Splenic surprise in a case of renal cell carcinoma: Unusual case or association?

Littoral cell angioma (LCA) is a rare benign tumor originating exclusively from the venous sinus lining cells of the splenic red pulp. These cells are unique in having a distinctive hybrid endothelial/histiocytic phenotype. Also, there are reports of the association of LCA with internal malignancies. We present a case report highlighting an unusual association of LCA with conventional renal cell carcinoma (RCC), masquerading as a metastatic lesion. Knowledge of such an association is necessary to avoid misdiagnosis and prevent potential overtreatment.

High-dose salvage re-irradiation in recurrent/progressive adult diffuse gliomas: development of a novel prognostic scoring system.

PURPOSE: Over the past two decades, high-dose salvage re-irradiation (re-RT) has been used increasingly in the multimodality management of adults with recurrent/progressive diffuse glioma. Several factors that determine outcomes following re-RT have been incorporated into prognostic models to guide patient selection. We aimed to develop a novel four-tiered prognostic model incorporating relevant molecular markers from our single-institutional cohort of patients treated with high-dose salvage re-RT for recurrent/progressive diffuse glioma. MATERIAL AND METHODS: Various patient, disease, and treatment-related factors impacting upon survival following salvage re-RT were identified through univariate analysis. Each of these prognostic factors was further subdivided and assigned scores of 0 (low-risk), 1 (intermediate-risk), or 2 (high-risk). Scores from individual prognostic factors were added to derive the cumulative score (ranging from 0 to 16), with increasing scores indicating worsening prognosis. RESULTS: A total of 111 adults with recurrent/progressive diffuse glioma treated with salvage high-dose re-RT were included. We could assign patients into four prognostic subgroups (A=15 patients, score 0-3); (B=50 patients, score 4-7); (C=33 patients, score 8-10); and (D=13 patients, score 11-16) with completely non-overlapping survival curves suggesting the good discriminatory ability. Post-re-RT survival was significantly higher in Group A compared to groups B, C, and D, respectively (stratified log-rank p-value <0.0001). CONCLUSION: There exists a lack of universally acceptable 'standard-of-care' salvage therapy for recurrent/progressive diffuse glioma. A novel four-tiered prognostic scoring system incorporating traditional factors as well as relevant molecular markers is proposed for selecting patients appropriately for high-dose salvage re-RT that warrants validation in a non-overlapping cohort.

High-dose salvage re-irradiation for recurrent/progressive adult diffuse glioma: healing or hurting?

PURPOSE: To report survival outcomes and identify prognostic factors of salvage re-irradiation (re-RT) in recurrent/progressive glioma. METHODS: Medical records of patients treated with high-dose re-RT as part of multi-modality salvage therapy for recurrence/progression of adult diffuse glioma from 2010 to 2019 were analyzed retrospectively. RESULTS: A total of 111 patients developing recurrent/progressive high-grade glioma after adequate upfront treatment at initial diagnosis were included. The first course of radiotherapy (RT) had been delivered to a median dose of 59.4 Gy with an inter-quartile range (IQR) of 54-60 Gy. Median time to recurrence/progression was 4.3 years (IQR = 2.3-7.4 years) while the median time to re-RT was 4.8 years (IQR = 3.6-7.9 years). Re-RT was delivered with intensity-modulated radiation therapy (IMRT) using 1.8 Gy/fraction to a median dose of 54 Gy (IQR = 50.4-55.8 Gy) for a cumulative median equivalent dose in 2-Gy fractions (EQD2) of 104.3 Gy (IQR = 102.6-109.4 Gy). At a median follow-up of 14 months after re-RT, the 1-year Kaplan-Meier estimates of post-re-RT progression-free survival (PFS) and overall survival (OS) were 42.8 and 61.8%, respectively. Univariate analysis identified histological grade at recurrence/progression; histological subtype; disease-free interval (DFI) and time interval between both courses of RT; performance status at re-RT; dose at re-RT and cumulative EQD2; isocitrate dehydrogenase (IDH) mutation; and O6-methyl-guanine DNA methyl transferase (MGMT) gene promoter methylation as significant prognostic factors. Preserved performance status, longer DFI, prolonged time interval between both courses of RT, and presence of IDH mutation were associated with significantly improved PFS on multi-variate analysis. However, only performance status retained independent prognostic significance for OS on multi-variate analysis. Post-treatment changes were seen in 33 (30%) patients on follow-up imaging, with higher cumulative dose (EQD2 ≥ 104.3 Gy) being associated with increased risk of post-re-RT pseudo-progression. CONCLUSION: This clinical audit reports encouraging survival outcomes and identifies key prognostic factors associated with high-dose salvage re-RT in recurrent/progressive glioma.

Oral administration of 3,3'-diselenodipropionic acid prevents thoracic radiation induced pneumonitis in mice by suppressing NF-kB/IL-17/G-CSF/neutrophil axis.

The incidence of symptomatic radiation induced lung pneumonitis (RILP), a major dose limiting side effect of thoracic radiotherapy, is in the range of 15-40%. Therapeutic options for the prevention and treatment of RILP are limited. Hence there is a need for developing novel radioprotectors to prevent RILP which can be patient compliant. This study sought to evaluate the efficacy of oral 3,3'-diselenodipropionic acid (DSePA), a novel selenocystine derivative to prevent RILP. C3H/HeJ (pneumonitis responding) mice received a single dose of 18 Gy, whole thorax irradiation and a subset were treated with DSePA orally (2.5 mg/kg), three times per week beginning 2 h post irradiation and continued till 6 months. DSePA delayed onset of grade ≥ 2 RILP by 45 days compared to radiation control (~105 versus ~60 days). It also reversed the severity of pneumonitis in 3/10 radiation treated mice leading to significant improvement in asymptomatic survival compared to radiation control (~180 versus ~102 days). DSePA significantly (p < 0.05) reduced the radiation-mediated infiltration of polymorphonuclear neutrophils (PMN) and elevation in levels of cytokines such as IL1-ß, ICAM-1, E-selectin, IL-17 and TGF-ß in the bronchoalveolar lavage fluid. Moreover DSePA lowered PMN-induced oxidants, maintained glutathione peroxidase activity and suppressed NF-kB/IL-17/G-CSF/neutrophil axis in the lung of irradiated mice. Additionally, this compound did not protect A549 (lung cancer) derived xenograft tumor from radiation exposure in SCID mice. DSePA offers protection to normal lung against RILP without affecting radiation sensitivity of tumors. It has the potential to be developed as an oral agent for preventing RILP.

Rechallenge temozolomide in glioma: A case series from India.

INTRODUCTION: Temozolomide (TMZ) is an integral part of upfront treatment of high-grade gliomas. It is administered postsurgery as concurrent therapy with radiation and subsequently as adjuvant chemotherapy for 6-12 cycles. It is unknown whether rechallenge of salvage TMZ in previously treated high-grade glioma has any efficacy. MATERIAL AND METHODS: Patients treated with salvage rechallenged TMZ between January 2015 and August 2016 were included for this retrospective analysis. SPSS version 20 was used for this analysis. Time to event analysis was performed using the Kaplan-Meier method. Progression-free survival (PFS) and overall survival (OS) were estimated. The maximum grade of toxicity was noted in accordance with CTCAE version 4.02. RESULTS: A total of 23 patients were selected for analysis with the median age being 43 years (range: 26-69 years). The tumor histopathology at baseline was astrocytoma Grade 2 in 1 patient, oligodendroglioma Grade 2 in 3 patients, anaplastic astrocytoma in 7 patients, anaplastic oligodendroglioma in 2 patients, and glioblastoma in 10 patients. All of them had previously received TMZ. The median numbers of previous TMZ cycles received were 6 (4-18). The median time to failure postlast treatment was 24 months (5-72 months). The median number of cycles of rechallenged salvage TMZ administered was 6 cycles (range: 1-18). Grade 3-4 myelosuppression was seen in 3 patients (13.4%). The median PFS was 459 days (95% confidence interval: 212.1-705.9). The median OS was 25 months. Six-month OS and 1-year OS were 81.4% and 75.1%, respectively. CONCLUSION: Rechallenge with TMZ in recurrent glioma that had previously responded to TMZ is associated with improvement in PFS and OS and has a sufficiently long disease-free interval.

A case series of salvage CCNU in high-grade glioma who have previously received temozolomide from a tertiary care institute in Mumbai.

INTRODUCTION: In our center, we routinely use CCNU (Lomustine) as salvage treatment in high-grade glioma patients who cannot afford bevacizumab. This exploratory analysis was done to report the efficacy and toxicity associated with this regimen. METHODS: Patients who were treated with salvage CCNU (postexposure to temozolomide) between January 2015 and August 2016 were included for this retrospective analysis. SPSS version 16 was used for this analysis. Time-to-event analysis was performed using the Kaplan-Meier method. Progression-free survival (PFS) and overall survival (OS) were estimated. The maximum grade of toxicity during salvage CCNU was noted in accordance with CTCAE version 4.02. RESULTS: In the stipulated period, 16 patients were selected for the analysis. The median age of patients was 43 years (range 15-63 years), and 12 (80.0%) patients were males. The Eastern Cooperative Oncology Group performance status was 0-1 in 11 patients (73.3%) and 2-4 in 4 patients (26.7%). The tumor histopathology at diagnosis was glioblastoma in ten patients (66.6%), anaplastic astrocytoma in four (26.7%) patients, and anaplastic oligodendroglioma in one patient (6.7%). Grade 3-4 myelosuppression was seen in five patients (33.3%). The median PFS and OS were 192 days (95% confidence interval [CI]: 156.0-227.5 days) and 282 days (95% CI: 190.9-373.1 days), respectively. CONCLUSION: CCNU is associated with modest treatment outcomes in recurrent/relapsed high-grade gliomas. The high rate of myelosuppression is a concern. Urgent efforts are required to improve upon these results.

High-dose salvage re-irradiation for recurrent/progressive adult diffuse glioma: healing or hurting?

Purpose To report survival outcomes and identify prognostic factors of salvage re-irradiation (re-RT) in recurrent/progressive glioma. Methods Medical records of patients treated with high-dose re-RT as part of multi-modality salvage therapy for recurrence/progression of adult diffuse glioma from 2010 to 2019 were analyzed retrospectively. Results A total of 111 patients developing recurrent/progressive high-grade glioma after adequate upfront treatment at initial diagnosis were included. The first course of radiotherapy (RT) had been delivered to a median dose of 59.4 Gy with an inter-quartile range (IQR) of 54-60 Gy. Median time to recurrence/progression was 4.3 years (IQR = 2.3–7.4 years) while the median time to re-RT was 4.8 years (IQR = 3.6–7.9 years). Re-RT was delivered with intensity-modulated radiation therapy (IMRT) using 1.8 Gy/fraction to a median dose of 54 Gy (IQR = 50.4–55.8 Gy) for a cumulative median equivalent dose in 2-Gy fractions (EQD2) of 104.3 Gy (IQR = 102.6–109.4 Gy). At a median follow-up of 14 months after re-RT, the 1-year Kaplan–Meier estimates of post-re-RT progression-free survival (PFS) and overall survival (OS) were 42.8 and 61.8%, respectively. Univariate analysis identified histological grade at recurrence/progression; histological subtype; disease-free interval (DFI) and time interval between both courses of RT; performance status at re-RT; dose at re-RT and cumulative EQD2; isocitrate dehydrogenase (IDH) mutation; and O6-methyl-guanine DNA methyl transferase (MGMT) gene promoter methylation as significant prognostic factors. Preserved performance status, longer DFI, prolonged time interval between both courses of RT, and presence of IDH mutation were associated with significantly improved PFS on multi-variate analysis. However, only performance status retained independent prognostic significance for OS on multi-variate analysis (AU)

Histopathological audit of splenectomies received at a cancer hospital.

BACKGROUND: There are few studies in the literature studying the yield of the diagnostic splenectomy in a suspicious lymphoma case. Moreover, their relevance is limited owing to low number of cases, the use of selection criteria, and the lack of modern ancillary studies. We present a histopathological review of splenectomy specimens referred as a case of lymphoma to our center. MATERIALS AND METHODS: The medical charts and laboratory data on all patients of all splenectomy specimens between the years 2003 and 2008 were reviewed. Morphological and immunohistochemical features were analyzed and the lymphomas were sub-typed in accordance to 2008 WHO Classification of Hematolymphoid Neoplasms. Flow cytometry immunophenotyping available in few cases was correlated. RESULTS: A total of 46 cases studied included splenic marginal zone lymphoma (SMZL) (19 cases), splenic diffuse large B-cell lymphoma (DLBCL) (14 cases), splenic diffuse red pulp B-cell lymphoma (DRP) (five cases), follicular lymphoma (three cases), hairy cell leukemia (HCL) (two cases), HCL variant (HCLv) (1 case), 1 case of hepatosplenic gamma delta T-cell lymphoma (TCL), and 1 cases of TCL (not otherwise specified). CONCLUSIONS: Predominantly splenic lymphoma is a biologically heterogeneous entity, ranging from low-grade SMZL to high-grade DLBCLs. TCLs constituted only 4% of all our cases. DRP, HCL, and HCLv have similar diffuse red pulp patterns of splenic involvement and are differentiated based on flow cytometric immunophenotyping. We had a large number of splenic DLBCL and none of these involved bone marrow (BM), while all other lymphoma subtypes had BM involvement (stage IV disease). Morphological and immunophenotypic (immunohistochemistry and flow cytometry) features of BM and splenectomy specimen need to be correlated to differentiate these rare though similar-looking entities with overlapping features.

Study of the morphological patterns and association of Epstein-Barr virus and human herpes virus 8 in acquired immunodeficiency deficiency syndrome-related reactive lymphadenopathy.

AIMS: Study of the morphological patterns of acquired immunodeficiency syndrome (AIDS)-related lymphadenopathy. SETTINGS AND DESIGN: We retrospectively selected cases of AIDS-related benign lymphadenopathy. Cases with lymphomas, frank granulomas and necrosis were excluded. We analyzed different morphological patterns and correlated these with immunophenotypic markers along with viral markers human herpesvirus 8-latency-associated nuclear antigen (HHV8-LANA), and Epstein-Barr virus-encoded ribonucleic acid (EBER) studies via in situ hybridization (EBER-ISH). MATERIALS AND METHODS: We present the morphological patterns of 13 cases of human immunodeficiency virus (HIV)-reactive lymph nodes and their clinical, hematological, biochemical and radiological parameters with special emphasis on the presence or absence of viral markers, including HHV8 and EBV. RESULTS: Common patterns included follicular hyperplasia only (five cases), mixed pattern of follicular hyperplasia with burnt-out germinal centres (four cases), completely atretic follicle (two cases), folliculolysis (11 cases), dumbbell-shaped follicles (three each), progressive transformation of germinal centers (four cases), T-zone expansion (two cases), Reed Sternberg (RS) cells like immunoblasts (two cases), Castleman's-like features with lollipop-like follicles (three cases) and a spindle cell prominence (one case). CD8+ T-cells were predominant in 12 cases. CD8+ T-cells were prominent in germinal centers (eight cases). Plasmablasts were seen in four cases within the perigerminal center area. Immunohistochemistry for HHV8, i.e. HHV8-LANA were negative in all cases while EBER was detected in 11 cases in the centrocyte-like B cells. Two cases of multicentric Castleman's disease expressed EBER; however, they did not express HHV8. CONCLUSION: The wide spectrum of histological changes in HIV-associated lymphadenopathy requires recognition. The histological changes can mimic those of other infective lymphadenitis, follicular lymphoma, Castleman's disease, progressive transformation of germinal center, Hodgkin's disease and spindle cell neoplasms. Presence of EBV is common while HHV8 was not seen.

Chordoid meningioma, an uncommon variant of meningioma: a clinicopathologic study of 12 cases.

AIMS: The study has been undertaken to document the clinicopathological features of 12 cases of chordoid meningioma, operated at All India Institute of Medical Sciences during 1996 to June 2005. METHODS: Clinical information was retrieved from the records of our Neurosurgery Department. The cases were stained with H&E, Periodic Acid Schiff (PAS) with and without diastase, mucicarmine, giemsa, toluidine blue, alcian blue, reticulin and Masson trichrome. Immunohistochemistry for pancytokeratin, epithelial membrane antigen, vimentin, glial fibrillary acidic protein, MIB-1, Leucocyte common antigen (LCA), CD-3 and CD-20 was done in all cases. RESULTS: The age ranged from 12-67 years (mean 34.2 years) and three of them occurred in < 18 years. Male to female ratio was 1:1.4. The duration of symptoms varied from 3.5 months to 5 years (mean 14.1 months). No systemic symptoms were noted. The location of tumor in eight cases was in the supratentorial and rest four in the infratentorial compartments. Interestingly, two cases were in intraventricular location, one in the lateral ventricle and other in the fourth ventricle. Microscopic examination showed lobulation with chordoid elements constituting > 95% of the entire tumor area in 11 of the total 12 cases. In one case, chordoid pattern constituted about 30% of the total tumor area; the rest was predominant meningothelial (60%). Mild to severe lymphoplasmacytic cell infiltrate was present in all cases. The histochemical stains showed the pattern of acidic mucin and interestingly revealed the presence of mast cells both in connective tissue stroma and epithelial cell islands. The inflammatory infiltrate was B-cell predominant. MIB-1 labeling index was low (< 2%) in all cases except two, which showed LI of 6% and 8%. Strong diffuse immunoreactivity for vimentin and focal positivity for epithelial membrane antigen was noted in all cases. CONCLUSIONS: Chordoid meningiomas are predominantly tumors of young adults with predilection for supratentorial location. Intraventricular location, absence of systemic manifestations despite the presence of abundant B-lymphocytes, presence of mast cells and low MIB-1 LI are some of the interesting findings in the present series, which need documentation. Hence, larger number of cases with adequate follow-up data need to be studied further to establish the clinical significance of this variant.