Unusual Case of Progressive Multifocal Leukoencephalopathy in a Patient With Sjögren Syndrome.

ABSTRACT: Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disease caused by reactivation of John Cunningham virus affecting typically subcortical and periventricular white matter of immunocompromised hosts (human immunodeficiency virus infection, hematologic malignancies). Cerebral hemispheric white matter is most commonly affected by lytic infections, leading to progressive damage to oligodendrocytes in the central nervous system. Neuroimaging usually highlights scattered foci of white matter hypodensity not attributable to contrast enhancement or mass effect. In contrast, we present an unusual case of PML predominantly affecting cervical spinal cord and brainstem in an immunocompetent host. This is a rare subset of PML case that can occur in association with connective tissue disorders (Sjögren Syndrome in this case), systemic lupus erythematosus being the most common. Progressive multifocal leukoencephalopathy should be considered in the differential diagnosis of spinal cord or brainstem lesions, particularly in the patients with connective tissue disorders.

Hepatocellular carcinoma: Clinicopathologic associations amidst marked phenotypic heterogeneity.

BACKGROUND: Hepatocellular carcinoma (HCC) is characterized by marked phenotypic and molecular heterogeneity. Clinico-morphologic phenotypes and associations are important surrogate markers of molecular aberrations; therefore have immense relevance for targeted therapy. There is paucity of published literature on critical analysis of HCC heterogeneity and morphological alliance. AIMS: To assess the heterogeneity and dominance of histomorphological features, and to explore clinicopathological associations in HCC. METHODS: Retrospective cross-sectional study of 217 HCC tissue specimens was performed for the assessment of prevalence of major histological patterns, cytological features, and clinicopathological correlation. RESULTS: Homogeneous architecture with a single dominant histological pattern was a rarity. Single pattern constituting ≥50 % of the tumour was found in less than 1/5th of the cases. Macrotrabecular HCC represented 9.2 % of cases. The simultaneous presence of 2-3 patterns or atypical variants and/ or cytological characteristics was recorded in 25 % and 30 % respectively. Significant clinicopathological associations: Pseudoglandular with microtrabecular pattern-cholestasis, showed better differentiation and early-stage; macrotrabecular pattern frequently occurred with pleomorphic giant cells, higher tumour stage, higher AFP levels; solid pattern often showed clear cells. Noticeable mutual exclusions were MD bodies with microtrabecular and pseudoglandular patterns; Compact pattern with neutrophilic clusters and cholestasis. Larger tumours were significantly more heterogeneous; however, heterogeneity did not correlate with outcome CONCLUSIONS: HCC displays immense heterogeneity with an amalgamation of different histomorphological patterns and features; nevertheless, there are certain reproducible associations and omissions. Tumor biopsies agree fairly well with large specimens. Characterization of phenotypic heterogeneity, dominance, associations, and exclusions in individual patients provides vital information.

Post Prostatectomy Pathologic Findings of Patients With Clinically Significant Prostate Cancer and no Significant PI-RADS Lesions on Preoperative Magnetic Resonance Imaging.

OBJECTIVES: We present postprostatectomy pathology results from a series of prostate cancer (Pca) Gleason grade group ≥2 patients who did not have findings suggestive of cancer on preoperative pelvic magnetic resonance imaging (MRI). METHODS: We performed an institutional retrospective study of prostate magnetic resonance imaging (MRI) examinations done from October 2015 to February 2018. We identified patients who underwent prostatectomy for Pca Gleason ≥3 + 4 diagnosed on prostate biopsy with no associated MRI findings suggestive of malignancy and analyzed their postprostatectomy pathologic findings and MRI imaging results. RESULTS: At our institution, 850 men with Pca received MRI between 2015 and 2018, and 156/850 patients received robotic-assisted radical prostatectomy. Thirty-three patients (33/156 = 21%) had negative MRI for PIRAD 3 or greater but had a biopsy showing significant Pca. Their mean (range) age was 62.7 (50-86) years. Their median (interquartile range) PSA, and PSA density were, 4.6 (3.7) ng/mL and 0.12 (0.05) ng/mL/cm2, respectively; all not significantly different from patients with visible lesions on MRI who underwent surgery. On post prostatectomy pathology, 27/33 (82%) men had Pca Gleason score 7 or greater. The most common pattern was infiltrative growth with cancer glands intermingling between benign glands. CONCLUSION: We describe the pathologic and imaging findings in an extensive series of men with clinically significant Pca with no significant lesions on preoperative MRI. Our results support the importance of patient counseling on the risk of missing significant Pca on MRI in isolation from other clinical variables.

Breast and prostate cancers harbor common somatic copy number alterations that consistently differ by race and are associated with survival.

BACKGROUND: Pan-cancer studies of somatic copy number alterations (SCNAs) have demonstrated common SCNA patterns across cancer types, but despite demonstrable differences in aggressiveness of some cancers by race, pan-cancer SCNA variation by race has not been explored. This study investigated a) racial differences in SCNAs in both breast and prostate cancer, b) the degree to which they are shared across cancers, and c) the impact of these shared, race-differentiated SCNAs on cancer survival. METHODS: Utilizing data from The Cancer Genome Atlas (TCGA), SCNAs were identified using GISTIC 2.0, and in each tumor type, differences in SCNA magnitude between African Americans (AA) and European Americans (EA) were tested using linear regression. Unsupervised hierarchical clustering of the copy number of genes residing in race-differentiated SCNAs shared between tumor types was used to identify SCNA-defined patient groups, and Cox proportional hazards regression was used to test for association between those groups and overall/progression-free survival (PFS). RESULTS: We identified SCNAs that differed by race in breast (n = 58 SCNAs; permutation p < 10- 4) and prostate tumors (n = 78 SCNAs; permutation p = 0.006). Six race-differentiated SCNAs common to breast and prostate found at chromosomes 5q11.2-q14.1, 5q15-q21.1, 8q21.11-q21.13, 8q21.3-q24.3, 11q22.3, and 13q12.3-q21.3 had consistent differences by race across both tumor types, and all six were of higher magnitude in AAs, with the chromosome 8q regions being the only amplifications. Higher magnitude copy number differences in AAs were also identified at two of these race-differentiated SCNAs in two additional hormonally-driven tumor types: endometrial (8q21.3-q24.3 and 13q12.3-q21.3) and ovarian (13q12.3-q21.3) cancers. Race differentiated SCNA-defined patient groups were significantly associated with survival differences in both cancer types, and these groups also differentiated within triple negative breast cancers based on PFS. While the frequency of the SCNA-defined patient groups differed by race, their effects on survival did not. CONCLUSIONS: This study identified race-differentiated SCNAs shared by two related cancers. The association of SCNA-defined patient groups with survival demonstrates the clinical significance of combinations of these race-differentiated genomic aberrations, and the higher frequency of these alterations in AA relative to EA patients may explain racial disparities in risk of aggressive breast and prostate cancer.

Unmasking lymphoma immune reconstitution inflammatory syndrome in a patient with pyrexia of unknown origin: a case report.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a constellation of inflammatory disorders that are unmasked after the initiation of anti-retroviral therapy (ART) in Human immunodeficiency virus (HIV) infected patients. Unmasking lymphoma IRIS is a relatively rare manifestation after initiation of anti-retroviral therapy. CASE PRESENTATION: We report a 44-year-old male with HIV on 4 months of ART presenting with pyrexia of unknown origin with a diagnosis of unmasking Hodgkin's lymphoma IRIS stage IV with B symptoms. This case portrays the importance of recognizing the possibility of Hodgkin's lymphoma as a possible manifestation of IRIS within the first 6 months of initiation of ART. CONCLUSION: Patients presenting with pyrexia of unknown origin and lymphadenopathy within the first 6 months of initiation of ART, lymphoma diagnosis should be on the high threshold of suspicion as portrayed by our case.

The Precision Prostatectomy: an IDEAL Stage 0, 1 and 2a Study.

OBJECTIVE: This study aimed to develop a preclinical model of prostate cancer (CaP) for studying focal/hemiablation of the prostate (IDEAL stage 0), and to use the information from the stage 0 investigation to design a novel focal surgical treatment approach-the precision prostatectomy (IDEAL stage 1/2a). METHODS: The IDEAL stage 0 study included simulation of focal/hemiablation in whole-mount prostate specimens obtained from 100 men who had undergone radical prostatectomies, but met the criteria for focal/hemiablation. The IDEAL stage 1/2a was a prospective, single-arm, Institutional Review Board-approved study of precision prostatectomy undertaken in eight men, who met the predetermined criteria. Criteria for both stages included (1) prostate-specific antigen (PSA) ≤15 ng/mL, (2) stage ≤cT2, (3) dominant unilateral lesion with Gleason ≤4+3 with any number of cores or % cores involved ipsilaterally on transrectal biopsy, (4) no primary Gleason ≥4 contralaterally on transrectal biopsy, and (5) preoperative erectile function score (International Index of Erectile Function (IIEF)-5) of ≥17 (out of 25) without PDE-5i (applicable only to the stage 1/2a study participants). Feasibility and safety of the precision prostatectomy technique, and short-term urinary, sexual and oncological outcomes were studied. RESULTS: Analysis of whole-mount specimens in the 100 men showed an index lesion (>1 cm in diameter) in all. Ninety-eight men had satellite lesions smaller than 0.5 cm∧3 in volume-46 on the side of the dominant lesions and 52 in the contralateral lobe. If the men in this modeling cohort had undergone focal ablation with a 5-10 mm untreated margin, all except one would have had at least Gleason 6 residual cancer. If they had undergone hemiablation with no untreated tissue on the ablated side, 56 men would have had residual cancer on the contralateral side, of whom 21 would have had clinically significant cancer (Gleason 7 or higher). If these men had undergone precision prostatectomy, with preservation of 5-10 mm of tissue on the non-dominant side, 10% and 4% would have had Gleason 3+4 and Gleason 4+3 disease left behind, respectively. For the stage 1/2a study, the median (IQR) age, PSA and IIEF-5 scores at the time of surgery were 54 (52-57) years, 4.4 (3.8-6.1) ng/mL and 24 (23-25), respectively. All eight patients were continent and sexually active at 12 months with a median IIEF-5 score of 21 (out of 25). At 24-30 months from surgery, the median PSA was 0.2 (range 0.1-0.7) ng/mL. Six men had undergone follow-up protocol biopsies, two, with undetectable PSA, had refused. Two men had residual Gleason 3+3 cancer, with PSA of 0.7 and 0.4 ng/mL, and remain on active surveillance. No man has undergone secondary whole-gland therapy. CONCLUSIONS: Examination of whole-mount radical prostatectomy specimens in men who fit the conventional criteria of focal/hemiablation showed that approximately 21%-68% of men would have clinically significant CaP in the untreated tissue. In a small development cohort, precision prostatectomy was technically feasible, with excellent postoperative functional recovery. At 30 months of follow-up, no patient had clinically significant residual cancer or required secondary treatment. Pending long-term follow-up, a risk-stratified surgical approach may avoid whole-gland therapy and preserve erectile function in the majority of men with intermediate-risk CaP.

Renal cell carcinoma staging: pitfalls, challenges, and updates.

Renal cell carcinoma (RCC) is unusual among cancers in that it often grows as a spherical, well-circumscribed mass. Increasing tumour size influences the pathological pT stage category within pT1 and pT2, with cutoffs of 40, 70 and 100 mm; however, with increasing size also comes a sharp increase in the likelihood of renal sinus or renal vein tributary invasion, such that clear cell RCC rarely reaches 70 mm without invading one of these. To clarify some previous challenges in assigning tumour stage, the American Joint Committee on Cancer 2016 tumor-node-metastasis classification has removed the requirements than vein invasion be recognised grossly and that vein walls contain muscle for the diagnosis of vein invasion. Renal pelvis invasion has also been added as an additional route to pT3a. Multinodularity or finger-like extensions from a renal mass should be viewed with great suspicion for the possibility of vein or renal sinus invasion, and, as tumour size increases to over 40-50 mm, thorough sampling of the renal sinus interface should always be undertaken. With increasing interest in adjuvant therapy in renal cancer, the pathologist's role in RCC staging will continue to be an important prognostic parameter and a tool for selection of patients for enrolment in clinical trials.

Updates in Pathologic Staging and Histologic Grading of Renal Cell Carcinoma.

The most important prognostic parameter in renal cell carcinoma is tumor stage. Although pathologic primary tumor (pT) categories are influenced by tumor size (pT1-pT2), critical elements (≥pT3) are dictated by invasion of structures, including renal sinus, perinephric fat, and the renal vein or segmental branches. Because this invasion can be subtle, awareness of the unique characteristics of renal cell carcinoma is critical for the pathologist to aid in clinical decision making. This review addresses challenges in pathologic stage and grade reporting and updates to the World Health Organization and American Joint Commission on Cancer classification schemes.

Pathological staging of renal cell carcinoma: a review of 300 consecutive cases with emphasis on retrograde venous invasion.

AIMS: Pathological staging of renal cell carcinoma (RCC) can be challenging compared to other cancer types, as invasion often manifests as finger-like protrusions into vascular spaces or renal sinus tissue. Although prior studies have shown larger tumour size to be correlated highly with renal sinus invasion, prospective data on evaluating pathological stage are limited. We evaluated a large series reported by one urological pathologist. METHODS AND RESULTS: Three hundred consecutive specimens were reviewed. Tumours larger than 5 cm were routinely sampled extensively or grossly re-reviewed when no extrarenal extension was identified on initial examination. Apparent multifocal disease was assessed critically for intravascular spread. Retrograde venous invasion was reported in 15 of 300 (5%) cases, 13 of 15 of which were clear cell RCC. Of a total of 163 specimens with clear cell histology, only five of 34 (15%) tumours 7 cm or larger were reported as pT2, all of which had an explanatory comment indicating the absence of definitive extrarenal spread. In contrast, 15 of 20 (75%) pT2 tumours were non-clear cell histology (papillary, chromophobe and translocation-associated). Comparing pT3a or higher tumours, the median tumour size in cases with retrograde venous invasion was 8.0 cm, compared to 6.2 cm in cases without retrograde venous invasion (P = 0.005). CONCLUSIONS: Our findings support that retrograde venous invasion should be considered carefully before diagnosing multifocal clear cell RCC, which is rare in the sporadic setting. In the absence of vascular invasion, multifocal clear cell papillary RCC can be a mimic. pT2 occurs more frequently with non-clear cell histology (particularly papillary or chromophobe RCC).

Chromophobe Renal Cell Carcinoma With Retrograde Venous Invasion and Gain of Chromosome 21: Potential Harbingers of Aggressive Clinical Behavior.

Occasionally, renal cell carcinoma (RCC) with renal vein extension spreads against the flow of blood within vein branches into the kidney, forming multifocal nodules throughout the renal parenchyma. These foci are not regarded as multiple tumors but rather reverse spread of tumor along the venous system. This intravascular spread has previously been reported in clear cell RCC and RCC unclassified. However, to our knowledge, this has never been reported in chromophobe RCC. Chromophobe RCC is a unique histologic subtype of renal cancer, generally thought to have less aggressive behavior. However, it nonetheless has the potential to undergo sarcomatoid dedifferentiation, which is associated with poor prognosis. We report a unique case of a 65-year-old man with chromophobe RCC (pT3a) showing classic morphology (nonsarcomatoid), yet presenting with retrograde venous invasion and hilar lymph node metastasis at the time of right radical nephrectomy. Fluorescence in situ hybridization revealed gain of chromosome 21 with loss of multiple other chromosomes. Partial hepatectomy was performed to resect metastatic RCC 7 months after nephrectomy, revealing chromophobe RCC with classic morphology. Bone biopsy confirmed skeletal metastases 38 months after initial diagnosis. Although invasion of the renal vein and retrograde venous invasion are characteristically seen in clear cell RCC, this unusual phenomenon may also occur in chromophobe RCC, despite its unique tumor biology. This and gain of chromosome 21, which was postulated to be associated with aggressive behavior in a previous report, were associated with adverse behavior in our patient, who had short-term progression to multi-organ metastatic disease.

Unclassified hemangioma-like renal cell carcinoma: a potential diagnostic pitfall.

Recently, rare renal cell carcinomas (RCCs) have been reported to closely mimic hemangioma; however, these have been largely recognizable as clear cell RCC. Conversely, true hemangiomas of the kidney are also increasingly recognized. We report a 62-year-old woman who underwent partial nephrectomy for a hemangioma-like RCC without appreciable clear cell morphology. Immunohistochemistry revealed luminal structures that stained positively for cytokeratin, cytokeratin 7, carbonic anhydrase IX, PAX8, and high-molecular-weight keratin, admixed with a CD34-positive, CD31-positive, and ERG-positive complex network of vessels. Staining was minimal for α-methyl-acyl-coA-racemase and EMA, and absent for GATA3, HMB45, melan-A, and cathepsin K. Fluorescence in situ hybridization revealed no TFE3 or TFEB rearrangement, 3p deletion, or trisomy 7 or 17. This case adds to the spectrum of hemangioma-like RCC with differing morphology and immunophenotype. Further study will determine whether this represents a distinct entity or an unusual pattern of degenerative changes in an existing entity.

Assessment of aerosols optical properties and radiative forcing over an Urban site in North-Western India.

The present work is aimed to analyze aerosols optical properties and to estimate aerosol radiative forcing (ARF) from January to December 2013, using sky radiometer data over Rohtak, an urban site in North-Western India. The results reveal strong wavelength dependency of aerosol optical depth (AOD), with high values of AOD at shorter wavelengths and lower values at longer wavelength during the study period. The highest AOD values of 1.07 ± 0.45 at 500 nm were observed during July. A significant decline in Ångström exponent was observed during April-May, which represents the dominance of coarse mode particles due to dust-raising convective activities. Aerosols' size distribution exhibits a bimodal structure with fine mode particles around 0.17 µm and coarse mode particles with a radius around 5.28 µm. Single scattering albedo values were lowest during November-December at all wavelengths, ranging from 0.87 to 0.76, which corresponds to the higher absorption during this period. Aerosols optical properties retrieved during observation period are used as input for SBDART (Santa Barbara DISORT Atmospheric Radiative Transfer) to estimate the direct ARF at the surface, in the atmosphere and at the top of the atmosphere (TOA). The ARF at the TOA, surface and in the atmosphere are found to be in the range of -4.98 to -19.35 W m-2, -8.01 to -57.66 W m-2 and +3.02 to +41.64 W m-2, respectively. The averaged forcing for the whole period of observations at the TOA is -11.26 W m-2, while at the surface it is -38.64 W m-2, leading to atmospheric forcing of 27.38 W m-2. The highest (1.168 K day-1) values of heating rate was estimated during November, whereas the lowest value (0.084 K day-1) was estimated for the February.