathogenetic driver alterations, clinical behaviors and age at onset. Adult medulloblastoma, in particular, is considered a rarer “orphan” entity in neuro-oncology practice because while treatments have progressively evolved for the pediatric population, no practice-changing prospective, randomized clinical trials have been performed in adults. In this scenario, the toughest challenge is to transfer the advances in cancer genomics into new molecularly targeted therapeutics, to improve the prognosis of this neoplasm and the treatment-related toxicities. Herein, we focus on the recent advances in targeted therapy of medulloblastoma based on the new and deeper knowledge of disease biology.

MANAGEMENT OF ADRENO CORTICAL CARCINOMA: CASE REPORT

Objective: Adreno cortical carcinoma (ACC) is a rare malignancy. Currently, surgical resection offers the best chance of cure with localized tumor. Multimodal therapy including systemic chemotherapy and radiation therapy are often required for locally advanced and metastatic disease aims to decrease these high recurrence rates. Case(s) presentation: A 42-year-old male patient was referred from internist due to mass in left adrenal. Solid mass with calcification on left adrenal gland within size 9 x 11.8 x 11.5 cm was found in MSCT. We performed complete surgical resection (adrenalectomy), and results from pathology anatomy was ACC functional T2N1M0 (stage 3). The patient was planned eight times chemotherapy with etoposide and carboplatin, but he decided to stop the treatment after six times due to no constitutional complaint. We found no residual mass on follow up six months after operation and patient demonstrated a good clinical outcome after one year. Discussion: We perform open adrenalectomy and after surgery mitotane plus etoposide, cisplatin, doxorubicin (EDP) administered as first-line therapy but we only did chemotherapy with etoposide and carboplatin because mitotane was not covered by patient insurance. We chose to not perform radiation therapy due to lesser benefit of adjuvant radiotherapy as evidenced by many studies in term of recurrence-free survival and overall survival. Conclusion: In our case, adreno cortical carcinoma treated with open adrenalectomy combined with 6 times chemotherapy used etoposide and carboplatin demonstrated a good clinical outcome after 1 year.

New Era for Malignant Pleural Mesothelioma: Updates on Therapeutic Options

Malignant pleural mesothelioma (MPM) is a rare malignancy with few treatment options. Recent advances have led to US Food and Drug Administration approvals and changes in the standard of care with a novel biomedical device approved for use with platinum-pemetrexed, and also for immunotherapy agents to be included as a frontline treatment option in unresectable disease. Although predictive biomarkers for systemic therapy are not currently in use in clinical practice, it is essential to correctly identify the MPM histology to determine an optimal treatment plan. Patients with nonepithelioid MPM may have a greater magnitude of benefit to dual immunotherapy checkpoint inhibitors and this regimen should be preferred in the frontline setting for these patients. However, all patients with MPM can derive benefit from immunotherapy treatments, and these agents should ultimately be used at some point during their treatment journey. There are ongoing studies in the frontline unresectable setting that may further define the frontline therapy space, but a critical area of research will need to focus on the immunotherapy refractory population. This review article will describe the new developments in the areas of biology with genomics and chromothripsis, and also focus on updates in treatment strategies in radiology, surgery, radiation, and medical oncology with cellular therapies. These recent innovations are generating momentum to find better therapies for this disease.

Circulating Cell-Free DNA-Based Comprehensive Molecular Analysis of Biliary Tract Cancers Using Next-Generation Sequencing

Biliary tract cancer (BTC) is a rare malignancy with a long disease course and an overall poor prognosis. Despite multiple chemotherapy agents, there is no defined second-line treatment opportunity for advanced BTCs. In the era of precision oncology, NGS plays an important role in identifying mutations that may predict the molecular pathomechanism and manage the BTC therapy. The peripheral blood liquid biopsy (LB) of cancer patients represents variable amounts of cell-free DNA (cfDNA) released from tumor foci of any anatomical location. Our study aimed to identify somatic mutations and tumor variant burden (TVB) in cell-free and matched tumor DNA. We found a positive correlation between the estimated tumor volume and cfDNA yield (r = 0.9326, p < 0.0001). Comparing tissue and LB results, similar TVB was observed. SNVs were proven in 84% of the cases, while in two cases, only the LB sample was informative for molecular analysis. The most important aberrations in BTCs, such as FGFR2, IDH1, IDH2, KRAS, and TP53, could be detected in matched LB samples. Our prospective study demonstrates a minimally invasive testing approach to identify molecular genetic alterations in cholangiocarcinoma and gallbladder cancers. Clinical applications of cfDNA reflect by capturing the outstanding spatial tumor heterogeneity and guarantee novel aspects for the precision oncology treatment.

Sebaceous Carcinoma of the Vulva: An Unexpected Diagnosis and Literature Review

Sebaceous carcinoma of the vulva is a rare malignancy of the sebaceous glands, with potentially aggressive behaviour, that is usually found in the peri-ocular area. Nonetheless, there are sebaceous glands in the vulva and this diagnosis is especially rare, with only ten cases described in the literature. We report a case of 78-year-old female patient who presented with vulvar pruritus, previously treated with topical steroid and antifungal treatments, without improvement. The vulvar examination showed a visible yellow papule, 12 x 10 mm on the right major labia, which was biopsied and the microscopic examination revealed an invasive sebaceous carcinoma of the vulva, with an in situ component. We performed an uneventful excisional biopsy, followed by a subsequent margin widening. Three months after the diagnosis, she presented with the first recurrence. Two and half years after the diagnosis, she recurred with a larger lesion (13 mm) in the upper half of small right lip, more than 10 mm away from the midline. In a multidisciplinary meeting it was decided that the patient should undergo partial right vulvectomy with homolateral inguino-femoral sentinel node biopsy (one negative node). There was no evidence of recurrence one-year post-surgery.

Pitfalls and progress in adrenocortical carcinoma diagnosis: the utility of a multidisciplinary approach, immunohistochemistry and genomics

Summary Adrenocortical carcinoma is a rare disease with poor prognosis whose clinical heterogeneity can at times present a challenge to accurate and timely diagnosis. We present the case of a patient who presented with extensive pulmonary lesions, mediastinal and hilar lymphadenopathy and an adrenal mass in whom the oncological diagnosis was initially uncertain. Through the use of immunohistochemistry, biochemistry and genomic testing, an accurate diagnosis of adrenocortical carcinoma was ultimately made which resulted in more directed treatment being administered. The use of multidisciplinary input and genomics to aid in diagnosis and prognosis of adrenocortical carcinoma is discussed. Learning points Adrenocortical carcinomas can present a diagnostic challenge to clinicians given it is a rare malignancy with significant clinical heterogeneity. Specialist multidisciplinary team input is vital in the diagnosis and management of adrenocortical carcinomas. Hormonal testing is recommended in the diagnostic workup of adrenal masses, even in the absence of overt clinical signs/symptoms of hormone excess. Immunostaining for the highly sensitive and specific steroidogenic factor-1 is vital for accurate diagnosis. Genomics can provide prognostic utility in management of adrenocortical carcinoma.

Clinical benefit of R-CHOP without splenectomy in stage I primary splenic diffuse large B-cell lymphoma

Primary splenic diffuse large B-cell lymphoma (PS-DLBCL) is a relatively rare malignancy, and there are no optimal approaches for diagnosis and management. There are less invasive splenic biopsies that effectively obviate diagnostic and elective splenectomies. We report a man in his 50s with 2-day history of pain in the abdomen and who was found to have a splenic mass on PET-CT. A CT-guided core needle splenic biopsy confirmed the diagnosis of PS-DLBCL. He was managed with six cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) alone, without splenectomy. The patient attained complete remission, and he is disease free at 6 years of follow-up.

A Rare Case of Pulmonary Carcinosarcoma with Unusual Presentation: A Diagnostic Dilemma

Pulmonary carcinosarcoma is a rare malignancy of the lung and has poor prognosis than non-small cell lung cancer. Effective treatment has not been developed for non-resect able advanced stage. We report a case in a 51-year-old female who presented with a right sided massive pleural effusion. Pleural biopsy tissue histology and immunohistochemistry revealed carcinosarcoma.

Ung thư biểu mô tế bào thận có đột biến TFE3/Xp11.2 báo cáo một trường hợp ở trẻ em và đối chiếu y văn

TÓM TẮT Ung thư biểu mô tế bào thận (UTBM) - Renal cell carcinoma là khối u ác tính hiếm gặp, chỉ chiếm 2 - 6% các khối u thận ác tính ở trẻ em. UTBM tế bào thận có đột biến TFE3 trên nhiễm sắc thể Xp11.2 (TFE3/ Xp11.2) là một dưới nhóm của UTBM tế bào thận, thường có tiên lượng nặng hơn các nhóm khác của UTBM tế bào thận. Chúng tôi thông báo một trẻ 10 tuổi vào viện vì đau bụng và phát hiện khối u thận trái. Sau khi phẫu thuật cắt u được làm xét nghiệm mô bệnh học, nhuộm hóa mô miễn dịch TFE3(+), CD10(+), CK7(-) chẩn đoán: UTBM tế bào thận có đột biến TFE3/Xp11.2. Bệnh nhân ổn định, ra viện sau 2 tuần. Tái khám sau hai tháng không phát hiện u tái phát hay di căn. ABSTRACT RENAL CELL CARCINOMA ASSOCIATED WITH XP11.2 TRANSLOCATION FACTORE3 GENE FUSION: A CHILD CASE REPORT AND LITERATURE REVIEW Renal cell carcinoma is a rare malignancy, accounting for only 2 - 6% of renal malignancies in children. Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion is a subgroup of renal cell carcinoma, often with a more severe prognosis than other groups of renal cell carcinoma. We report on a 10 - year - old child was admitted to the hospital because of abdominal painand a left kidney tumor. After tumor resection, histopathological examination, immunohistochemical staining was positive for TFE3, CD10, negative for CK7, diagnosis renal cell carcinoma associated with Xp11.2 translocation factor E3 gene fusion. Two weeks after surgery, the patient was stable and discharged from the hospital. Re - examination after two months did not detect tumor recurrence or metastasis. Key word: Renal cell carcinoma, TFE3, Xp11.2 translocation.

Case Report: Exceptional Response to Nivolumab Plus Ipilimumab in a Young Woman With TFE3-SFPQ Fusion Translocation-Associated Renal Cell Carcinoma

Translocation-associated renal cell carcinoma (tRCC) is a rare, aggressive malignancy that primarily affects children and young adults. There is no clear consensus on the most effective treatment for tRCC and there are no biomarkers of response to treatments in these patients. We present a case of a 23 year-old female with metastatic tRCC to the lungs who was started on treatment with nivolumab and ipilimumab. She had a complete radiographic response to treatment and has been progression-free for over 18 months. Immunofluorescence imaging performed on the baseline primary tumor sample showed significant intratumoral immune infiltration. Importantly, these cells are present in niches characterized by TCF1+ CD8+ T cells. Histopathologic investigation showed the presence of lymphocytes in the fibrovascular septae and foci of lymphovascular invasion. Furthermore, lymphovascular invasion and intratumor niches with TCF1+ CD8+ T cells may predict a favorable response to treatment with nivolumab and ipilimumab. These findings have significant clinical relevance given that immune checkpoint inhibitors are approved for several malignancies and predictive biomarkers for response to treatment are lacking. Importantly, the identification of these TCF1+ CD8+ T cells may guide treatment for patients with tRCC, which is a rare malignancy without a consensus first-line treatment option.