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Secretions are seen in a range of breast cancer that includes invasive ductal carcinoma, mucinous carcinoma and secretory carcinoma. Evaluation of the quantity and location of secretions and the contours of the cell clusters complement cell morphology could improve diagnostic cytopathological criteria.
To identify the range of breast carcinomas with secretions on fine-needle aspiration.
A retrospective study of 160 patients with breast carcinoma was carried out. The tumors were typed by evaluating the quantity and location of secretions, cellularity and nuclear grade.
Secretions were seen in 16 of 160 breast carcinomas. Eleven were invasive ductal carcinoma (IDC), three were mucinous and two were secretory carcinomas. In IDC, minimal intracytoplasmic secretions were seen in 10, nuclear grades of 2 and 3 in 9, cell clusters with irregular margins in 6, and necrosis in 4. All mucinous and secretory carcinomas were nuclear grade 1. Extensive extracellular secretions and cell clusters with rounded contours were seen in mucinous carcinomas. In secretory carcinomas, the secretions were predominantly intracellular; stringy vasculature was a unique feature.
Secretions in breast cancer are seen in a range of lesions that include IDC, mucinous, and secretory carcinomas. The quantity and location of secretions in breast cancer offer clues to differentiating these.
The secretory function of the breast becomes apparent with the appearance of secretions in the epithelial cells during the third trimester of pregnancy. Expectedly, therefore, secretions are observed in some lesions of the breast, including carcinomas, which may show intracellular[1,2] or extracellular secretions.[3,4]
Mucinous and secretory carcinomas of the breast are uncommon compared to the IDC and lobular variants, but need to be recognized because of their better prognosis and low rate of lymph-node metastasis.[2,3]
The objective of this study was to a) identify the range of lesions that yielded intracellular and extracellular secretions and b) attempt to distinguish lesions with secretions by evaluating quantity and location of secretions in relation to morphology of the malignant cells on fine-needle aspiration cytology (FNAC).
In this retrospective study, cytology smears from 160 patients with diagnoses of carcinoma of the breast over a 2-year period were reviewed. Both May-Grünwald-Giemsa (MGG) and Papanicolaou stained smears were available. Secretions were assessed on MGG stained smears and nuclear grade was assessed on Papanicolaou. Cases with intracellular and/or extracellular secretion were subclassified into IDC, mucinous carcinoma, and secretory carcinoma by the existing criteria.[1–3] Cellularity, location and extent of secretion, and nuclear grade (nuclear size, nucleoli, chromatin pattern and nuclear membrane)were documented. The amount of intracellular and/or extracellular secretion was quantified as minimal (less than 10%), moderate (up to 50%), or extensive (more than 50%) of the material present on each slide. Presence and absence of necrosis was also noted.
All 160 patients were females, with age ranging from 25 to 61 years (median 49 years). The lumps varied from 1 to 4 cm in size. Multiple aspirates had been performed in tumors larger than 2 cm. All tumors were unilateral and solitary. Secretions were seen in 16 tumors of three tumor types: IDC (11), mucinous carcinoma (3), and secretory carcinoma (2).
IDC yielded cellular aspirates (10/11). Predominantly dispersed cells of nuclear grade 2 and 3 were also present in this group. Secretions were minimal and intracellular in the majority (10/11) [Figure 1]. Two patients had extracellular secretions: In one patient, these were minimal and associated with intracellular secretions and in the other, only extracellular secretions in moderate quantity were present [Table 1]. Both these cases were identified as IDC because of their nuclear grade and presence of cell clusters that had irregular margins [Figure 2]. Necrosis was present only in IDC.
Mucinous carcinomas had abundant, mucoid aspirates. Extensive extracellular secretion predominated. Small cell clusters with rounded contours [Figure 3], single cells, signet cells, and thin-walled “chicken-wire” vascular channels were seen floating in the secretions. Nuclear grade was 1.
Secretory carcinoma had abundant, cellular aspirates of nuclear grade 1. Cells were predominantly in loosely cohesive clusters and some papillary fragments. Small clusters and single polygonal cells appeared strung on capillaries [Figure 4]. Cytoplasm was abundant, foamy or granular, with extensive secretory vacuoles. Signet cells and minimal extracellular mucoid material associated with grape-like mucous globular structures were also present.
Mucinous and secretory carcinomas of the breast are uncommon and indolent tumors.[7–10] A conservative surgical approach for treatment is advocated because of their better prognosis. Morphological identification on FNAC is an important step in the workup.
In this study, we quantified the secretions in aspirates from breast carcinomas on a 3-point scale as minimal, moderate and extensive. Both mucinous and secretory carcinomas had extensive secretions. As noted by others, while these were extracellular in mucinous carcinomas,[1,2,9,10] secretory carcinomas were characterized by predominantly intracellular secretions.[3,4] Thus, quantifying the secretions and characterizing their location appears to be useful in separating these two lesions.
Extracellular secretions have been described in mucinous carcinoma and some IDC. Mucinous carcinoma is characterized by poorly cellular, abundant mucoid aspirate, extensive extracellular secretion, thin-walled vessels and few single and small clusters of cells floating in the secretions.[1,2,11–14] We observed that the cell clusters comprised uniform cells with rounded contours reminiscent of those seen in tissue sections. Conversely, IDC with extracellular secretions, often mistaken for mucinous carcinoma, showed at least some cell clusters with irregular margins as in conventional IDC. Besides, the secretions in IDC were minimal to moderate compared to extensive in mucinous carcinoma. High nuclear grade in IDC with extracellular mucin has been used to differentiate mixed IDC and mucinous carcinoma. We propose that a careful search for the characteristic irregular margins of cell clusters is necessary and should be used as an additional distinguishing feature of IDC.
Mucocoele-like tumors need to be distinguished from mucinous carcinoma; however, being benign lesions, these are outside the scope of this study. In the literature, they are described as being characterized by an abundance of mucin and poor cellularity; the cells are present as monolayered sheets of epithelial cells.[1,10]
Intracellular secretions have been described in secretory carcinoma,[3,15–17] lobular carcinoma[5,18] and some IDC. Though the morphological features on histopathology suggest that the secretions in secretory carcinoma are extensive in both extracellular and intracellular locations,[7,16] in cytopathology smears there are predominantly intracellular secretions with minimal mucoid material in proximity to epithelial cells, and mucous globular structures.[3,16,17] As visualized by transmission electron microscopy, the secretions are intracellular, within intracytoplasmic lumens, or present in extracellular lumens which are several times larger than the intracellular lumens. The latter are probably the mucous globular structures seen in cytology smears. In both our patients with secretory carcinoma, we observed small cellular clusters and single cells appearing to be strung on capillaries, probably caused by disintegration of papillary structures while smearing.
Intracytoplasmic lumens have also been described in lobular carcinoma and IDC. We did not encounter a single case of lobular carcinoma. Poor cellular yield, small hyperchromatic nuclei and nuclear molding have been described to characterize lobular carcinoma. In contrast, IDC are cellular, with high nuclear grade (nuclear enlargement and pleomorphism), and distinct cytoplasm.[5,18,20]
None of our cases of mucinous and secretory carcinomas had necrosis. However, necrosis was encountered in four cases of high-grade ductal carcinomas with secretions. These observations are not unexpected as mucinous and secretory carcinomas are low-grade tumors.
To conclude, secretions are seen in a range of breast cancer that includes invasive ductal carcinoma, mucinous carcinoma and secretory carcinoma. Evaluation of the quantity and location of secretions and the contours of the cell clusters complement cell morphology, and could improve diagnostic cytopathological criteria. Small cellular clusters and single cells appearing to be strung on capillaries should be considered additional distinguishing features of secretory carcinoma.
Source of Support: Nil
Conflict of Interest: None declared.