Infiltrating ductal carcinoma breast with central necrosis closely mimicking ductal carcinoma in situ (comedo type): a case series
© Pervez and Khan; licensee BioMed Central Ltd. 2007
Received: 26 April 2007
Accepted: 08 September 2007
Published: 08 September 2007
Here we present a series of infiltrative ductal carcinoma breast cases (infiltrative ductal carcinoma with central necrosis) so closely mimicking 'DCIS with central comedo necrosis' that on initial morphological analysis these foci of tumors were labeled as DCIS (high grade, comedo). However on further histological work up and by using immunohistochemistry (IHC) for myoepithelial markers it was later confirmed that these were foci of infiltrative ductal carcinoma breast with central necrosis. This case series gives the realization that a breast carcinoma may be partly or entirely DCIS like yet invasive. In such a dilemma IHC especially for assessment of myoepithelial lining is very useful to differentiate DCIS comedo from invasive carcinoma with central necrosis.
Proliferation of malignant epithelial cells within the ducts of the breast that show no light microscopic evidence of invasion through the basement membrane into the surrounding stroma is known as ductal carcinoma in situ (DCIS). Several morphologic patterns of DCIS are recognized, the most common of which are comedo, cribriform, solid, micro papillary and papillary. DCIS-comedo is diagnosed when at least one duct in the breast is filled and expanded by large, markedly atypical cells and has abundant central luminal necrosis . It is well appreciated that infiltrating ductal carcinoma breast may mimic the diverse patterns of DCIS, the prototype of this being the infiltrating cribriform carcinoma .
Similarly here for the first time we present a series of infiltrative breast cancer cases (Infiltrative ductal carcinoma with central necrosis) so closely mimicking 'DCIS with central comedo necrosis' that on initial morphological analysis these tumors or foci were labeled as DCIS (high grade, comedo). However when axillary nodes were sampled, very similar morphologic pattern was seen in lymph node metastasis prompting immunohistochemical (IHC) studies on original biopsies with myoepithelial & basement membrane markers. This revealed a deficient/absent basement membrane & myoepithelial layer confirming the infiltrative nature of the initially diagnosed comedo type DCIS.
A 60 year old woman presented with a breast lump of 5.5 × 3 × 2.5 cm extensively sampled. On histology it was assessed as extensive comedo DCIS with occasional foci of invasion. However 35 out of 38 axillary lymph nodes showed extensive metastasis with pattern largely identical to what was reported high grade comedo DCIS. IHC for myoepithelial markers on original biopsy specimen again confirmed invasive nature of the DCIS comedo like foci with lack of myoepithelium.
A 45 year old woman's breast lump was reported as infiltrating ductal carcinoma (20%) with high grade DCIS Comedo (80%).Three out of twenty Lymph nodes showed extensive metastasis with similar DCIS Comedo like pattern. IHC again confirmed the invasive nature of the foci what was initially called as high grade DCIS. The size of the invasive component was recalculated for staging as IDC (70%); DCIS Comedo (30%).
A 42 year old woman presented with a breast lump of 2.5 × 2 × 2 cm reported as high grade comedo type DCIS. Lymph nodes were negative. Estrogen Receptor was positive, Progesterone Receptor was negative and HER2 by IHC was 3+ in what was called DCIS Oncologist denied the role of Herceptin as a part of therapy as HER2 expression was in DCIS only with no invasive component present. On review and IHC for myoepithelium, these foci lacked the myoepithelial layer and were relabeled as invasive carcinoma with central necrosis. Subsequently the patient was treated with Herceptin.
The risk factors for the development of invasive breast cancer and DCIS are similar. A further dilemma in the classification and histological analysis of DCIS is micro invasion. DCIS with micro invasion (DCISM) may also result in axillary lymph node metastases, whereas patients with DCIS should not, by definition, have axillary metastases. A higher suspicion for axillary metastases with DCISM can be obtained from the primary tumor characteristics. Statistically significant independent predictors of lymph node metastases in DCISM are comedo DCIS (P < 0.03) and the number of DCIS-involved ducts (P < 0.002) .
On pure morphological assessment a potential diagnostic trap is invasive ductal carcinoma with central necrosis. As the name indicates the tumor has a comedo DCIS like appearance and is likely to be diagnosed as DCIS comedo while in reality it is infiltrative breast carcinoma with central necrosis. This situation is identical to invasive cribiform carcinoma, a rare form of breast malignancy which very closely mimics cribriform DCIS . The most important aspect of this concept is the realization that a breast carcinoma may be partly or entirely DCIS like, yet invasive. Recently a solid variant of invasive cribriform carcinoma is also described . Similar morphologic patterns are also seen in salivary duct tumors, sweat gland carcinomas  and high grade prostatic adenocarcinomas. In case of the entire morphology having this feature, it is possible to report primary tumor as DCIS, following a conservative approach without further work up or axillary lymph node sampling. The other more common scenario is to incorrectly asses the size of the invasive component resulting in incorrect pTNM staging and management as pathological tumor size for classification (pT) is a measurement of only the invasive component .
The number of new breast cancer cases especially DCIS have increased multifold over the past decade owing to improved diagnostic testing especially mammography. This potential serious diagnostic error confusing high grade DCIS comedo with invasive carcinoma with central necrosis may be avoided by using IHC staining for myoepithelial markers and at times by subtle morphologic clues like stromal reaction.
We are grateful to technical staff who at the Aga Khan University Hospital Pakistan who helped us in preparing the histopathological slides.
A written consent was obtained from the patient(s) for the publication of the case series
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