Ewing's sarcoma in adolescents and adults - 10-year experience from a tertiary cancer center in India.

BACKGROUND: Ewing's sarcoma (EWS) is an aggressive small round cell tumor, affecting bone and soft tissues and is mostly seen in childhood and second decade of life. EWS accounts for 10-12% of bone tumors in more than 15 years age group and is even rarer after 40 years of age. MATERIALS AND METHODS: This retrospective analysis was conducted among patients aged more than 15 years with histologically proven EWS. RESULTS: Among 240 cases of EWS treated at our center during 2001-2010, 130 (54%) were more than 15 years of age. The median age was 20 years with a male: female ratio of 2.4:1. Ninety percent had skeletal EWS, 10% had extra skeletal EWS, and 37% patients were metastatic at presentation. Eighty-two received curative treatment with chemotherapy (vincristine, doxorubicin, cyclophosphamide, ifosfamide, etoposide (VAC/IE)) along with local treatment, radiotherapy (RT) in 61, surgery alone in seven, and RT plus surgery in 14. Two- and 5-year overall survival (OS) was 43.3% and 25.5%, respectively, for the entire series. The OS for the non-metastatic group was 63.2% at 2 years and 36.5% at 5 years, and the progression free survival was 53.7% at 2 years and 37.8% at 5 years. High lactate dehydrogenase was found to be a significant poor prognostic factor (P = 0.001). Median OS for localized central EWS was 49.2 months and that for peripheral EWS was 24 months. Patients more than 20 years of age with non-metastatic disease had better OS compared to those with 15-20 years of age. CONCLUSION: Treatment of EWS requires a multidisciplinary approach with radical surgery and/or radiation to control local disease and multiagent chemotherapy to control systemic disease. Long-term follow-up is essential because of disease relapse and treatment-related complications.

Angiosarcoma of the head and neck: A clinicopathologic study with special emphasis on diagnostic pitfalls.

BACKGROUND AND AIMS: Angiosarcoma (AS) is a rare malignant vascular tumor that phenotypically and functionally recapitulate normal endothelium. They constitute approximately 2-4% of soft tissue sarcomas. We present 36 cases of head and neck AS diagnosed for 11 years at a tertiary care hospital in South India to analyze the clinical, pathological, and immunophenotypic profiles with special emphasis on their differential diagnoses and diagnostic pitfalls. MATERIALS AND METHODS: Head and neck AS diagnosed from January 2006 to December 2017 were included. Clinical characteristics, treatment received, and follow-up data were obtained from electronic medical records. Hematoxylin and eosin (H&E)-stained slides and immunohistochemistry (IHC) slides were reviewed, and the histomorphological features, immunohistochemical staining, and their utility in resolving differential diagnosis were assessed. RESULTS: Twenty-two females and 14 males were diagnosed with head and neck AS in the study period. Histomorphological patterns observed were mixed vasoformative and solid ( n = 22), pure vasoformative ( n = 13), and pure solid ( n = 1). Neoplastic cells showed epithelioid, spindly, signet cell-like, clear cell, and rhabdoid morphology. CD31 was positive in 100% of cases, and CD34 was positive in 40% of cases. Differential diagnoses included melanoma, rhabdomyosarcoma, and large-cell lymphoma. Surgery, radiotherapy, and chemotherapy were the treatment modalities used. Twelve patients developed local recurrence, and 12 patients developed metastasis on follow-up. Twenty-five patients died of disease, on an average of 24 months after diagnosis. CONCLUSION: Head and neck AS pose a significant diagnostic challenge due to their broad morphologic spectrum. Proper clinicopathologic correlation is necessary to avoid misdiagnosis.

Castleman disease: Experience from a single institution.

Castleman disease (CD) describes a group of rare heterogeneous lymphoproliferative disorders characterized by enlarged hyperplastic lymph nodes. It is classified into unicentric CD (UCD) and multicentric CD (MCD). The present retrospective study examined the data of 11 patients with CD diagnosed and treated at a tertiary cancer center from 2017 to 2022. The median age of the study group was 41 years (range, 24 to 68 years). There were 8 males and 3 females. In total, 7 patients were diagnosed with UCD and 4 patients with MCD. The hyaline-vascular variant was the most common histology in both UCD and MCD. Among the 7 patients with UCD, 5 patients underwent excision, 1 patient underwent debulking followed by radiotherapy and 1 patient received single agent rituximab. Of the patients with UCD, 6 had a complete response (CR) and 1 patient had a partial response (PR). All 4 patients with MCD received systemic treatment, which included single agent rituximab (2 patients), rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone (RCHOP) (1 patient) and CHOP (1 patient). Among the patients with MCD, 1 patient attained a CR, 2 patients had a PR and 1 patient succumbed. The 3-year survival rate for the study population was 91%. In summary, CD is a rare disease occurring in immunodeficient patients. UCD is more common and is associated with better outcomes. Surgery is the mainstay of management in UCD whereas MCD requires combination chemotherapy.

Acute myeloid leukemia patients with variant or unusual translocations involving chromosomes 8 and 21 - A comprehensive cytogenetic profiling of three cases with review of literature.

Background: t(8;21)(q22;q22) is the most frequent recurrent translocation in acute myeloid leukemia (AML) resulting in an in-frame fusion of RUNX1/RUNX1T1 that regulates various genes involved in the signaling pathways. This leukemogenic alteration is usually associated with a favorable clinical outcome. Variants of t(8;21) can be formed involving a third or fourth chromosome in ~3-4% of t(8;21)-AML. Due to the rarity of variant t(8;21), its clinicopathological features and prognostic significance are still unclear. Here we present three AML cases with cryptic rearrangements of chromosomes 8 and 21 without standard RUNX1/RUNX1T1. Materials and Methods: Conventional karyotyping and fluorescence in situ hybridization and/or spectral karyotyping of the pretreatment bone marrow aspirate of de novo AML patients were performed to delineate chromosomal abnormalities. Results: We identified three cases with novel variants of t(8;21); der(13)t(8;21;13), isodicentric derivative 8 with chromosome 21[,+idicder(8)(q11.1)t(8;21)(q22;q11.1)] and der(21)t(8;12;21)(q22;q?;q22). Conclusion: AML with t(8;21)(q22;q22);RUNX1-RUNX1T1 forms a distinct WHO subcategory and hence the identification of variants or unusual translocations associated with t(8;21) deserves more attention. Contribution to the variant/ unusual t(8;21) database will further refine the risk stratification and may help to significantly advance the current treatment regimen.

Histiocytic Sarcoma: Clinical Features and Outcomes of Patients Treated at a Tertiary Cancer Care Center.

Histiocytic sarcoma (HS) is an extremely rare histiocytic disorder of unknown etiology. It is not a true sarcoma and is named so, due to the pathological resemblance to mature histiocytes. The clinical presentation of HS is diverse and is related to the involved organs. Due to its aggressive nature, with poor prognosis and lack of a standard treatment regimen of choice, its diagnosis and management pose a challenge to the clinician. Limited literature is available on the management of this entity. Here, we report four patients with HS, diagnosed over 15 years in a tertiary cancer center, with varied clinical presentation, management, and outcomes. The first patient presented with a localized unresectable esophageal mass. He was treated with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) combination chemotherapy and attained complete remission. The second patient had a painless mass of the hand, treated with wide excision and adjuvant Radiotherapy. She is disease-free for the past 12 years. The third patient had presented with an anterior mediastinal mass. He had progressive disease on chemotherapy. The fourth patient had multifocal disease with generalized lymphadenopathy. She was treated with CHOP chemotherapy and is now disease-free at 13 months. To summarize, the patients with the localized resectable disease did well, with surgical excision and adjuvant radiotherapy, while patients with the multifocal disease did well on CHOP chemotherapy. The take-home message from this case series is - CHOP off whenever you can and if not give CHOP to chop off the disease.

Serum Free Light Chain Assay as a Prognostic Marker in Patients with Aggressive B-Cell Non-Hodgkin's Lymphoma: Impact on Survival Outcome.

T.M. AnoopBackground The role of serum free light chain (FLC) as a prognostic biomarker in lymphoproliferative diseases is being increasingly studied. In this study we present the 5-year survival outcome for patients with aggressive B-cell non-Hodgkin's lymphoma (NHL) and their relation to FLC and other known prognostic markers. Materials and Methods This is a prospective study conducted in patients diagnosed with aggressive B-cell NHL. Serum FLC level and ratio were estimated prior to initiation of treatment. Results A total of 100 patients were included in the study from December 2013 to December 2015 with a median age of 53 years. Thirty-eight patients (38%) had elevated FLC level of which 26% were polyclonal and 12% were monoclonal elevations. Abnormal FLC ratio was noted in 12% patients. Median follow-up duration of the study was 75 months. Five-year relapse-free survival (RFS) for the study population was 54.4%. Five-year RFS was 64.1% for early stage and 48.2% for advanced stage diseases ( p = 0.05). The RFS was significantly better in age less than 60 years (59.5% vs 43.8%, p < 0.001). Five-year overall survival (OS) was 61.3%. OS was significantly better in younger patients (73.6% vs 33.4%, p < 0.001), with International Prognosis Index score of 0 to 2 (87.4% vs 26.7%, p < 0.001). Patients with elevated FLC had inferior RFS (50% vs 71.4%, p = 0.04). Abnormal FLC ratio also strongly corresponded to inferior RFS (54.5% vs 66.2%, p = 0.001). OS was also significantly inferior in patients with abnormal FLC ratio (72.6% vs 63.6%, p = 0.001). Conclusion In patients with newly diagnosed aggressive B-cell NHL, elevated FLC levels and abnormal FLC ratio were significantly associated with inferior survival.

Early Normalization of Free Light Chains Predicts Better Outcomes in Patients with Multiple Myeloma.

Background: The half-life of free light chain is short and can be used as an early marker for tumor response in patients with multiple myeloma [MM]. This prospective study is aimed at evaluating whether early light chain response can predict response to treatment in patients with MM. Materials and Methods: Thirty six patients with a diagnosis of MM and with an abnormal to normal light chain ratio of > 10 were included in this study. Results: The median age at presentation was 56 years. Fourteen patients had lambda light chain disease, whereas 22 patients had kappa light chain disease. Twenty-four patients [66.6%] had reduction of abnormal to normal light chain ratio to < 10 after 2 cycles, of whom 15 [62.5%] achieved a CR or VGPR after 6 cycles. Among 12 patients who did not have reduction of abnormal to normal light chain ratio to < 10, only 1 patient achieved CR while 11 patients [91.6%] achieved a PR or less[Fishers exact p=0.004]. Median follow-up was 13 months. Median progression-free survival for the entire cohort was 15 months. One-year Progression-Free Survival was 77% vs 57.1%, [p= 0.008], respectively for patients with early normalization and those who did not show early normalization. Conclusion: Early light chain response after 2 cycles of chemotherapy is a good predictor for treatment response in patients with MM treated with bortezomib based chemotherapy. Treatment intensification based on early light chain response merits further evaluation in a prospective trial.

Histone chaperone HIRA dictate proliferation vs differentiation of chronic myeloid leukemia cells.

Abnormal proliferation and disrupted differentiation of hematopoietic progenitors mark leukemia. Histone cell cycle regulator A (HIRA), a histone chaperone, regulates hemogenic to hematopoietic transition involved in normal hematopoiesis. But, its role remains unexplored in leukemia, a case of dysregulated hematopoiesis. Here, the Cancer Cell Line Encyclopedia database analysis showed enhanced HIRA mRNA expression in cells of hematopoietic and lymphoid origin with maximal expression in the chronic myeloid leukemia (CML) cell line, K562. This observation was further endorsed by the induced expression of HIRA in CML patient samples compared to healthy individuals and Acute Myeloid Leukemia patients. Downregulation of HIRA in K562 cells displayed cell cycle arrest, loss in proliferation, presence of polyploidy with significant increase in CD41+ population thereby limiting proliferation but inducing differentiation of leukemia cells to megakaryocyte fate. Induced megakaryocyte differentiation of mouse Hira-knockout hematopoietic progenitors in vivo further confirmed the in vitro findings in leukemia cells. Molecular analysis showed the involvement of MKL1/GATA2/H3.3 axis in dictating differentiation of CML cells to megakaryocytes. Thus, HIRA could be exploited for differentiation induction therapy in CML and in chronic pathological conditions involving low platelet counts.

Lymphoblastic lymphoma of the palate.

Lymphoblastic lymphomas are neoplasms of immature or precursor lymphoid cells with no or limited bone marrow involvement, whose clinical presentation varies according to the immunophenotype. While mediastinal involvement is predominant in T-lymphoblastic lymphomas, B-lymphoblastic lymphomas frequently involve nodal sites. Extranodal presentation of B-lymphoblastic lymphomas is extremely rare. We present the case of a 49-year-old man with B-lymphoblastic lymphoma of the hard palate. The patient was treated with the R-Hyper CVAD regimen and is on maintenance chemotherapy. This is the first reported case of B-lymphoblastic lymphoma arising in the hard palate.

Isolated Intracranial Myeloid Sarcoma Occurring as Relapse in Acute Myeloid Leukemia.

Myeloid sarcoma (MS) or chloroma is a rare extramedullary tumor composed of extramedullary proliferation of blasts of granulocytic, monocytic, erythroid, or megakaryocytic lineage occurring at sites outside the bone marrow. MS occurs in 2%-8% of patients with acute myeloid leukemia (AML), sometimes it occurs as the presenting manifestation of relapse in a patient in remission. We describe the case of a young male with AML in remission for 6 years presenting with central nervous system symptoms. Magnetic resonance imaging showed an extra-axial altered intensity lesion in the parasagittal parietal region, infiltrating anterosuperiorly into anterior falx, and posterosuperior aspect of the superior sagittal sinus. A biopsy from the lesion was diagnostic of MS which was positive for myeloperoxidase. He did not have any other sites of disease. He has received chemotherapy with FLAG (Fludarabine, Cytosine arabinoside) followed by cranial irradiation and is in complete remission.

Ewing's sarcoma of the trachea in an adolescent girl.

Primitive neuroectodermal tumors (PNET) are aggressive neoplasms of neuroectodermal origin. Although they are known to arise in a host of locations, involvement of the trachea has rarely been reported. We describe an adolescent girl who presented with stridor and was diagnosed with PNET of the trachea. She is in remission following treatment with combination chemotherapy and local radiotherapy.

Mixed phenotypic acute leukemia with leukemia cutis and neuroleukemiosis.

Leukemia cutis and neuroleukemiosis are two rare extramedullary manifestations of acute leukemia. We report a 32-year-old woman with multiple skin lesions and painful peripheral neuropathy. Bone marrow biopsy and skin biopsy confirmed the diagnosis of mixed phenotypic acute leukemia. After induction chemotherapy, she attained marrow remission, her skin lesion resolved completely, and her neurologic symptoms significantly improved.

B-lymphoblastic lymphoma of the rectum.

Lymphoblastic lymphoma is a neoplasm of immature cells committed to the B-cell or T-cell lineage. B-lymphoblastic lymphoma usually involves lymph nodes and extranodal sites, such as the skin, bone, and soft tissue. The rectum is a very rare site of involvement in B-lymphoblastic lymphoma. We describe a 26-year-old man who presented with bleeding per rectum and fecal incontinence. Endoscopy showed a large nodular friable lesion narrowing the entire rectal lumen. Biopsy was diagnostic of B-lymphoblastic lymphoma. He was started on chemotherapy with the Berlin-Frankfurt-Münster protocol and achieved complete remission after induction chemotherapy. This is the first report of B-lymphoblastic lymphoma presenting as a rectal lesion in the world literature.

Rhabdomyosarcoma of the Vagina in an Adolescent Girl.

BACKGROUND: Gynecologic neoplasms are rare in children and represent only less than 5% of all childhood tumors. Rhabdomyosarcoma (RMS) of the female genital tract of children accounts for only 3.5% of the cases. CASE: A 16-year-old adolescent presented with a proliferating growth and foul smelling discharge from her vagina, which, on biopsy was diagnosed as RMS. She received chemotherapy and radiation to the primary site. She is alive in remission at 8 years, and with normal menstrual function. SUMMARY AND CONCLUSION: RMS of the vagina is a rare, but highly curable tumor in adolescent girls. Any abnormal vaginal bleeding in girls should be promptly investigated using pelvic examination and appropriate imaging. An organ-preserving approach should be considered in these patients.

Primitive neuroectodermal tumors of the kidney.

Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) rarely occurs as a primary renal tumor. The disease affects young adults and children and has an aggressive course. The clinical presentation and imaging of these tumors are nonspecific, and they often present at an advanced stage. We present the clinical features, imaging, diagnosis, and treatment of 7 cases of renal PNET (4 men, 3 women; median age, 32 years). Common presenting symptoms were flank or abdominal pain and a mass in the abdomen. On imaging, a large heterogenous infiltrating renal mass with areas of calcification, hemorrhage, and necrosis and tumor thrombus can give a clue to the diagnosis of renal PNET. Immunohistochemistry and molecular studies are essential to confirm the diagnosis. The prognosis of renal ES/PNET is generally poor. Radical nephrectomy combined with chemotherapy and radiotherapy is the standard treatment for renal PNET. An early and accurate diagnosis is crucial for the proper management of these aggressive tumors.

Synovial Sarcoma of the Larynx: Report of a Case and Review of Literature.

Sarcomas account for less than 1% of malignant neoplasms arising in the head and neck in adults. Laryngeal synovial sarcoma is an extremely rare form of laryngeal malignancy with less than 20 cases reported in the literature. We report the case of a 48-year-old man with synovial sarcoma of the larynx. He underwent excision of the tumor followed by radiation. He is alive in remission at 36 months. The literature on synovial sarcoma of the larynx is reviewed.

68Ga-PSMA PET/CT in Osteosarcoma in Fibrous Dysplasia.

Fibrous dysplasia (FD) is a benign bone lesion with a rare but potential for malignant transformation. Neither Tc-MDP nor F-FDG PET/CT can differentiate between FD and areas of malignant transformation in FD. We described a case of osteosarcoma developing in FD with selective uptake of tracer in malignant transformation areas demonstrated on a Ga-PSMA PET/CT scan. Our case highlights the ability of Ga-PSMA PET/CT to map tumor neoangiogenesis in osteosarcoma arising in FD, which can have potential implications in prognostication, possibility of antiangiogenesis-based therapeutic options, and in response assessment following chemotherapy.

Blood group change in acute myeloid leukemia.

Blood group antigens are either sugars or proteins found attached to the red blood cell membrane. ABO blood group antigens are the most clinically important antigens because they are the most immunogenic. As red blood cell antigens are inherited traits, they are usually not altered throughout the life of an individual. There have been occasional case reports of ABO blood group antigen change in malignant conditions. We report two such cases of ABO antigen alteration associated with acute myeloid leukemia. These patients had suppression of their blood group antigens during their leukemic phase, and the antigens were reexpressed when the patients attained remission.

Subcutaneous panniculitis-like T-cell lymphoma.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is a rare form of skin lymphoma that is localized primarily to the subcutaneous adipose tissue without involvement of the lymph nodes. Clinically, the skin lesions mimic lipomas, while histologically they resemble panniculitis. We report a case of a young woman with SPTCL. She achieved complete remission after combination chemotherapy.

Lymphoblastic Lymphoma Presenting as Bilateral Ovarian Mass in an Adolescent Girl.

BACKGROUND: Lymphomas rarely involve the genital tract and non-Hodgkin lymphoma (NHL) presenting as ovarian tumor is rare. Precursor B-cell lymphoblastic lymphoma arising from the ovary is extremely rare and to our knowledge, only 5 cases have been reported in the literature. CASE: A 15-year-old girl presented with bilateral ovarian masses, which, on biopsy proved to be precursor B-cell lymphoblastic lymphoma. She was treated with a Berlin-Frankfurt-Munster 90 protocol and she is alive in complete remission for more than 10 years. SUMMARY AND CONCLUSION: NHL of the ovary should also be considered as a differential diagnosis in adolescent and young adults with ovarian masses. Attempt to make a preoperative diagnosis is crucial because ovarian NHL responds well to chemotherapy and has a good prognosis.