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CASE REPORT Table of Contents   
Year : 2010  |  Volume : 53  |  Issue : 3  |  Page : 537-540
Solid variant of papillary carcinoma of nipple: An under recognized entity

Department of Pathology, Sri Ramachandra University, Porur, Chennai - 600 116, India

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Date of Web Publication22-Oct-2010


Papillary lesions of the breast represent a heterogeneous group with differing biological behavior. Solid papillary carcinomas are uncommon tumors composed of circumscribed large cellular nodules separated by bands of fibrosis. Correct diagnosis is crucial but may be difficult, as many other benign and malignant lesions have similar histological appearances. Immunohistochemistry plays a useful role in their differentiation. We describe one such case of a solid variant of papillary carcinoma of the left nipple in a 75-year-old woman, who had no other palpable mass in rest of the breast tissue. The case is documented for the rarity of its occurrence and significance of recognition of this lesion.

Keywords: Breast, nipple, papillary carcinoma, solid variant

How to cite this article:
Sundaram S, Prathiba D, Rao S, Rajkumar A, Rajendiran S. Solid variant of papillary carcinoma of nipple: An under recognized entity. Indian J Pathol Microbiol 2010;53:537-40

How to cite this URL:
Sundaram S, Prathiba D, Rao S, Rajkumar A, Rajendiran S. Solid variant of papillary carcinoma of nipple: An under recognized entity. Indian J Pathol Microbiol [serial online] 2010 [cited 2021 Sep 23];53:537-40. Available from: https://www.ijpmonline.org/text.asp?2010/53/3/537/68293

   Introduction Top

The solid variant of papillary carcinoma of the breast is an uncommon entity, which generally presents in the seventh or eighth decade and may be associated with underlying invasive carcinoma. Myoepithelial markers can help in differentiating papilloma from papillary carcinoma, as the former usually shows a continuous layer of myoepithelial cells. We describe a case of solid variant of papillary carcinoma of nipple, which probably originated from the duct within the nipple or the lactiferous sinus beneath the nipple.

   Case Report Top

A 75-year-old woman presented with a firm nodular swelling in the left nipple with no other palpable mass elsewhere in the breast. Mammography showed a hyperdense lesion just beneath the left nipple [Figure 1]. There were no palpable lymph nodes in the axilla. A wide excision of the lesion was performed along with nipple and areola and sent for histopathological examination.
Figure 1: Mammogram showing an irregular hyperdense lesion in the nipple region

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Pathological Examination

The specimen received for histopathology showed a partially skin-covered tissue with nipple and areola measuring 4 Χ 3 x 1 cm. The cut surface showed a well-circumscribed, solid firm grey-white area measuring 3 Χ 2 cm situated just beneath the skin with relatively smooth border. Histopathological examination showed a tumor in the subepithelial region composed of solid nodules of neoplastic cells with the presence of a rich delicate network of fibrovascular stroma distributed in an arborizing pattern throughout the tumor. Formation of fibrovascular cores was evident in some areas with cells arranged in lobules in a cribriform pattern separated by the fibrous stands [Figure 2]. The cells were uniformly round to polygonal with a moderate amount of cytoplasm. Mitosis was scant. Although the tumor nodules were relatively circumscribed, there were foci showing infiltration of the adjacent tissue.
Figure 2: Nipple with sub-epithelial region showing tumor cells arranged in lobules (H and E, ×200); inset shows uniform round-to-oval tumor cells with moderate amount of cytoplasm (H and E, ×400)

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A differential diagnosis of skin adnexal tumor, ductal and lobular carcinoma in situ and invasive ductal carcinoma was considered. Immunohistochemistry for ER (estrogen receptor), PR (progesterone receptor), epithelial membrane antigen (EMA), E-cadherin, S100, Her-2-neu were performed. ER [Figure 3], PR, EMA and E-cadherin [Figure 4] were all positive. Her-2-neu was negative. S-100 was negative in the tumor cells but positive in the myoepithelial cells of adjacent normal ducts [Figure 5]. Chromogranin stain was also done and to our surprise found to be positive [Figure 6]. In view of these findings, a diagnosis of solid variant of papillary carcinoma of the nipple was considered.
Figure 3: Nuclear positivity seen in tumor cells (Immunostain estrogen receptor, ×100)

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Figure 4: Tumor showing strong cytoplasmic staining in the tumor cells (Immunostain E-cadherin, ×100)

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Figure 5: Immunostain for S100 negative in the tumor cells with the myoepithelial cells in the adjacent normal ducts showing nuclear and cytoplasmic positivity (Immunostain S100, ×400)

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Figure 6: Immunostain for chromogranin showing cytoplasmic positivity in the tumor cells (Immunostain chromogranin, ×400)

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   Discussion Top

The nipple and areola are often evaluated as a separate region because of the intricacy of its anatomical structures. Common benign neoplastic lesions of nipple include duct adenoma and syringomatous adenoma. Malignant lesions of the nipple are more commonly due to extension from primary tumor in the breast. Some of them may manifest as Paget's disease of the nipple. [1] Solid variant of papillary carcinoma of the breast is a rare and distinct entity that typically occurs in the nipple region of elderly women. It is also termed as a well-differentiated neuroendocrine carcinoma of the breast or mucinous carcinoid (in older times), as it shows chromogranin positivity. They usually have a cribriform pattern. It is also associated with mucin and low mitosis. The clue to the diagnosis is presence of cores of vessels within the nests of tumor. In the present case, the cells were arranged in lobules and in a cribriform pattern separated by fibrous stands. The cells were uniform round to polygonal in shape with moderate amount of cytoplasm. Mitoses were scant.

The differential diagnosis considered were skin adnexal tumor, ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS) and invasive ductal carcinoma.

Although it is not very difficult to distinguish DCIS and LCIS, they may possess overlapping microscopic features creating diagnostic confusion. Ductal carcinoma in situ may extend into the recognizable lobules while LCIS may involve extra-lobular ducts thus mimicking DCIS. Cells of DCIS are more cohesive and have characteristic architectural pattern. In contrast, LCIS cells are smaller ductal carcinoma in situ, more uniform and discohesive. There has been no general agreement regarding in situ lesions with indeterminate features. In such situations, E-cadherin immunostaining may be of help since the expression is lost in invasive lobular carcinoma and in LCIS. In our case, E-cadherin was negative, thus favoring a ductal carcinoma. The possibility of skin adnexal tumor was also considered because of the location and presence of bland round-to-oval cells in a well-circumscribed tumor. However, most adnexal tumors are positive for S-100 and negative for ER and PR. In the present case, both ER and PR were found to be strongly positive and S100 was negative in the tumor cells, thus ruling out the possibility of skin adnexal tumor.

In the present case, a solid tumor was seen located beneath the left nipple. It predominantly showed a cribriform pattern with monomorphic cells. Nuclei of the cells were round, vesicular, without obvious pleomorphism. Focal areas, however, showed invasion into the adjacent fat. Immunostain for S100, which highlights the myoepithelial cells, was negative in the tumor islands but positive in the adjacent ducts indicating invasive nature of the cells. The ER and PR positivity of the cells confirmed that the lesion was of mammary origin. E-cadherin positivity confirmed the tumor to be of the ductal origin and absence of the myoepithelial cells described the invasiveness of the lesion. There was no other lesion in the rest of the breast tissue suggesting that the lesion was arising primarily from the ducts in the nipple region. Immunostaining for chromogranin showed positive staining in the cytoplasm of the tumor cells. Hence, the diagnosis of a solid variant of papillary carcinoma of the nipple was established.

Solid papillary carcinoma (SPC) of the breast is an unusual variant of papillary carcinoma with a solid pattern of expansile growth. They are composed of circumscribed large cellular nodules separated by bands of dense fibrosis. In an analysis of 58 cases of SPC, it was found that the mean age was 72 years and their behavior was indolent. Lymph node and distant metastases are uncommon and generally limited to cases with (conventional) invasive components. [2]

Myoepithelial markers can help in differentiating papilloma from papillary carcinoma, as the former usually shows a continuous layer of myoepithelial cells. In intracystic papillary carcinoma, there is controversy as to the presence of a complete myoepithelial cell layer around these lesions. p63 is the marker of choice as the staining is nuclear, cross-reactivity is minimal and sensitivity is high. Papilloma may frequently be complicated by superimposed different types of epithelial hyperplasia, which range from usual to atypical or even DCIS, and they may be morphologically similar. Basal cytokeratins (CKs) are useful to differentiate these entities, as chronic hyperplasia is positive for basal CKs with a mosaic staining pattern. CK5/6 is probably the best marker. Neuroendocrine markers (chromogranin A and synaptophysin) may be positive in papillary carcinoma, particularly in the solid type. Therefore, a panel of CK5/6, p63 and neuroendocrine markers can be useful in the diagnostic investigation of problematic papillary lesions of the breast. [3]

In a study of 11 cases by Nicholas et al., [4] it was found that 73% lacked myoepithelial cell markers in some foci. Solid papillary carcinoma of the breast frequently lacks myoepithelial markers at the tumor-stromal interface in spite of a circumscribed non-invasive appearance. Metastases from such tumors are infrequent, but can occur in cases that lack myoepithelial marker expression by immunohistochemistry. [4] Our case also showed loss of myoepithelial cells. Solid papillary ductal carcinoma in situ (SP-DCIS) shares many morphological features with usual ductal hyperplasia (UDH). Another study report showed that the absence of strong cytokeratin 5/6 expression by SP-DCIS distinguishes it from its morphological mimic, UDH. [5]

In a study of 21 cases, SPC was found to mainly affect elderly females and had distinctive pathologic and immunophenotypic features. Some cases of SPC were associated with mucinous and neuroendocrine components. Follow-up data of the study suggested that SPC often carried an indolent clinical behavior and favorable prognosis. [6]

Early diagnosis of the lesion, localized only to the nipple, would require wide excision of the tumor. However, mastectomy would be the treatment of choice, if the lesion spreads into the rest of the breast tissue. The patient in the present case had been followed-up for 12 months and is now disease-free.

   Conclusion Top

Solid variant of papillary carcinoma of the nipple is a rare and under-recognized lesion, and its identification is important as it may be overlooked during clinical examination. Immunostain particularly chromogranin plays a pivotal role in distinguishing it from other morphologically similar lesions.

   References Top

1.Anderson JA, Gram JB, Patterson RM. Involvement of nipple and areola in breast cancer. Value of clinical findings. Scand J Plast Reconstr Surg 1981;15:39-42.  Back to cited text no. 1      
2.Nassar H, Qureshi H, Volkanadsay N, Visscher D. Clinicopathologic analysis of solid papillary carcinoma of the breast and associated invasive carcinomas. Am J Surg Pathol 2006;30:501-7.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]  
3.Tse GM, Tan PH, Moriya T. The role of immunohistochemistry in the differential diagnosis of papillary lesions of the breast. J Clin Pathol 2009;62:407-13.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]  
4.Nicolas MM, Wu Y, Middleton LP, Gilcrease MZ. Loss of myoepithelium is variable in solid papillary carcinoma of the breast. Histopathology 2007;51:657-65.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]  
5.Rabban JT, Koerner FC, Lerwill MF. Solid papillary ductal carcinoma in situ versus usual ductal hyperplasia in the breast: A potentially difficult distinction resolved by cytokeratin 5/6. Hum Pathol 2006;37:787-93.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]  
6.Wei B, Bu H, Chen HJ, Zhang HY, Li XJ. Clinicopathologic study of solid papillary carcinoma of breast. Zhonghua Bing Li Xue Za Zhi 2006;35:589-93.  Back to cited text no. 6  [PUBMED]    

Correspondence Address:
Sandhya Sundaram
877, Vaigai Colony, 15th Street Block, Annanagar, Chennai - 600 040
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.68293

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

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