LETTER TO EDITOR
Year : 2009 | Volume
: 52 | Issue : 4 | Page : 583--585
Chemotherapy induced cytomorphologic changes in breast carcinoma: A potential diagnostic challenge for the histopathologist
Ruchika Gupta, Raman Arora, Alok Sharma, Amit Kumar Dinda
Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110 029, India
162, Pocket-B, Sarita Vihar, New Delhi-110 076
|How to cite this article:|
Gupta R, Arora R, Sharma A, Dinda AK. Chemotherapy induced cytomorphologic changes in breast carcinoma: A potential diagnostic challenge for the histopathologist.Indian J Pathol Microbiol 2009;52:583-585
|How to cite this URL:|
Gupta R, Arora R, Sharma A, Dinda AK. Chemotherapy induced cytomorphologic changes in breast carcinoma: A potential diagnostic challenge for the histopathologist. Indian J Pathol Microbiol [serial online] 2009 [cited 2021 Sep 27 ];52:583-585
Available from: https://www.ijpmonline.org/text.asp?2009/52/4/583/56128
Neoadjuvant chemotherapy, administered pre-operatively, is now the standard-of-care therapy for locally advanced breast cancer. , In cases where the tumor shows partial or no response to chemotherapy, the tumor cells may appear unaltered or exhibit certain morphologic changes, which interfere with nuclear grading of the tumor. 
We describe the case of a 40-year-old female who presented with a right breast mass detected one month prior to the presentation. There was no history of nipple discharge or family history of breast carcinoma. Local examination showed a 10Χ8 cm firm to hard mass in the upper inner quadrant of right breast. There was no fixity to the overlying skin or the chest wall. Axillary lymph nodes were not palpable clinically. Mammography showed a speculated mass in the upper inner quadrant of right breast, suggestive of malignancy (BIRADS 5). A biopsy from the breast mass showed features of an invasive ductal carcinoma (not otherwise specified, NOS type) with minimal tubule formation, moderate nuclear pleomorphism [Figure 1]a and frequent mitotic figures (Scarff-Bloom-Richardson grading 3+2+2=7). Immunohistochemistry showed the tumor cells to be negative for estrogen and progesterone receptor [Figure 1]b,c. Her2/neu staining showed strong membranous positivity in >30% of tumor cells (score 3+) [Figure 1]d. The patient received four cycles of neoadjuvant chemotherapy (Docetaxel and Epirubicin). After completion of the chemotherapy regime, there was significant reduction in the size of primary tumor. A skin-sparing right mastectomy with right axillary dissection was performed.
The specimen measured 22.5Χ14Χ6.5 cms. Careful serial slicing failed to reveal any gross residual tumor. Multiple histologic sections were taken from the upper inner quadrant (site of primary tumor) to detect any residual tumor and to assess the chemotherapy-induced changes. These sections revealed two microscopic foci of invasive ductal carcinoma [Figure 2]a, morphologically almost similar to the tumor seen in the core biopsy. In vicinity of the tumor islands, scattered singly-lying large cells were seen with a size approximately four times of the tumor cells present in islands. These large cells showed vacuolization of cytoplasm, large hyperchromatic bizarre nuclei with coarse chromatin clumping [Figure 2]b,c. Few multinucleated cells were also noted. Immunohistochemically, these large cells stained positively for pancytokeratin [Figure 2]d, confirming that these were altered tumor cells. Adjacent breast showed dense fibrosis, chronic inflammatory infiltrate, and hemosiderin-laden macrophages. Axillary lymph nodes were free of tumor. Thus, the final diagnosis rendered was microscopic foci of residual tumor with cytologic changes of neoadjuvant chemotherapy.
Neoadjuvant chemotherapy is being widely used in the pre-operative management of locally advanced breast cancers. The histologic effects of chemotherapy include a decrease in the tumor cellularity, which may be extreme so that no residual tumor cells are detected. Such a response has been reported in up to 10% of patients.  Healed foci of infiltrating carcinoma show architectural distortion in the form of fibrosis, stromal edema, increased vascularity and chronic inflammatory cell infiltrate.  The residual tumor cells, whether intraductal or invasive, may appear morphologically unaltered or show cytologic changes reflecting effects of therapy. The tumor cells are large due to increased cytoplasm which may contain vacuoles or eosinophilic granules.  There is associated nuclear enlargement, pleomorphism, and hyperchromasia. However, multinucleation and atypical mitotic figures are not conspicuous.  The recognition of these changes assumes greater importance in cases where altered tumor cells are present individually. In these cases, the tumor cells may be mistaken for histiocytes showing reactive changes and in such instances, immunoreactivity for cytokeratin and epithelial membrane antigen is helpful in diagnosis of residual tumor cells. Histologic grading of tumor cells is an important prognostic factor in breast carcinoma. A study comparing histologic grading in pre-therapy and post-therapy specimens did not reveal significant differences in grading.  Other studies, however, reported increase in nuclear grade in one-third of cases.  Cytologic changes like lobular atrophy and cytologic atypia in duct and lobular epithelial cells may be seen in non-neoplastic breast parenchyma. Such changes may be worrisome, however comparison with a pre-treatment specimen is helpful.  The clinical and histologic assessment of axillary lymph nodes after neoadjuvant chemotherapy may be difficult due to smaller metastases in fewer lymph nodes and apparent clinical down-staging.  Fibrosis and hyalinization are also frequent in lymph nodes; metastatic deposits may be seen in or around these hyalinized areas. 
On conclusion, a meticulous gross examination of post-chemotherapy breast excision specimens is required with ample sectioning to identify the small foci of residual tumor. The pathologist should be aware of the possible nuclear and cytoplasmic changes of chemotherapy. Special stains may be required to confirm the nature of atypical scattered individual cells. Grading of post-chemotherapy breast carcinoma may not be a prognostic indicator, due to the cytomorphologic changes in the tumor cells.
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