Evidence from many studies has established the neoplastic potential of ductal carcinoma in situ, but the origin and the morphological characteristics of the early stages of this proliferation remain unidentified. Workers writing in the early twentieth century observed a cystic transformation of lobules and proposed that it represented one such early stage, and contemporary European and Japanese pathologists have reached the same conclusion. We describe the characteristics of this cystic transformation, which we call us "atypical cystic lobules," and present evidence to support the proposal that the alteration is a step in the formation of low-grade ductal carcinoma in situ. Atypical cystic lobules are a proliferation of luminal cells showing low-grade cytological atypia without architectural atypia. The study group comprised 21 cases of atypical cystic lobules from specimens also showing conventional low-grade ductal carcinoma in situ or lobular neoplasia. Immunohistochemical staining for hormone receptors, keratin 19, and cyclin D1 revealed that atypical cystic lobules demonstrated a consistent immunophenotype, which differs from the pattern shown by normal lobules and benign lesions and matches that of low-grade ductal carcinoma in situ. In about 40% of the cases, atypical cystic lobules merged with fully established micropapillary/cribriform ductal carcinoma in situ. The similarities in the cytological and immunohistochemical features and the proximity of the two types of proliferation suggest that atypical cystic lobules represent an early stage in the formation of certain types of low-grade ductal carcinoma in situ.

The occurrence of endocrine differentiation in some mammary carcinomas seems well-established, but pathologists continue to debate its significance. Contemporary thinking suggests that endocrine tumours of the breast do not constitute a single clinicopathological entity with a consistent histogenesis but rather that endocrine differentiation represents a pathway of neoplastic development available to a range of breast cancers. This pattern of differentiation occurs in tumours with vastly different morphological appearances, such as: ductal carcinoma in situ, mucinous carcinoma, a variant of lobular carcinoma, and low grade invasive ductal carcinoma. Although such tumours share some characteristics with intestinal endocrine neoplasms, the typical pattern of intestinal carcinoid virtually never occurs in mammary lesions. Conventional microscopy permits the diagnosis in most cases. Specialized techniques (histochemistry, immunohistochemistry, and electron microscopy) can serve as the basis for diagnosis in the absence of the appropriate morphological features. Although the system of nomenclature proposed by the World Health Organization for use with endocrine tumours in other organs can be used for endocrine tumours of the breast, only a minority of lesions will fit the established criteria. Most lesions are classifiable in the conventional categories of mammary carcinomas. No special prognostic significance is attached to these tumours at the present time.

We describe two cases of a distinctive in situ and invasive cutaneous adnexal neoplasm occurring in the eyelid. Mucinous carcinoma represented the invasive portion of the tumor in one case, whereas the other infiltrated in small solid nests. The in situ component is identical to the recently described solid papillary carcinoma of the breast (endocrine ductal carcinoma in situ). Both tumors produced intra- and extracellular mucin, exhibited endocrine differentiation by immunohistochemistry and ultrastructural analysis, and were positive for estrogen and progesterone receptors.

Endoscopic bile duct brushing (EBDB) is carried out to differentiate benign from malignant biliary strictures in patients who have pancreaticobiliary disease. The sensitivity of this method for the diagnosis of malignancy is relatively low. The aim of this study is to analyze the cytomorphologic features that are helpful in increasing the sensitivity of detecting these lesions on cytologic samples. These features are compared with slides prepared with the ThinPrep technique. The study included 142 patients with bile duct obstruction or pancreatic mass who underwent EBDB and follow-up surgery or biopsy between 1997 to 2000. Twenty-five (18%) of these cases were positive for malignancy in both EBDB and follow-up surgical biopsy; 20 of these cases were used as positive controls (PC). Sixty-one (43%) were negative in both EBDB and follow-up surgical biopsy specimens, and 21 of those cases were used as negative controls (NC). Fifty-six (39%) cases were negative/atypical in EBDB cytology but were suspicious or positive in the surgical or biopsy specimens (false-negative). We identified the cytologic criteria that were helpful in differentiating our positive and negative control groups and applied these criteria to our false-negative group to see whether our sensitivity could be increased, using well-defined cytologic criteria alone. Of the 56 false-negative cases, 9 (16%) were upgraded to suspicious/positive based on the presence of the following features: three-dimensional (3D) micropapillae (95% PC vs 19% NC, P < 0.0001), anisonucleosis (90% PC vs 5% NC, P < 0.0001), high nuclear-to-cytoplasmic (N/C) ratio (95% PC vs 9% NC, P < 0.0001), nuclear contour irregularity (65% PC vs 24% NC, P = 0.0079), and prominent nucleoli (70% PC vs 38% NC, P = 0.0406). Cytomorphologic features which were not helpful in distinguishing positive and negative cases were: single naked nuclei (50% PC vs 28% NC, P = 0.1597), chromatin granularity (50% PC vs 62% NC, P = 0.54), and necrosis (10% PC vs 5% NC, P = 0.5197). Improvement in diagnostic sensitivity for carcinoma of pancreaticobiliary tract in EBDB samples may be achieved by identifying the key malignant cytomorphologic features: 3D micropapillae, anisonucleosis, nuclear contour irregularity, prominent nucleoli, and high N/C ratio. The sensitivity in detecting malignant biliary strictures increased from 31% to 42% based on these criteria in our current study.