Metastatic potential to regional lymph nodes with Gleason score ≤7, including tertiary pattern 5, at radical prostatectomy.

OBJECTIVES: To determine the risk of pelvic lymph node (LN) metastases at radical prostatectomy (RP) for Gleason score (GS) ≤7: 3 + 3 = 6 (grade group [GG]1); 3 + 4 = 7 (GG2); 3 + 4 = 7 (GG2) with tertiary pattern 5 (T5); 4 + 3 = 7 (GG3); 4 + 3 = 7 (GG3) with T5, using the 2014 modified Gleason grading system and the novel GG system. MATERIALS AND METHODS: We searched our RP database to indentify cases of GS ≤7 prostate cancer with simultaneous pelvic LN dissection (PLND) in the period between 2005 and 2014. Since 2005, we have graded all glomeruloid and cribriform cancer as Gleason pattern 4 and have graded mucinous adenocarcinoma based on the underlying architectural pattern, consistent with the 2014 modified Gleason grading system. All RPs were embedded in entirety, including the PLND. A total of 7 442 cases were identified, of which 73 had at least one positive LN (+LN). RESULTS: The incidence rates for regional LN metastases at RP for 3 + 3 = 6 (GG1), 3 + 4 = 7 (GG2), 3 + 4 = 7 (GG2) with T5, 4 + 3 = 7 (GG3) and 4 + 3 = 7 (GG3) with T5 were 0, 0.6, 0.4, 4.3 and 6.3%, respectively. There was a statistically significant difference in risk of +LNs at RP between the grade groups, as defined by the novel GG system. There was no statistically significant difference in risk of +LNs at RP for men with 3 + 4 (GG2) vs 3 + 4 (GG2) with T5 and for men with 4 + 3 (GG3) vs 4 + 3 (GG3) with T5. Non-pelvic LN involvement was identified in 0.2% of all RP cases. Two patients with GS 3 + 4 = 7 with <5% pattern 4 experienced LN metastases. CONCLUSION: This study supports our previous finding that men with GS 6 (GG1) at RP have no risk of LN metastases. These findings also support the 2014 revisions to the Gleason grading system where 3 + 3 with T4 (2005 modified grading system) is now considered 3 + 4 (GG2), with a comment on percent pattern 4, because <5% pattern 4 increases the risk of LN metastases. It also supports keeping 3 + 4 (GG2) with T5 (<5% pattern 5) and 4 + 3 (GG3) with T5 with their respective grade groups, with a notation of T5 because the <5% higher grade component did not increase the risk of LN metastases within a given GG. Our findings highlight that 3 + 4 (GG2) and 4 + 3 (GG3), even with a 5% higher grade component, are distinct groups with respect to LN metastases and should not be combined under the umbrella designation of GS 7 as is often the case in the literature with the Gleason grading system.

Diagnostic dilemmas in enlarged and diffusely hemorrhagic adrenal glands.

We have noted an increasing number of cases of enlarged adrenal glands where the underlying diagnosis was masked by a diffusely hemorrhagic process. We identified from our database 59 cases (32 consults, 27 routine) of adrenal glands with diffuse (>25%) hemorrhage received between 2000 and 2014. Fifty-three adrenalectomies and 6 biopsies were identified. The diagnoses after central review were 41 adrenocortical adenomas, 1 nodular adrenocortical hyperplasia with associated myelolipoma, 1 benign adrenocortical cyst, and 10 nonneoplastic adrenal glands with hemorrhage. A definitive diagnosis for the 6 biopsies was precluded by the sample size. The adrenocortical adenomas (size, 1-13 cm; 25%-95% hemorrhage) showed clear cell change in the neoplastic area (10%-80% of the tumor), 19 showed focal calcification (1 with ossification), 11 showed areas of papillary endothelial hyperplasia, 10 showed scattered lymphoplasmacytic inflammation, 6 showed benign cortical tissue extending beyond the adrenal capsule into soft tissue, 1 showed necrosis in the form of ghost cells, 2 showed lipomatous change, and 6 were associated with incidental benign lesions (1 cortical cyst, 1 schwannoma, and 4 myelolipomas). Twenty-four of the adrenocortical adenomas were consults where the referring pathologist had trouble classifying the lesion. Of the 10 nonneoplastic adrenals (4.5-22 cm; 40%-80% hemorrhage), 2 were consults. In summary, pathologists have difficulties recognizing adrenocortical adenomas in the setting of a massively enlarged and hemorrhagic adrenal gland. Although there is a correlation between adrenocortical malignancy and size, hemorrhage into nonmalignant adrenal glands can result in markedly enlarged adrenals.

Benign and Malignant Brenner Tumors Show an Absence of TERT Promoter Mutations That Are Commonly Present in Urothelial Carcinoma.

Brenner tumors are uncommon ovarian neoplasms, which have morphologic and immunophenotypical features of transitional cell (urothelial) differentiation. The origin of Brenner tumors is perplexing, but they are believed to arise from transitional cell metaplasia occurring within the ovary and/or fallopian tube, although it is controversial whether this metaplasia is truly along transitional cell lines. Recently, TERT promoter mutations have been identified in urothelial carcinoma (UC) with high frequency (approximately 70%), and the current literature suggests a potential diagnostic and/or prognostic role of these mutations in UC. Molecular evidence supporting that Brenner tumors represent neoplasms exhibiting transitional cell differentiation is scant. To explore this further, we investigated a series of 19 Brenner tumors of the ovary (15 benign and 4 malignant) for the presence of TERT promoter mutations after genomic DNA extraction from formalin-fixed paraffin-embedded tissue blocks and standard polymerase chain reaction sequencing. TERT promoter mutations were not identified in any of the cases (0/19). The absence of TERT promoter mutations in Brenner tumors suggests that despite the morphologic and some immunophenotypical resemblance to non-neoplastic and neoplastic transitional epithelium, Brenner tumors may exhibit a molecularly distinct pathogenesis. The findings also may portend diagnostic utility in rare cases wherein it is difficult to distinguish a primary malignant Brenner tumor of the ovary from metastatic UC.

Do Clear Cell Papillary Renal Cell Carcinomas Have Malignant Potential?

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 to 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 to 8 cm), 2 patients presented with pT2 disease (8.5 and 10.3 cm), 1 patient presented with pT3 disease (6.5 cm 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 to 175 mo), 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.