PNL2: an adjunctive biomarker for renal angiomyolipomas and perivascular epithelioid cell tumours.

AIMS: Renal angiomyolipoma (AML) and perivascular epithelioid cell tumour (PEComa) are members of the microphthalmia-associated transcription factor (MiTF) family of tumours. Traditionally, HMB45 and melan-A have been used to diagnose these lesions; however, low sensitivity can make interpretation difficult. PNL2 is a sensitive and specific biomarker for epithelioid melanoma, and immunoreactivity has also been shown in small series of PEComas. This study was aimed at determining the utility of PNL2 in MiTF and non-MiTF renal tumours. METHODS AND RESULTS: PNL2 immunostaining was performed on 196 tumours, including 40 MiTF renal tumours [AMLs, epithelioid AMLs, sclerosing PEComas, malignant PEComas, and Xp11.2 renal cell carcinomas (RCCs)] and 156 non-MiTF renal tumours. HMB45, melan-A and cathepsin K were also evaluated in a subset of MiTF tumours. Overall, 85% of AMLs and PEComas were positive for PNL2, as compared with 81%, 76% and 95% that were positive for HMB45, melan-A, and cathepsin K, respectively. In 55% of cases, PNL2 stained more extensively than HMB45. PNL2 staining was more frequent than HMB45 (78%) and melan-A (38%) staining in sclerosing and malignant PEComas (89%). All remaining renal tumours, except one melanocytic Xp11.2 RCC, were negative for PNL2. CONCLUSIONS: PNL2 has high sensitivity and specificity for AML and PEComas as compared with non-MiTF renal tumours, and PNL2 appears to be a more useful biomarker for sclerosing and malignant PEComas. For cases that are limited in tissue quantity (i.e. core biopsies) and/or are morphologically suspicious for AML/PEComa, but negative or focally positive for HMB45 and melan-A, PNL2 may be a useful adjunctive biomarker.

IFITM1 Outperforms CD10 in Differentiating Low-grade Endometrial Stromal Sarcomas From Smooth Muscle Neoplasms of the Uterus.

Distinguishing between uterine neoplasms of smooth muscle and endometrial stromal origin is a frequent diagnostic challenge. We investigated the staining pattern of interferon-induced transmembrane protein-1 (IFITM1), a novel endometrial stromal marker, in endometrial and smooth muscle uterine neoplasms and compared it with CD10 in its ability to differentiate between these two groups. Immunohistochemistry for IFITM1 and CD10 was performed in 20 cases of smooth muscle neoplasms (10 cases leiomyoma, 10 cases leiomyosarcoma), 14 cases of endometrial stromal sarcoma (ESS) (12 cases of low grade and 2 cases of high grade) and 12 cases of carcinosarcoma. Staining was scored in terms of intensity and distribution (0=absent, 1=weak/<50%, 2=moderate/50%-75%, 3=strong/>75%). A total score was obtained by adding intensity and distribution scores and classified as positive (score 3-6) or negative (score 0-2). IFITM1 was positive in 10 of 12 (83%) low-grade ESSs, 6 of 20 (30%) smooth muscle tumors (leiomyomas and leiomyosarcomas) and 11 of 12 carcinosarcomas (91.6%). The 2 cases of high-grade ESS were IFITM1 negative. While both IFITM1 (83%) and CD10 (91%) had high sensitivity in differentiating low-grade ESSs from smooth muscle neoplasms, IFITM1 (70%) had higher specificity compared with CD10 (45%). In this study IFITM1 appears to be a more specific marker of endometrial stromal differentiation compared with CD10 in differentiating low-grade ESSs from smooth muscle neoplasms. Thus, IFITM1 may be a valuable tool as part of an immunohistochemical evaluation panel in this diagnostic scenario.

Prostatic ductal adenocarcinoma: An aggressive variant that is underdiagnosed and undersampled on transrectal ultrasound (TRUS)-guided needle biopsy.

INTRODUCTION: We sought to determine if prostatic ductal adenocarcinoma is undersampled and/or underdiagnosed at transrectal ultrasound (TRUS)-guided biopsy. METHODS: With institutional review board approval, we searched our pathology database between 2008 and 2014 for patients with a diagnosis of ≥10% ductal adenocarcinoma on radical prostatectomy and available TRUS-guided needle biopsy specimens. Three blinded genitourinary pathologists independently examined the biopsy slides. The presence or absence of ductal adenocarcinoma was determined. Diagnostic accuracy was calculated using consensus diagnosis as the reference standard. Inter-observer agreement was assessed using Cohen's kappa coefficient. RESULTS: Based on consensus review, 66.7% (12/18) biopsy specimens demonstrated ductal adenocarcinoma and 33.3% (6/18) demonstrated conventional acinar prostatic adenocarcinoma. The sensitivity/specificity for each reader (R) was: 83/100% (R1), 100/83% (R2) and 58/83% (R3) and the inter-observer agreement was only fair (K=0.32). Only two of the original needle-biopsy reports correctly identified ductal adenocarcinoma (sensitivity = 17%). The main limitations of the study are the relatively small sample size and the potential for selection bias since we could only examine patients who underwent radical prostatectomy. CONCLUSIONS: Prostatic ductal adenocarcinoma may be undersampled at TRUS-guided biopsy and in this study was under-reported in routine clinical practice. This highlights the importance of increased awareness of ductal adeoncarcinoma and the need for clear diagnostic criteria. These findings have significant clinical impact especially when determining candidacy for active surveillance protocols.

Multi-parametric (mp) MRI of prostatic ductal adenocarcinoma.

BACKGROUND: Prostatic ductal adenocarcinoma (DCa) is an aggressive variant of conventional adenocarcinoma (CCa) with mixed DCa and CCa tumors comprising up to 5% of all prostate cancers. DCa may be underestimated on T2-weighted (T2W) MRI. This study assessed the mp-MRI appearance of DCa as compared with CCa. METHODS: With research ethics board approval, we identified 38 patients who underwent mp-MRI (T2W, DWI, and DCE) and radical prostatectomy (RP) between 2012 and 2014. Eight DCa in 8 patients and 39 CCa tumor foci in 30 consecutive patients were identified. Tumor volume, apparent diffusion coefficient (ADC;10(-3) mm(2) /s), and time-signal intensity (SI) curves were calculated. Parametric data were compared using the Kruskal-Wallis test and univariate regression. Time-SI curves were compared using the chi-square test. RESULTS: Tumor volumes were: 1.62(±1.02) for DCa, 1.03(±0.54) for Gleason 9, 0.88(±0.93) for Gleason 7/8, and 0.26(±0.14) mL for Gleason 6. There was no difference in size between DCa and Gleason 9 (P = 0.22); however, DCa were larger than Gleason 7/8 (P = 0.03) and Gleason 6 (P = 0.003) tumors. ADC values were: 0.789(±0.22) for DCa, 1.01(±0.19) for Gleason 9, 0.992(±0.23) for Gleason 7/8 and 1.389(±0.41) 10(-3) mm(2) /s for Gleason 6 tumors. There was no difference in ADC between DCa and Gleason 9 (P = 0.14) or Gleason 7/8 (P = 0.055) tumors. There was a difference in ADC for DCa and Gleason ≥7 CCa compared to Gleason 6 tumors, (P < 0.001 and P = 0.012). All DCa demonstrated type III time-SI curves. Gleason ≥ 7 tumors demonstrated type II/III curves. Gleason 6 tumors demonstrated Type I/II time-SI curves. There was no difference in curve type between groups, (P = 0.18). CONCLUSION: Although DCa mimics Gleason score 3 + 3 = 6 tumor at T2W MRI; DCa resembles Gleason ≥7 CCa on mp-MRI.

Prostatic ductal adenocarcinoma: an aggressive tumour variant unrecognized on T2 weighted magnetic resonance imaging (MRI).

INTRODUCTION: Prostatic ductal adenocarcinoma (DCa) is an aggressive variant. The purpose of this study was to determine if T2 signal intensity (SI) differs from conventional adenocarcinoma (CCa). MATERIALS AND METHODS: A retrospective study of patients who underwent preoperative MRI and prostatectomy between 2009 and 2012 was performed. T2 SI ratios (SIR) for tumour (T) to obturator internus muscle (M) and normal peripheral zone (PZ) were compared. Two radiologists evaluated the central gland/PZ to detect tumours and compared diagnostic accuracy. RESULTS: T2 SIR for DCa were 3.60 (T/M), 0.66 (T/PZ); 2.68 (T/M), 0.47 (T/PZ) for Gleason 9; 2.50 (T/M), 0.47 (T/PZ) for Gleason 7/8 and 3.95 (T/M), 0.73 (T/PZ) for Gleason 6 tumours. There was a difference in T2 T/M and T/PZ SIR between DCa and Gleason 9 (p = 0.003, p = 0.004) and Gleason 7/8 (p = 0.006, p = 0.002), but no difference in SIR between DCa and Gleason 6 tumours. The sensitivity for tumour detection was 0-27 % for DCa, 64-82 % for Gleason 9, 44-88 % for Gleason 7-8 and 0-20 % for Gleason 6. There was a difference in the sensitivity of detecting Gleason 9 and 7/8 tumours when compared to DCa (p = 0.004, p = 0.001). CONCLUSIONS: DCa resembles Gleason score 6 tumour at T2-weighted MRI, which underestimates tumour grade and renders the tumour occult. KEY POINTS: Prostatic ductal adenocarcinoma is aggressive, resembling endometrial carcinoma at histopathology. Prostatic ductal adenocarcinoma resembles Gleason score 6 tumour at T2-weighted MRI. MRI grading may underestimate ductal adenocarcinoma based on increased T2 signal.

Topographic Distribution of Papillary Thyroid Carcinoma by Mapping in Coronal Sections of 125 Consecutive Thyroidectomy Specimens.

INTRODUCTION: Mapping of different foci in multifocal papillary thyroid carcinoma (PTC) has previously not been done as it is difficult to do so when thyroid specimens are serially sectioned transversely (ie, parallel to the horizontal plane). In this study, thyroidectomy specimens were serially sectioned coronally (ie, parallel to the largest surface of the thyroid gland), which allows for panoramic and 3-dimensional visualization of PTC foci and their relationship to one another. MATERIALS AND METHODS: A total of 125 consecutive total thyroidectomies or lobectomies followed by completion thyroidectomies were serially sectioned coronally and reviewed with identification and characterization of PTC foci. PTCs were grouped into either discrete, encapsulated nodule(s) (EN) of both follicular or papillary architecture, usual variant (UV), or tall cell variant (TCV). RESULTS: The predominant tumor masses were identified in the right lobe, isthmus, and left lobe in 52%, 8%, and 40%, respectively. The largest tumor nodules ranged from 3 to 60 mm (18.8 ± 6.6) with the UV, EN, and TCV groups accounting for 58%, 24%, and 18% of cases, respectively. Three topographic patterns of PTC can be distinguished as follows: (a) single tumor nodule (37 cases), (b) main tumor nodule with satellite nodule(s) displaying no or varying degrees of fusion with the main one (30 cases), and (c) main tumor nodule with either a second large nodule or randomly occurring tumor nodules (58 cases). Bilaterality can be seen in all 3 patterns but was most prevalent in the group comprising the main tumor nodule with either a second large nodule or random tumor nodules. It was least frequent in the EN group without random tumor nodules. The difference in rates of bilaterality between tumors <10 mm and ≥10 mm was statistically significant (P < .01). For all 3 groups, satellite nodules displayed histopathological features that were similar or dissimilar to the main tumor mass. They may be of a different variant than that of the main tumor nodule. CONCLUSIONS: With panaromic and 3-dimensional visualization, individual tumors/satellite or random nodules of multifocal PTC were readily identified in serial coronal sections of thyroidectomy specimens. Bilaterality was frequently observed in tumors associated with random PTC foci, whereas, the EN group tended to be unilateral and was not associated with random foci.