Fat Necrosis of the Breast: A Pictorial Review of the Mammographic, Ultrasound, CT, and MRI Findings with Histopathologic Correlation

Fat necrosis of the breast is a challenging diagnosis due to the various appearances on mammography, ultrasound, CT, PET-CT, and MRI. Although mammography is more specific, ultrasound is a very important tool in making the diagnosis of fat necrosis. MRI has a wide spectrum of findings for fat necrosis and the appearance is the result of the amount of the inflammatory reaction, the amount of liquefied fat, and the degree of fibrosis. While CT and PET-CT are not first line imaging examinations for the diagnosis of breast cancer or fat necrosis, they are frequently performed in the surveillance and staging of disease. Knowledge of how fat necrosis presents on these additional imaging techniques is important to prevent misinterpretation of the imaging findings. Gross and microscopic appearances of fat necrosis depend on the age of the lesion; the histologic examination of fat necrosis is usually straightforward. Knowledge of the variable appearances of fat necrosis on a vast array of imaging modalities will enhance a radiologist's accuracy in the analysis and interpretation of fat necrosis versus other diagnoses

Racial differences in the systemic inflammatory response to prostate cancer

Systemic inflammation may increase risk for prostate cancer progression, but the role it plays in prostate cancer susceptibility is unknown. From a cohort of over 10,000 men who had either a prostate biopsy or transurethral resection that yielded a benign finding, we analyzed 517 incident prostate cancer cases identified during follow-up and 373 controls with one or more white blood cell tests during a follow-up period between one and 18 years. Multilevel, multivariable longitudinal models were fit to two measures of systemic inflammation, neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR), to determine NLR and MLR trajectories associated with increased risk for prostate cancer. For both measures, we found no significant differences in the trajectories by case/control status, however in modeling NLR trajectories there was a significant interaction between race (white or Black and case-control status. In race specific models, NLR and MLR values were consistently higher over time among white controls than white cases while case-control differences in NLR and MLR trajectories were not apparent among Black men. When cases were classified as aggressive as compared to non-aggressive, the case-control differences in NLR and MLR values over time among white men were most apparent for non-aggressive cases. For NLR among white men, significant case-control differences were observed for the entire duration of observation for men who had inflammation in their initial prostate specimen. It is possible that, among white men, monitoring of NLR and MLR trajectories after an initial negative biopsy may be useful in monitoring prostate cancer risk

Categorizing renal oncocytic neoplasms on core needle biopsy: a morphologic and immunophenotypic study of 144 cases with clinical follow-up. Alderman MA, Daignault S, Wolf JS Jr, Palapattu GS, Weizer AZ, Hafez KS, Kunju LP, Wu AJ. Hum Pathol.September 2016;55:1–10

There is limited literature on renal oncocytic neoplasms diagnosed on core biopsy. All renal oncocytic neoplasm core biopsies from 2006 to 2013 were, retrospectively, reviewed. Morphologic features and an immunohistochemical panel of CK7, c-KIT, and S100A1 were assessed. Concordance with resection diagnosis, statistical analysis including a random forest classification, and follow-up were recorded. The postimmunohistochemical diagnoses of 144 renal oncocytic core biopsies were favor oncocytoma (67%), favor renal cell carcinoma (RCC) (12%), and cannot exclude RCC (21%). Diagnosis was revised following immunohistochemistry in 7% of cases. The most common features for oncocytoma (excluding dense granular cytoplasm) were nested architecture, edematous stroma, binucleation and tubular architecture; the most common features for favor RCC were sheet-like architecture, nuclear pleomorphism, papillary architecture, and prominent cell borders. High nuclear grade, necrosis, extensive papillary architecture, raisinoid nuclei, and frequent mitoses were not seen in oncocytomas. Comparing the pathologist and random forest classification, the overall out-of-bag estimate of classification error dropped from 23% to 13% when favor RCC and cannot exclude RCC was combined into 1 category. Resection was performed in 19% (28 cases) with a 94% concordance (100% of favor RCC biopsies and 90% of cannot exclude RCC biopsies confirmed as RCC; 83% of favor oncocytomas confirmed); ablation in 23%; and surveillance in 46%. Follow-up was available in 92% (median follow-up, 33 months) with no adverse outcomes. Renal oncocytic neoplasms comprise a significant subset (16%) of all core biopsies, and the majority (78%) can be classified as favor oncocytoma or favor RCC

Multilocular cystic renal cell carcinoma: pathological t staging makes no difference to favorable outcomes and should be reclassified. Bhatt JR, Jewett MA, Richard PO, Kawaguchi S, Timilshina N, Evans A, Alibhai S, Finelli A.J Urol. November 2016;196(5):1350–1355

We evaluated survival outcomes of cystic/multilocular cystic renal cell carcinomas in a long-term population-based study based on size and pathological tumor stage. We, retrospectively, reviewed a provincial cancer registry of all histologically proven cases of multilocular cystic renal cancers treated surgically between 1995 and 2008. All cases of cystic necrosis were excluded from study. Primary end points were overall- and cancer-specific survival estimated using Kaplan-Meier curves. Cox proportional hazards models of univariable and multivariable analyses were used to assess for factors associated with survival. Of 172 cases of cystic renal cancers 168 with complete data were analyzed, of which 98% were multilocular cystic. Median patient age at treatment was 55 years and 58% of the patients were male. More than 40% of cases were pT1b or greater, 15% were pT2 or greater and most cases were low Fuhrman grade (1–2). At a median follow-up of 9.75-years overall- and cancer-specific survival was 82.1% and 100%, respectively. No difference was noted in higher pathological T stage, size, or grade. Limitations inherent in population-based studies include under ascertainment of cause of death, lack of data on histologically benign cysts that are treated surgically and a lack of central pathology review. Multilocular cystic renal cell carcinoma has an excellent prognosis, which remains unchanged regardless of tumor size or pathological T stage. This suggests a strong case for nephron and adrenal sparing surgery when indicated, and nonsurgical management when feasible. As postoperative follow-up protocols are dictated by staging, we propose that for this entity pathological T staging should be abandoned or reassigned as pT1c to guide clinicians

Positive Surgical Margins Increase Risk of Recurrence after Partial Nephrectomy for High Risk Renal Tumors. Shah PH, Moreira DM, Okhunov Z, Patel VR, Chopra S, Razmaria AA, Alom M, George AK, Yaskiv O, Schwartz MJ, Desai M, Vira MA, Richstone L, Landman J, Shalhav AL, Gill I, Kavoussi LR. J Urol. 2016 Aug;196(2):327-34

The clinical significance of a positive surgical margin after partial nephrectomy remains controversial. The association between positive margin and risk of disease recurrence in patients with clinically localized renal neoplasms undergoing partial nephrectomy was evaluated. A retrospective multi-institutional review of 1,240 patients undergoing partial nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013 was performed. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of positive surgical margin with the log rank test and Cox models adjusting for tumor size, grade, histology, pathological stage, focality and laterality. The relationship between positive margin and risk of relapse was evaluated independently for pathological high risk (pT2-3a or Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups. A positive surgical margin was encountered in 97 (7.8%) patients. Recurrence developed in 69 (5.6%) patients during a median followup of 33 months, including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III-IV). A positive margin was associated with an increased risk of relapse on multivariable analysis (HR 2.08, 95% CI 1.09-3.97, p=0.03) but not with site of recurrence. In a stratified analysis based on pathological features, a positive surgical margin was significantly associated with a higher risk of recurrence in cases considered high risk (HR 7.48, 95% CI 2.75-20.34, p <0.001) but not low risk (HR 0.62, 95% CI 0.08-4.75, p=0.647). Positive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with adverse pathological features

Small Cell-like Change in Central Zone Histology—A New Observation Mimicking Cribriform Intraductal Prostatic Adenocarcinoma

A small cell-like change in prostate has been described in high-grade prostatic intraepithelial neoplasia (PIN), intraductal prostatic adenocarcinoma, and invasive prostate cancer. It occurs when these processes have a cribriform architecture. To date, small cell-like change has not been described in benign glands. Herein, I describe such a change in cribriform central zone histology from a radical prostatectomy with a spatially remote treatment naïve Grade Group 3 prostate cancer. The cancer did not have cribriform morphology or intraductal prostatic adenocarcinoma. The small cell-like change was positive for racemase in PIN-4 cocktail and no nuclei were highlighted by Ki-67. This is the first report of a small cell-like change in benign prostate tissue. Although rare, such finding in cribriform architecture of central zone histology can potentially be misinterpreted as a neoplastic process

Characteristics of the peritumoral pseudocapsule vary predictably with histologic subtype of T1 renal neoplasms. Jacob JM, Williamson SR, Gondim DD, Leese JA, Terry C, Grignon DJ, Boris RS.Urology. November 2015;86(5):956–961

To determine characteristics of the peritumoral pseudocapsule (PC) between renal tumor subtypes. The peritumoral PCs of 160 pT1 renal tumors were examined, including 60 clear cell renal cell carcinomas (RCCs), 50 papillary RCCs, 25 chromophobe RCCs, and 25 oncocytoma. Pathologic features (presence or absence of PC, mean thickness, continuity, and invasion by tumor) were analyzed. PC thickness was measured using an ocular micrometer to the nearest 1/10mm. A complete PC was found in 77% of clear cell tumors, 74% of papillary, 28% of chromophobe, and 4% of oncocytomas. Tumor PC was present but incomplete in 18% of clear cell, 18% of papillary, 44% of chromophobe, and 56% of oncocytoma. The PC was entirely absent in no clear cell tumors, 6% of papillary, 28% of chromophobe, and 40% of oncocytoma. Mean PC thickness and presence of invasion beyond the PC differed significantly by tumor subtype. Clear cell RCC possessed the thickest PC showing invasion through the capsule in 8% of tumors compared to 30% of papillary tumors. Complete PC invasion was not seen in chromophobe RCC or renal oncocytoma. Oncocytoma and chromophobe RCC characteristically exhibited an incomplete or absent PC. The characteristics of peritumoral PC vary predictably with histologic subtype of renal neoplasms. Clear cell RCC shows the most consistent PC, with a lower rate of invasion beyond it compared to papillary RCC. Chromophobe and oncocytoma characteristically have an incomplete or absent PC

Tumor necrosis adds prognostically significant information to grade in clear cell renal cell carcinoma: A study of 842 consecutive cases from a single institution. Khor LY, Dhakal HP, Jia X, Reynolds JP, McKenney JK, Rini BI, Magi-Galluzzi C, Przybycin CG.Am J Surg Pathol. September 2016;40(9):1224–1231

Tumor necrosis has been shown to be an independent predictor of adverse outcome in renal cell carcinoma. A modification of the International Society of Urological Pathology (ISUP) grading system for renal cell carcinomas has recently been proposed, which incorporates the presence of tumor necrosis into grade. The investigators proposing this system found that necrosis added significant prognostic information to ISUP grade. We attempted to describe our experience with the effect of tumor necrosis in relationship to nuclear grade by reviewing the slides from a large consecutive series of localized clear cell renal cell carcinomas from our institution and obtaining long-term clinical follow-up information (overall survival). Of the 842 clear cell renal cell carcinomas reviewed, 265 (31.5%) were ISUP grade 1 or 2, 437 (51.9%) were ISUP grade 3, and 140 (16.6%) were ISUP grade 4. Tumor necrosis was present in 177 (21%) cases. A total of 547 (64.9%) cases were stage pT1, 83 (9.9%) were stage pT2, 193 (22.9%) were stage pT3a, and 19 (2.3%) were pT3b or higher. Median follow-up was 73.2 months (range: 0.12–273.6), and 310 (36.8%) patients died. On univariable analysis, there was no significant difference in outcome for tumors of ISUP grades 1 to 3. After adjustment for age, tumor stage, and tumor size, ISUP grade 4 and necrosis were significant predictors of overall survival on multivariable analysis. When the recently proposed modified grading system incorporating tumor necrosis was applied to our data, there was no significant difference in overall survival between patients with modified grade 1 tumors and those with modified grade 2 tumors (P = 0.31); however, there was a statistically significant difference between patients with modified grade 1 or 2 tumors and those with modified grade 3 tumors (P = 0.04), and a substantial difference in outcome between those with modified grade 3 and modified grade 4 tumors (P10% necrosis. In conclusion, our study shows that tumor necrosis adds additional prognostic information to ISUP grade and that quantification of necrosis can further stratify patients with ISUP grade 4 tumors

Do clear cell papillary renal cell carcinomas have malignant potential? Diolombi ML, Cheng L, Argani P, Epstein JI.Am J Surg Pathol. December 2015;39(12):1621–1634

There have been no recurrences or metastases of clear cell papillary renal cell carcinoma (CCPRCC) in 268 reported cases with follow-up in the English-language literature. We identified all our cases of CCPRCC (1990–2013), reviewing all cases that preceded the formal designation of the entity. Immunohistochemical stains were performed on 32 cases during their initial workup. In addition, stains for carbonic anhydrase IX and cytokeratin 7 were performed on 2 cases, one with atypical follow-up and the other with a more compact morphology, although not performed initially. An extended panel with AMACR, CD10, and renal cell carcinoma (RCC) was added to the case with atypical follow-up. Fluorescence in situ hybridization for chromosomes 3p, 7, and 17 was performed on the latter case and on another clinically presumed metastatic tumor. In classic cases, immunohistochemical staining was not performed. Fifty-eight patients (31 women; 27 men) with follow-up data were included in our study; 39 cases were from our consult service. The patients׳ ages ranged from 36 to 83 years. Thirty-five patients had cystic or partially cystic lesions; 6 tumors were multifocal, 3 of which were bilateral. The majority (53 patients; 91.4%) presented with stage pT1 disease (size range: 0.2–8cm), 2 patients presented with pT2 disease (8.5 and 10.3cm), 1 patient presented with pT3 disease (6.5cm sarcomatoid RCC focally extending out of the kidney), and pathologic stage was unavailable in 2 cases. Treatment consisted of 29 partial nephrectomies, 26 radical nephrectomies, 2 cryoablations, and 1 cyst ablation. The resection margins were negative in all but one case, with this case disease free after a 26-month period. Two patients had intraoperative tumor disruption and were disease free at 9 and 34 months. Five patients had synchronous ipsilateral renal cell carcinomas (non-CCPRCC). Mean follow-up time was 21 months (range: 1–175 months), with all but 3 patients having no evidence of disease. One patient was presumed to have contralateral disease on the basis of imaging findings and is alive and well 37 months after multiple partial nephrectomies. Metastatic disease to the lung was clinically presumed in 1 patient in whom a higher-grade lesion may have been missed during sampling of the predominantly cystic pT1b tumor and tissue confirmation of the metastases was not obtained. Another case presented with multiple skeletal and pulmonary metastases 8 months after resection of pT3 sarcomatoid CCPRCC. The patient with the sarcomatoid RCC died of multifocal skeletal and pulmonary metastatic disease 13 months after resection of the renal tumor. Our study, the largest to date with follow-up, along with others, suggests that pure CCPRCC is an indolent tumor and should be renamed “clear cell papillary neoplasm of low malignant potential” to reflect their biology