How is atypical papilloma and ductal carcinoma in situ (DCIS) differentiated from benign IDP (L/C ST)?

Updated: Jun 18, 2020
  • Author: Oudai Hassan, MD; Chief Editor: Chandandeep Nagi, MD  more...
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Answer

Answer

The main difficulty in diagnosis lies in differentiating DCIS involving a papilloma from benign IDP (L/C ST) involved by a complex epithelial proliferation with apocrine metaplasia. The apocrine metaplasia causes nuclear enlargement and a uniform increase in cytoplasmic volume, creating the appearance of a monomorphic atypical cellular proliferation. This can closely mimic the appearance of low-grade DCIS.

In benign proliferations (involving an IDP [L/C ST]) that initially contained slit-like spaces, the cytoplasmic expansion brought by apocrine metaplasia may expand these spaces, making them look disturbingly cribriform and further mimicking DCIS. Additionally, the degree to which the epithelium has undergone apocrine metaplasia may differ between cases, with some showing mild partial apocrine metaplasia and others showing classic well-developed apocrine metaplasia.

Cases with early apocrine metaplasia can be particularly problematic, since involved areas may show concerning cellular monomorphism without the reassuring features of unequivocal apocrine metaplasia. In such cases, finding an area that shows transition from a benign proliferation without apocrine metaplasia to a similar proliferation with apocrine metaplasia is a strong indicator the monomorphic proliferation is not DCIS. Similarly, finding an area that shows transition from an area with definite well-developed benign apocrine metaplasia to the monomorphic cellular proliferation of concern is strong evidence that the concerning proliferation is benign.

IDP with prominent apocrine metaplasia. 100x. IDP with prominent apocrine metaplasia. 100x.
Same IDP as above. 200x. The IDP is involved by ex Same IDP as above. 200x. The IDP is involved by extensive, well-developed apocrine metaplasia (volumous pink, granular cytoplasm, enlarged nuclei, and prominent nucleoli). Although the cellular proliferation involving the IDP is monomorphic, the prominent apocrine metaplasia and low grade cytology are strong indicators the proliferation is benign.
Same IDP as above. 200x. A transition from normal Same IDP as above. 200x. A transition from normal (i.e. not involved by apocrine metaplasia) surface epithelium to epithelium that has undergone apocrine metaplasia is present.
IDP sampled by core needle biopsy. 40x. IDP sampled by core needle biopsy. 40x.
Same IDP as above. 200x. A prominent epithelial pr Same IDP as above. 200x. A prominent epithelial proliferation involves the IDP.
IDP. 400x. The proliferation is composed of monomo IDP. 400x. The proliferation is composed of monomorphic cells with abundant pink cytoplasm, that form disturbingly round spaces. These features are concerning, but not sufficient for the diagnosis of DCIS.
Same IDP as above. 200x. In contast to the above p Same IDP as above. 200x. In contast to the above previous figure, this cellular proliferation has typical features of UDH.
Same IDP as above. 200x. A definite focus of UDH w Same IDP as above. 200x. A definite focus of UDH without apocrine metaplasia (black arrow) is seen undergoing a transition to early, poorly-developed apocrine metaplasia (blue arrow). Hyperplasia with moderately-developed apocrine metaplasia (yellow arrow) is seen to transition from the poorly-developed apocrine metaplasia. The focus at the yellow arrow looks very similar to the previous concerning focus. As such, the previously shown concerning focus was interpreted as benign hyperplasia with apocrine metaplasia.
Same IDP as above, blue and black arrows. 400x. Same IDP as above, blue and black arrows. 400x.
Same IDP as above, yellow arrow. 400x. Same IDP as above, yellow arrow. 400x.
IDP with prominent apocrine metaplasia. 100x. IDP with prominent apocrine metaplasia. 100x.
Same IDP as above. 400x. This focus shows a monomo Same IDP as above. 400x. This focus shows a monomorphic proliferation with abundant pink cytoplasm and low grade nuclei. The findings are concerning for DCIS
Same IDP as above. 200x. An area of well-developed Same IDP as above. 200x. An area of well-developed, definite apocrine metaplasia (bottom of figure) is adjacent to an area with features very similar to the cellular proliferation in the IDP that was concerning for DCIS. Given the close proximity of this proliferation to definite, benign apocrine metaplasia, it is most likely the monomorphism of the proliferation is a result of early apocrine metaplasia.
Same IDP as above. 400x. Definite well-developed a Same IDP as above. 400x. Definite well-developed apocrine metaplasia (blue arrow) shows transition from moderately-developed apocrine metaplasia (black arrow). Given this moderately-developed apocrine metaplasia is cytologically indistinguishable from the concerning proliferations in the IDP, we interpreted the concerning proliferations as benign.
IDP sampled by core needle biopsy. 40x. IDP sampled by core needle biopsy. 40x.
Same IDP as above. 200x. This IDP is involved by a Same IDP as above. 200x. This IDP is involved by a small proliferation of epithelial cells, seen on the right side of the figure
Same IDP as above. 400x. The cells comprising the Same IDP as above. 400x. The cells comprising the epithelial proliferation are monomorphic, have a moderate amount of pink cytoplasm, and form somewhat uniform spaces. These features are concerning for DCIS.
Same IDP as above. 200x. This focus shows an area Same IDP as above. 200x. This focus shows an area of well-developed apocrine metaplasia (bottom left), and an adjacent focus of hyperplasia. The hyperplasia has undergone apocrine metaplasia, as made evident by comparison with the adjacent area of well-developed apocrine metaplasia. This focus of hyperplasia has very similar histologic features to the previous described proliferation in this IDP concerning for DCIS. As such, the cellular proliferations in this IDP were interpreted as benign.

In rare cases, low-grade apocrine DCIS involves an IDP (L/C ST). These cases can be difficult to differentiate from IDP (L/C ST). Features favoring apocrine DCIS involving a papilloma over benign IDP (L/C ST) include large size of the apocrine proliferation, lack of transition from a usual ductal hyperplasia (UDH)–like proliferation, lack of transition to a well-developed benign apocrine proliferation, high nuclear grade, nuclear pleomorphism with 3-to-1 difference in nuclear size, and comedo necrosis.

Apocrine DCIS involving an IDP. 20x. Apocrine DCIS involving an IDP. 20x.
Same tumor as above. 40x. A portion of IDP is pres Same tumor as above. 40x. A portion of IDP is present on the left side of the figure. An expansive proliferation is present on the right side of the figure. Necrosis is present.
Same tumor as above. 40x. The proliferation involv Same tumor as above. 40x. The proliferation involves large areas of the lesion.
Same tumor as above. 100x. Extensive necrosis invo Same tumor as above. 100x. Extensive necrosis involves the lesion.
Same tumor as above. 200x. The epithelial prolifer Same tumor as above. 200x. The epithelial proliferation shows no transition from a benign proliferation, and no transition to a well-developed apocrine proliferation. The cells contain abundant pink cytoplasm, as is seen in apocrine DCIS.
Same tumor as above. 400x. The proliferation is co Same tumor as above. 400x. The proliferation is composed of low-grade, monomorphic cells with abundant pink cytoplasm. Convincing polarization of cells is seen (left side of figure).
Same tumor as above. 100x. In this focus, both ben Same tumor as above. 100x. In this focus, both benign IDP (left side of figure) and the atypical cellular proliferation (right side of figure) are seen. No transition from a benign proliferation is present.
Same tumor as above. 200x. Higher power examinatio Same tumor as above. 200x. Higher power examination confirms the lack of transition from a definite benign proliferation, and shows cellular monomorphism.
Same tumor as above. 100x. Foci of comedo necrosis Same tumor as above. 100x. Foci of comedo necrosis are identified.

Papillary DCIS and DCIS involving a papilloma are entirely different lesions. Papillary DCIS consists of a proliferation of papillary processes showing fibrovascular cores. A myoepithelial layer is present at the periphery but no myoepithelial cells lining the fibrovascular cores are present. The presence of a myoepithelial layer lining the fibrovascular cores, which can usually be demonstrated on immunohistochemistry, is a strong indicator that the original lesion is an IDP.

It is important to keep three concepts in mind when evaluating an IDP involved by a suspicious proliferation. First, IDPs (L/C ST) are common, may not require excision, and are frequently involved by complex benign epithelial proliferations. Second, DCIS involving a papilloma likely represents a collision of DCIS with an IDP (L/C ST), and the DCIS component should therefore have morphology identical to common DCIS. Third, apocrine change involving benign epithelial proliferations in IDPs (L/C ST) may mimic DCIS, especially when it is early and poorly developed.

Considering these concepts, monomorphic proliferations that resemble conventional DCIS and show no evidence of apocrine metaplasia should be considered highly suspicious for DCIS involving a papilloma. Conversely, an epithelial proliferation with features of apocrine metaplasia should be diagnosed as DCIS with caution, especially if it shows transition to areas of benign hyperplasia without apocrine metaplasia or areas of benign, well-developed apocrine metaplasia.


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