Tumor factors predictive of response to hypofractionated radiotherapy in a randomized trial following breast conserving therapy.

PURPOSE: To determine whether tumor grade, molecular subtype and hypoxia predict response to hypofractionated versus standard radiotherapy (RT) following breast-conserving surgery (BCS) for node-negative breast cancer in a randomized controlled trial (RCT). PATIENTS AND METHODS: Formalin-fixed paraffin-embedded (FFPE) tumor blocks were available on 989 of 1234 patients enrolled in the Hypofractionation Whole Breast Irradiation (HWBI) Trial. A central pathology review and assessment of tumor grade using the Nottingham grading system was carried out. Tumors were classified by molecular subtype as luminal A, luminal B, HER2 enriched, basal-like or unclassified using a six-biomarker panel; ER, PR, HER-2, Ki67, CK5/6 and EGFR. Tumors were also classified as hypoxic based on the expression of HIF1α, CAIX or GLUT-1. The primary end point was local recurrence (LR). RESULTS: Median follow-up was 12 years. In the multivariable Cox model, molecular subtype was the only factor predictive of LR, the 10-year cumulative incidence was 4.5% for luminal A and basal-like, 7.9% for luminal B and 16.9% for HER-2 enriched tumors (P < 0.01). Tumor grade, molecular subtype or hypoxia did not predict response to hypofractionation. CONCLUSIONS: In women enrolled in the HWBI trial following BCS tumor molecular subtype predicted LR. However tumor grade, molecular subtype and hypoxia did not predict response to hypofractionation suggesting that patients with node-negative breast tumors of all grades and molecular subtypes may be safely treated with hypofractionated RT regimens.

The spectrum of apocrine lesions of the breast.

Apocrine change is seen in a wide spectrum of breast lesions, ranging from microscopic cysts to invasive carcinoma. This article reviews the range of apocrine lesions and discusses the clinical significance of these lesions. Although apocrine change in many cases does not present any diagnostic difficulty, apocrine proliferations demonstrating cytologic atypia can be particularly challenging. The histologic criteria that have been proposed to foster reproducibility in categorizing such lesions are reviewed. This review attempts to clarify the terminology that has been applied to a range of benign lesions, including sclerosing adenosis and complex sclerosing lesions, containing foci of apocrine change. Malignant apocrine lesions, including both in situ and invasive carcinoma, are also discussed.

Massive perivillous fibrinoid causing recurrent placental failure.

OBJECTIVE: To establish the incidence, recurrence rate and consequences of massive perivillous fibrinoid. DESIGN: Retrospective analysis of the histology of all placentas with a diagnosis of massive perivillous fibrinoid between 1991 and 1998, together with the maternal case records. SETTING: The histopathology department of the Rotunda Hospital, Dublin, Ireland. POPULATION: A relatively homogeneous group of pregnant women in the northern part of Dublin City, which is the catchment area for the Rotunda Hospital, delivered between 1991 and 1998. METHODS: Retrospective review of archival placental pathology and maternal charts. MAIN OUTCOME MEASURES: The incidence of massive perivillous fibrinoid, perinatal outcome and recurrence rate. RESULTS: The incidence of massive perivillous fibrinoid was 0.028%, with a recurrence rate of approximately 18%. All the infants suffered intrauterine growth restriction; there was a 31% fetal loss rate and a 33% preterm delivery rate. CONCLUSIONS: Massive perivillous fibrinoid is associated with intrauterine death, intrauterine growth restriction and preterm delivery. It has a significant recurrence rate and both the clinical findings of intrauterine growth restriction and the postmortem findings imply a syndrome of chronic placental insufficiency.

Chronic myelomonocytic leukemia revealed by uncontrollable hematuria.

Nephrectomy was performed for uncontrollable unilateral hematuria in an apparently healthy 72-year-old man. The suburothelial connective tissue of the kidney was infiltrated by primitive myeloid cells with associated acute vasculitis and foci of extramedullary hematopoiesis. Subsequently, the patient was shown to have chronic myelomonocytic leukemia. Although renal involvement and vasculitis have been recorded previously in chronic myelomonocytic leukemia, this is the first occasion, to our knowledge, where their concurrence resulted in such a spectacular presentation.