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Aims: Phosphohistone H3 (PhH3) has been proposed as a novel proliferation marker in breast cancer. This study compares the interobserver agreement for assessment of the mitotic activity index (MAI), Ki67 expression, and PhH3 in a cohort of oestrogen receptor (ER)-positive breast cancer patients., Methods and Results: Tumour samples of 159 luminal breast cancer patients were collected. MAI and PhH3 scores were assessed by three breast cancer pathologists. Ki67 scores were assessed separately by two of the three pathologists. PhH3-positive cells were counted in an area of 2 mm 2 , with a threshold of ≥13 positive cells being used to discriminate between low-proliferative and high-proliferative tumours. Ki67 expression was assessed with the global scoring method. Ki67 percentages of <20% were considered to be low. The intraclass correlation coefficient (ICC) and Cohen's κ statistics were used to evaluate interobserver agreement. The impact on histological grading of replacing the MAI with PhH3 was assessed. Counting PhH3-positive cells was highly reproducible among all three observers (ICC of 0.86). The κ scores for the categorical PhH3 count (κ = 0.78, κ = 0.68, and κ = 0.80) reflected substantial agreement among all observers, whereas agreement for the MAI (κ = 0.38, κ = 0.52, and κ = 0.26) and Ki67 (κ = 0.55) was fair to moderate. When PhH3 was used to determine the histological grade, agreement in grading increased (PhH3, κ = 0.52, κ = 0.48, and κ = 0.52; MAI, κ = 0.43, κ = 0.35, and κ = 0.32), and the proportion of grade III tumours increased (14%, 18%, and 27%)., Conclusion: PhH3 seems to outperform Ki67 and the MAI as a reproducible means to measure tumour proliferation in luminal-type breast cancer. Variation in the assessment of histological grade might be reduced by using PhH3, but would result in an increase in the proportion of high-grade cancers., (© 2020 The Authors. Histopathology published by John Wiley & Sons Ltd.)

Aims: Unusual cytoplasmic alterations have recently been reported in poorly differentiated cutaneous angiosarcoma, making an accurate diagnosis challenging. As these tumours remain poorly documented, we aimed to study their clinicopathological characteristics more comprehensively., Methods and Results: Six cutaneous angiosarcomas with unusual cytoplasmic alterations were identified from referral files. All tumours arose as nodules or plaques (range: 05-195 mm) on sun-damaged skin of the head and neck of elderly males (median age: 76.5 years). Histologically, the tumours were composed of enlarged epithelioid cells showing prominent signet ring (n = 3), foam (n = 2) or granular cell (n = 1) change. Vasoformative elements were only focally noted. By immunohistochemistry, all tumours expressed CD31 and avian v-ets erythroblastosis virus E26 oncogene homologue (ERG). Foam cell change was associated with additional expression of CD68 and CD163. Follow-up (median: 8 months) showed death from disease (n = 1), death from a gastrointestinal bleed (n = 1), and a cutaneous metastasis (n = 1). Only two patients are alive with no evidence of disease., Conclusions: Our findings outline the morphological spectrum of cytoplasmic change in cutaneous angiosarcoma. Awareness and a high degree of suspicion in the context of tumours affecting sun-damaged skin of the elderly are necessary to direct appropriate immunohistochemical work-up with inclusion of the endothelial cell markers CD31 and ERG., (© 2014 John Wiley & Sons Ltd.)

Thirteen cases of nasal lymphomas with T-cell or natural killer (NK)-cell phenotype were studied, with attention to clinical presentation and follow-up, the presence of Epstein-Barr virus (EBV) using in situ hybridization (EBER), the immunophenotype, and the presence of cytotoxic granules. All but two patients presented with stage I disease. In three cases local progression resulted in involvement of the central nervous system. When dissemination occurred, this was predominantly to extranodal localizations, in two cases to the skin. Response to therapy was highly variable, but patients treated with radiotherapy with or without additional chemotherapy had a better prognosis than patients treated with initial chemotherapy alone. All lymphomas were associated with EBV, and most cases showed cytotoxic features, ten of which were CD56 positive. In eight cases a T-cell origin was proven, but in five cases a possible NK-cell origin could not be excluded. No clinical differences were seen between true T-cell lymphomas and possible NK-cell neoplasms. Nasal T-cell lymphomas should be considered as a distinct clinicopathological entity, strongly associated with EBV, and with cytotoxic features in most cases. No prognostic parameters were detected to predict dissemination and response to therapy.

Infantile myofibromatosis, congenital fibrosarcoma and congenital/infantile haemangiopericytoma are generally considered distinct entities. Overlapping microscopic features between infantile myofibromatosis and congenital fibrosarcoma, and between infantile myofibromatosis and congenital/infantile haemangiopericytoma, however, have been noted, but not formally reported. This report concerns six neonatal tumours, each exhibiting more than one of the above patterns, supporting a histogenetic relationship among these entities. Immunohistochemistry for smooth muscle actin was found to be useful in the diagnosis of congenital/infantile haemangiopericytoma, and also served to support a histogenetic relationship with the other two entities under consideration.