Ductal Carcinoma In Situ, Solid and Cribriform Pattern Dr. Jean F. Simpson

A 58 year old woman underwent a stereotactic needle biopsy after suspicious calcifications were identified on a screening mammogram. She had no previous history of abnormal mammograms. Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Microscopic appearance The section shows several cores of breast tissue that contain a proliferation of monomorphic cells filling and expanding lobular units, and true ducts. Individual cells have round, regular nuclei with inconspicuous nucleoli, and homogenous pale cytoplasm. The cells are arranged into microglandular structures or rosettes, some of which are subtle. In areas where the micro-rosette lumina are not evident, the cells appear to be overlapping, and not evenly placed. Some of the spaces have punctate necrosis and associated microcalcification. The overall size of the lesion based on the microscope slide is 6 mm. Differential diagnosis Florid hyperplasia without atypia Atypical ductal hyperplasia Ductal carcinoma in situ, solid and cribriform pattern, low grade, with focal necrosis Lobular carcinoma in situ The distinction of atypical ductal hyperplasia and low grade ductal carcinoma in situ (DCIS) is based on the extent of the lesion. Both of these entities are characterised by a uniform, monomorphic population of cells. In this example, the extent of the lesion (6 mm) is sufficient to qualify as DCIS. Moreover, the involvement of several adjacent lobular units in continuity with true ducts cements the diagnosis of DCIS. In areas where the lumens of the rosettes are not evident, the back-to-back arrangement of the rosettes can be mistaken for the pattern of cellular overlap that is defining for florid hyperplasia without atypia. Another diagnostic consideration is lobular neoplasia, but careful scrutiny will identify distinct cell borders and the formation of microglandular structures. Immunohistochemical studies were not felt to be necessary, but this example of DCIS would be expected to express E-cadherin. Follow up An image-guided wire localisation biopsy was performed. The previous biopsy site was identified, and no residual lesion was present. The patient underwent brachytherapy. Final Diagnosis Ductal carcinoma in situ, solid and cribriform pattern, low grade with punctate necrosis, and determinant calcifications, 6 mm. Discussion and Clinical Implications There is a wide recent acceptance of the heterogeneity of DCIS. [1, 2, 3] Furthermore, many accept that cytology and histologic pattern (Table 1) can be used together to make assignment into categories more precise, reproducible, and clinically useful. TABLE 1 Histology Cytology Necrosis Calcification Comedo* High grade Extensive Linear, branched Intermediate Intermediate Limited Focal, punctate Non-comedo    Cribriform    Solid    Micropapillary# Low grade Absent Microscopic foci * Although different terms are used for this high-grade category, the presence of both advanced nuclear atypia and extensive necrosis are necessary criteria. # Some of these are high grade and may be considered comedo type. When present in pure form, they may be extensive. It is evident that the lower grade, non-comedo lesions are likely to be smaller and also may be amenable to treatment with very low recurrence rates (Table 2). TABLE 2 Study Follow-up (mo) Recurrence rate (high grade/ comedo) (%) Recurrence rate (low-intermediate grade/ non-comedo) (%) Lagios 100 11/36 (30.5) 1/42* Bellamy 60 10/25 (40) 0/6 (0) Ottesen 63 23/76 (30.6) 3/36 (8.3) Schwartz 47 10/21 (47.6) 1/51 (2) * The single recurrence was from a patient whose biopsy contained intermediate-grade DCIS, no low-grade DCIS cases recurred. Several studies have assessed the risk of subsequent invasive carcinoma for patients in whom the diagnosis of DCIS was not made at the initial biopsy for small, non-comedo lesions. Approximately one third of these patients developed invasive breast cancer in the same region of the same breast within 10–18 years. Thus, it would appear that small examples of non-comedo DCIS are non-obligate precursor lesions. If one accepts the fact that some of the lesions in the 1978 [4] and 1982 [5] articles were completely removed, it is likely that the progression rate of non-comedo DCIS to invasive cancer over a prolonged period of time approaches 50%. Developing evidence strongly supports the idea that adequate excision of DCIS lesions without radiotherapy (Table 2) may lead to cure. [6] Smaller non-comedo examples of DCIS are regularly treated successfully at least with follow-up extending to 7 or 8 years. [7, 8, 9, 10] Role of radiation What is the role of radiotherapy in reducing local recurrence after wide excision of a localised area of DCIS? Preliminary data (with follow-up of <4 years) from a study in the United States [11] suggests that radiotherapy may reduce the rate of disease recurrence within the breast following an adequate excision of a localised area of DCIS. It is not clear from this study whether the benefits of radiotherapy relate to all types of DCIS or whether the benefits will be demonstrable beyond 43 months of follow-up. To determine the optimum treatment for DCIS detected in screening programs, a number of clinical trials are underway. It is widely accepted that the mammographically detected DCIS lesion should be considered separately from the regularly larger lesions presenting with palpable masses and nipple discharge. [12] Complete embedding of the lesion with accounting for the three-dimensional extent of the disease within the breast is critical for conservative treatment of DCIS. Almost any case of DCIS excised with a 1 cm margin should not recur locally. [13] What has not been established is that all cases of DCIS that are amenable to local excision for cure require a 1 cm margin. An Eastern Oncology Cooperative Group Trial (ECOG 5194) is currently accruing patients to determine which DCIS lesions may be cured by local excision alone. Entry criteria include complete submission of the lesion by sequential sectioning, margins clear of DCIS by at least 3 mm, and size of the DCIS <=1 cm for high-grade and <=2.5 cm for intermediate- or low-grade DCIS. Patients are accepted into this trial after central review of their slides. In summary, there is strong evidence that small size and low histologic grade interact to produce lesions easily cured by local excision without radiation therapy. This is certainly true of lesions that are <1 cm in largest diameter. Thus, the best estimate of size of a DCIS lesion should be stated even for core biopsy specimens to facilitate clinical management. The greatest extent of a lesion is assessed most easily by careful pathologic–mammographic correlation, which is mandatory in most instances. It is also clear that extensive high-grade, comedo lesions are not easily cured and that recurrences are common even after radiation therapy. [14] Precisely which concurrence of histologic grade, size, and margin clearance is to be the determinant of therapeutic decision-making is an area under investigation currently. However, it should be understood that local recurrence in the setting of a low-grade lesion is very unlikely to be a life-threatening event and that a woman's desire for breast conservation with a willingness to accept the possibility of local recurrence may be as important with regard to therapeutic decision-making as any other consideration. In contrast, local recurrence in the setting of a high-grade DCIS lesion is much more likely to be associated with invasion, high-grade histology, and distant metastases. 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