Well-differentiated neuroendocrine tumors (WDNETs) of the pancreas are graded on the basis of mitotic count or Ki67 index. Mitotic count has a narrow cutoff; its assessment is time consuming and carries poor interobserver reproducibility. Phosphohistone H3 (PHH3) is a mitosis-specific marker whose value has been validated in several tumor types. We sought to assess the utility of PHH3 in histologic grading of pancreatic WDNETs. Sixty-three cases of surgically resected primary pancreatic WDNETs were retrieved, and immunohistochemical analysis for PHH3 and Ki67 was performed. Mitotic rate was independently assessed by 4 pathologists on hematoxylin and eosin (HE; in 50 high-power fields [HPFs], expressed as mitoses/10 HPF) and PHH3 stains (in 50 HPFs, one 10×, and one 20× hotspot). PHH3 and Ki67 labeling indices were determined on a single 20× hotspot and expressed as the percentage of positive cells to total cells. We found that mitotic counts by various methods significantly correlated with each other and also with PHH3 and Ki67 indices, with the best correlation seen within the 3 different PHH3 counts (in 50 HPFs, one 10× and one 20× hotspot). Moreover, mitotic count on PHH3 was less time consuming than that on HE (1.68 vs. 3.67 min for 50 HPFs, P<0.0001). Histologic grade determined by PHH3 significantly correlated with disease-specific and disease-free survivals, with the best cutoffs of ≥4 mitoses/10 HPF (2 mm), ≥7 mitoses/10× hotspot, ≥5 mitoses/20× hotspot (log rank test, P<0.0001), and ≥0.16% for PHH3 labeling index (log rank test, P<0.0006). Tumor grades based on PHH3 stain also showed significant correlation with patient survivals in multivariate Cox proportional hazards models (P<0.05). Histologic grades by mitotic counts on PHH3 demonstrated high concordance and κ agreement with grades determined by mitotic count on HE. PHH3 stain also showed improved interobserver agreement in both original mitotic count (intraclass correlation 0.98 vs. 0.79) and final grade assignment (Fleiss κ 0.69 vs. 0.46) as compared with HE. Thus, our data confirmed that histologic grading by PHH3 stain has practical and prognostic values and offers reduced time and improved interobserver reproducibility in mitotic rate assessment and grade assignment. Although larger series are needed for validation, mitotic rate can potentially be determined by counting 1 hotspot, which will greatly facilitate the assessment of histologic grade in pancreatic WDNETs.

Hibernoma arising in the breast is rare and may present as an asymptomatic mass or may be detected by screening mammography. Four histologic types have been identified: typical, myxoid variant, spindle cell variant, and the lipoma-like variant. The most common “typical variant” is composed of pale to eosinophilic multivacuolated cells with interspersed univacuolar cells. Hibernomas are universally benign and are not known to recur or have an aggressive behavior, even in incompletely excised lesions. Hence, their clinical importance lies in distinguishing them from other benign and malignant breast neoplasms as well as inflammatory conditions that come into the histologic or radiologic differential. This review discusses the clinical features, radiologic and histopathologic characteristics, ancillary studies, suggested pathogenesis, differential diagnosis, and treatment of and prognosis for these uncommon lesions.

Nipple-sparing mastectomy (NSM) has recently been increasing in popularity due to a better cosmetic outcome and quality-of-life benefit. The radiologic distance between the tumor and the nipple is independently predictive of nipple-areolar complex involvement and can assist in patient selection for NSM. However, concordance between the preoperative radiologic imaging and histologic evaluation would play a major role in making patient selection for NSM meaningful. We analyzed the pathologic-radiologic correlation for evaluation of retroareolar (RA) margin in NSM. A retrospective histologic and blinded radiologic review of 80 NSM (41 therapeutic and 39 prophylactic) performed on 45 patients was done. Histologically, the cases were divided into positive or close (invasive or in situ carcinoma within 5 mm of the RA margin) and negative (greater than 5 mm from the RA margin). Radiographically, positive cases were defined as suspicious enhancement and/or suspicious findings within 20 mm of the nipple on magnetic resonance imaging (MRI) and/or diagnostic mammography, respectively. Thirty five of 41 (85.4 %) therapeutic cases were concordant. Six cases were discordant, with 2/41 (4.9 %) discordant cases classified as positive at histology, but negative on imaging and 4/41 (9.75 %) discordant cases classified as negative at histology, but positive on imaging. Agreement between pathology and radiology was moderate [kappa coefficient 0.54 (p = 0.0003)].We conclude that there is a significant agreement between histologic and radiologic evaluation for assessment of RA margin and preoperative radiologic imaging; specifically, MRI provides valuable information and should be strongly recommended to help select patients for NSM.

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