Metastatic “Ductal Carcinoma In Situ–Like” Lobular Carcinoma in a Lymph Node: A Case Report and Review of the Literature

Introduction

Metastatic invasive ductal carcinoma simulating various morphological forms of ductal carcinoma in situ (DCIS) in the lymph nodes has been described in the literature.^1-8 Recent reports have also shown lobular carcinoma in situ with comedo-type necrosis mimicking DCIS. ⁹

Case Report

A 52-year-old female presented with 2 lesions in the left breast on mammography, and a mastectomy with axillary lymph node dissection was performed. Gross pathological examination showed a 3.5 × 2.5 × 1.0 cm indistinct tumor in the lower outer quadrant and a 2.5 × 2.5 × 1.8 cm circumscribed tumor in the upper outer quadrant. Microscopic assessment of the tumor in the lower outer quadrant revealed an invasive pleomorphic lobular carcinoma (PLC) and immunohistochemical analysis showed no expression of E-cadherin (Figure 1A and B). Sixteen of 17 axillary lymph nodes showed metastatic lobular carcinoma with foci of solid and comedo-type DCIS-like features (Figure 1C). Immunohistochemistry of the metastasis was negative for p63 and E-cadherin (Figure 1D). Microscopy of the second tumor in the upper outer quadrant revealed a grade 2 invasive ductal carcinoma that demonstrated strong E-cadherin expression on immunohistochemistry (Figure 1E and F). No ectopic breast tissue was identified.

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Figure 1.

(A) Histological sections of the invasive lobular carcinoma (hematoxylin and eosin stain [H&E]). (B) The tumor cells are negative for E-cadherin. (C) Histological section of a positive lymph node (H&E). The sharply circumscribed oval tumor deposits show comedo-type necrosis, morphologically indistinguishable from high grade DCIS. (D) The tumor cells are negative for E-cadherin and p63, respectively, on immunostaining, confirming metastatic lobular carcinoma. (E) Invasive ductal carcinoma (H&E). (F) The tumor cells are positive for E-cadherin.

Discussion

Metastatic breast cancer resembling DCIS is a rare phenomenon that has been described in studies^1-8 in the context of metastatic ductal carcinoma. To our knowledge, metastatic lobular carcinoma exhibiting this pattern has not been reported.

Reviewing 200 cases of metastatic human breast cancer using histopathological, digital image, and immunocytochemical analyses, Barky et al ² revealed a 21% incidence of DCIS growth pattern within axillary nodal metastases. The authors concluded that the features represented cellular populations epigenetically derived from the primary tumor, capable of reverting back to their in situ growth state, and referred to the phenomenon as “revertant” DCIS. Earlier observations of this process were published by Cowen ¹ in 1980 and Lee et al ² in 1995. A summary of the published literature on DCIS-like metastasis is in Table 1.

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Table 1.

Summary of Literature on DCIS-Like Metastasis.

References	Number of Cases	Morphology of Metastasis	Immunohistochemistry
Cowen 1	1	Comedo DCIS	None
Lee et al 2	1	Micropapillary DCIS	α-SMA, vimentin, S100, collagen IV, laminin, and reticulin
Barsky et al 3	42	All types—comedo, intermediate (non-comedo), well differentiated (non-comedo) including solid, micropapillary, and cribriform	Laminin, collagen IV, SMA, S100, maspin, Her2/neu, p53, ki-67, ER, and EGFR
Cserni 4	1	Solid papillary DCIS	SMA, collagen IV, ER, chromogranin, NSE, PR, synaptophysin, and Her2/Neu
Coyne 5	2	Comedo DCIS and cribriform DCIS	SMA, calponin, p63, CD10, and CK14
Kordel 6	2	Comedo DCIS and micropapillary DCIS	SMA, S100, CK5/6, p63, CD10, and 34β12
Elghobashy and Shaaban 7	1	Comedo DCIS	SMM, p63
Pervez and Khan 8	4	Comedo DCIS	Myoepithelial and basement membrane markers
Current study	1	DCIS-like invasive lobular carcinoma	E-cadherin and p63

Abbreviation: DCIS, ductal carcinoma in situ.

While the “revertant” DCIS patterns in the lymph nodes simulated DCIS in the breast, they, however, lack a myoepithelial layer on immunohistochemical analysis. The phenomenon should be differentiated from primary DCIS arising in accessory ¹⁰ or ectopic breast tissue ¹¹ in which a myoepithelial layer should be demonstrated by immunohistochemistry. Evidence of residual normal breast tissue is another clue.

Invasive lobular carcinoma, which represents 5% to 15% of invasive breast tumors, has different clinical and pathological characteristics from ductal carcinoma. ¹² PLC is a rare form of lobular carcinoma with aggressive clinical features and worse prognostic factors. Morphologically, PLC has a growth pattern typical of lobular carcinoma, but has a higher degree of cellular atypia and a higher mitotic activity than classical lobular carcinoma. It is often associated with pleomorphic carcinoma in situ with comedo-type necrosis, ⁹ and unlike invasive ductal carcinoma, there is loss of E-cadherin on immunohistochemistry.

Our observation supports the hypothesis that metastatic lobular carcinomas can morphologically recreate their primary microenvironment at a distant site and simulate in situ growth (revertant form). However, without performing E-cadherin immunohistochemistry, the lesion could be misdiagnosed as DCIS with comedo-type necrosis or invasive ductal carcinoma.