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Childhood Interstitial lung disease (chILD) is an umbrella term used to define a broad range of rare, diffuse pulmonary disorders with altered interstitial structure that leads to abnormal gas exchange. Presentation of chILD in infancy can be difficult to differentiate from other common causes of diffuse lung disease. This article aimed at paediatricians provides an overview of interstitial lung disease presenting in infancy and includes key clinical features, a suggested approach to investigation and a summary of management. An overview of three clinical cases has been included to demonstrate the diagnostic approach, characteristic investigation findings and varied clinical outcomes.

Rates of large breast cancers should decrease in a population that is offered mammography screening, but women continue to present with them. We sought an explanation in a population-based epidemiological study of 1,459 women diagnosed with invasive breast cancer in 2002-2003 in Australia; breast cancers wereor =2 cm in 766 women (53%) and 11-1.9 cm in a comparison group (693, 47%). We interviewed the women about their personal, mammogram and breast histories in the years before diagnosis and collected biological characteristics of tumors and mammogram dates from medical records. The strongest correlate of breast cancer size at diagnosis was the method of detection: the odds of aor =2 cm breast cancer was substantially lower for detection by a screening mammogram (OR = 0.27, 95% CI 0.21-0.34; p0.001) than for detection after a breast symptom. Higher BMI (ORs approximately 1.6 foror =25 kg/m(2)), higher cancer grade (ORs of 1.6 for moderate, 2.89 for high grade) and lobular type (OR 2.09, 95% CI 1.45-3.0) were also independent correlates (p0.001) of aor =2 cm breast cancer. HRT use strongly reduced the odds but only in cancers detected after a breast symptom (OR = 0.49, 95% CI 0.33-0.74; p = 0.002), not in those detected by a screening mammogram. As assessed from their proportional contribution toor =2 cm breast cancers in our study population, lack of mammogram detection, BMIor =25 kg/m(2) and moderate or high grade of the cancer were the most important factors with population attributable fractions of 42%, 11% and 29% respectively; the first 2 are amenable to intervention.

BACKGROUND Women with breast carcinoma diagnosed before age 40 years have a greater prevalence of germline BRCA1 and BRCA2 mutations than women with breast carcinoma diagnosed at older ages. Several recognizable histologic characteristics have been identified in breast carcinoma from studies of BRCA1/2 mutation carriers who belong to multiple-case families. The authors attempted to determine whether breast carcinoma occurring before age 40 years in BRCA1 or BRCA2 mutation carriers who were not selected for family history could be distinguished histologically from one another and from breast carcinoma in women of a similar age without a germline BRCA1 or BRCA2 mutation. METHODS The study undertook a histologic assessment of breast carcinomas diagnosed before age 40 years identified from a population-based study. RESULTS Breast carcinoma in BRCA1 mutation carriers was associated with a distinct histologic appearance; these tumors were high grade, and had exceptionally high mean mitotic counts, a syncytial growth pattern, pushing margins, and confluent necrosis. Atypical medullary carcinoma was overrepresented in BRCA1 mutation carriers. All low grade tumors and tumors with low mitotic rates belonged to the group without BRCA1 or BRCA2 mutations. Pleomorphic lobular carcinomas and extensive intraduct carcinomas were more common in BRCA2 mutation carriers. CONCLUSIONS Breast carcinoma occurring in women with a germline BRCA1 or BRCA2 mutation have recognizable histologic phenotypes, which may be useful in identifying individuals more likely to carry germline mutations. Histologic examination of breast carcinoma should become an important part of the evaluation of women seeking genetic testing for germline mutations in these breast carcinoma susceptibility genes. [See editorial on pages 2251-4, this issue.] Cancer 1998;83:2335-2345. © 1998 American Cancer Society.

pression, whereas the other contained two clonal populations and was controlled only after treatment with antineoplastic chemotherapy. Conclusion. This study has demonstrated two cases of PTLPD that were derived from donor lymphoid tissue. Although both cases were associated with EBV and remained localized to allograft tissue, their clonality and response to therapy differed. Cancer 1994;74:2436-41.

Background: DCIS represents preinvasive malignant change. With screening mammography DCIS has become a common entity. Its natural history is poorly understood and treatment remains controversial. Using a retrospective population based cohort, we have identified histological and molecular variables predictive of recurrence. Methods: All cases of DCIS reported in Victoria between 1988 and 1992 were entered into the Victorian Cancer Registry. In Situ and Small Cancer Register (ISSIBCR) and followed up annually regarding treatment, the event of recurrence and its nature and location. From this register a cohort of 66 DCIS lesions with subsequent recurrence as in situ or invasive disease were studied histologically, immunohistochemically and with CGH-based genetic analyses comparing them to a nested randomized control group of DCIS without recurrence matched for patient age and year of diagnosis. Recurrences have been analysed by the same techniques to compare them to the primary lesion. Results: 13 histological features were evaluated and lesion size, nuclear pleomorphism, cellular polarity, micropapillary architecture and central necrosis were all significant predictors of recurrence (p < 0.05). Immunohistochemistry showed p21 overexpression, bcl2 negativity and ERBB2 positivity to be markers of recurrence. In the case of ERBB2, positivity was a predictor of recurrence even when its overexpression was focal. Primary and recurrent DCIS lesions had similar morphological appearances, and grade of primary DCIS correlated with grade of subsequent invasive cancer. This morphological similarity was paralleled by similar protein expression and genomic changes in both in situ and invasive recurrences. Conclusion: We have identified histological and immunohistochemical markers of recurrence in DCIS, and shown similarities in morphology, protein expression and genetic changes between primary DCIS and its recurrence.