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.

Lymphoma and Differentiated Thyroid Cancer: A Case Series.

Occurrences of lymphoma and differentiated thyroid cancer are rare. Usually, involvement of the thyroid gland is seen as a part of extranodal involvement or as a part of radiation-induced malignant transformation in previously treated lymphoma patients. The incidence of synchronous hematological malignancy with differentiated thyroid cancer is 7%. The synchronous occurrence of differentiated thyroid cancer and lymphoma poses a significant diagnostic and treatment dilemma. Here we report a case series of four patients with lymphoma and differentiated thyroid cancer. All four patients had lymphoma treated first followed by definitive management of thyroid malignancy.

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.

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.

Brodie's Abscess: A Diagnostic Conundrum.

Atraumatic limb pain in a child raises concerns in a medical setting. That is how a typical case of Brodie's abscess presents, having pain without any other symptoms of systemic illness. Assessment and investigations might also not reveal anything significant unless adequate imaging is done. Although Brodie's abscess has a very low rate of complications and morbidity/disability, it is important that such a presentation is assessed clinically with a diagnosis of Brodie's abscess in mind to ensure an uneventful and good outcome. We illustrate in this case report a similar presentation of an 11-year-old girl who had multiple visits to primary care. She was then assessed through radiological imaging. By the time of her diagnosis, her abscess had protruded through the skin. Thankfully management was done swiftly after identification and the final outcome was good with complete recovery.

Epidermal growth factor receptor exon 20 mutation in lung cancer: types, incidence, clinical features and impact on treatment.

BACKGROUND: There are limited data available on the treatment and outcome of epidermal growth factor receptor (EGFR) exon 20-mutated lung cancer patients. Hence, we planned an analysis of the demographic details, clinical profile and survival of lung cancer patients with exon 20 mutations. We compared our results to patients with EGFR tyrosine kinase inhibitor (TKI)-sensitizing activating and EGFR/anaplastic lymphoma kinase (ALK)-negative mutations. METHODS: This was a retrospective analysis of lung cancer patients who were treated at our center between January 2010 and August 2014. We reviewed the results of EGFR mutation testing by real-time polymerase chain reaction and Sanger sequencing. We also reviewed the data relating to baseline demographics, clinical profile, patient treatment and outcome measures in terms of response and overall survival (OS). RESULTS: A total of 580 patients fulfilled the selection criteria. In all, 227 (39.1%) patients had EGFR TKI-sensitizing activating mutations, 20 (3.4%) patients had exon 20 insertion mutations and 333 patients were EGFR/ALK mutation negative (57.5%). The median OS was 5 months (95% confidence interval [CI] 0.17-9.8 months) in exon 20 insertion mutations, 16.1 months (95% CI 12.8-19.5 months) in EGFR TKI-sensitizing activating mutations and 10 months (95% CI 7.9-12.1 months) in EGFR/ALK mutation-negative patients. The median OS was significantly better for the EGFR TKI-sensitizing activating mutation group (P=0.000, log-rank test) and for the EGFR/ALK-negative group (P=0.037, log-rank test) compared to the exon 20-mutated group. CONCLUSION: Exon 20 mutation results in a poorer OS prognosis compared to EGFR- and ALK-negative patients and patients harboring EGFR TKI-sensitizing activating mutations. The incidence of de novo exon 20 insertions was 3.4%. Different types of exon mutations seem to have different outcomes.

Effective Management of Advanced Angiosarcoma by the Synergistic Combination of Propranolol and Vinblastine-based Metronomic Chemotherapy: A Bench to Bedside Study.

BACKGROUND: Angiosarcomas are rare malignant tumors of vascular origin that represent a genuine therapeutic challenge. Recently, the combination of metronomic chemotherapy and drug repositioning has been proposed as an attractive alternative for cancer patients living in developing countries. METHODS: In vitro experiments with transformed endothelial cells were used to identify synergistic interactions between anti-hypertensive drug propranolol and chemotherapeutics. This led to the design of a pilot treatment protocol combining oral propranolol and metronomic chemotherapy. Seven consecutive patients with advanced/metastatic/recurrent angiosarcoma were treated with this combination for up to 12months, followed by propranolol-containing maintenance therapy. FINDINGS: Gene expression analysis showed expression of ADRB1 and ADRB2 adrenergic receptor genes in transformed endothelial cells and in angiosarcoma tumors. Propranolol strongly synergized with the microtubule-targeting agent vinblastine in vitro, but only displayed additivity or slight antagonism with paclitaxel and doxorubicin. A combination treatment using bi-daily propranolol (40mg) and weekly metronomic vinblastine (6mg/m(2)) and methotrexate (35mg/m(2)) was designed and used in 7 patients with advanced angiosarcoma. Treatment was well tolerated and resulted in 100% response rate, including 1 complete response and 3 very good partial responses, based on RECIST criteria. Median progression-free and overall survival was 11months (range 5-24) and 16months (range 10-30), respectively. INTERPRETATION: Our results provide a strong rationale for the combination of ß-blockers and vinblastine-based metronomic chemotherapy for the treatment of advanced angiosarcoma. Furthermore, our study highlights the potential of drug repositioning in combination with metronomic chemotherapy in low- and middle-income country setting. FUNDING: This study was funded by institutional and philanthropic grants.

Regorafenib in gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the GI tract and constitute less than 1% of all digestive tract tumors--the stomach is the most common site. Regorafenib is a multi-tyrosine kinase inhibitor with regulatory approvals granted for colorectal cancers and GIST. The US FDA granted approval for the use of regorafenib in February 2013 in patients with advanced GIST for those who had failed on imatinib and sunitinib. This was based on a pivotal Phase III double-blind placebo controlled randomized trial that showed that there was a significant improvement in progression-free survival for patients on regorafenib.

Regorafenib: carving a niche in the crowded therapeutic landscape.

The oral multikinase inhibitor regorafenib targets both tumor cell proliferation and vasculature and is active in heavily pretreated patients with metastatic colorectal cancer, for which the US FDA granted its approval in September 2012. The benefit for regorafenib was seen in these patients in most prespecified subgroups. The drug is also being used in other tumor types where it has shown exciting potential especially in gastrointestinal stromal tumors. The drug is well tolerated but requires close monitoring during administration. Common side effects include asthenia/tiredness, loss of appetite, hand-foot skin syndrome, diarrhea, mucositis, weight loss, infections, hypertension and rash. Serious adverse events to look out for are liver toxicity, hemorrhage and gastrointestinal perforation. Biomarker data should help us to optimize the use of these drugs to select which patients are most likely to benefit.