| Abstract|| |
Metastases to breast are much rarer than primary breast tumors. We now present a case of 45-year-old female, who presented with an isolated breast mass. A positron emission tomography-computed tomography (PET-CT) done revealed hypermetabolic right breast nodules, soft tissue deposits, and multiple nodal involvement. The biopsy from the breast and axillary lymph node showed dense lymphoid infiltrate and was interpreted initially as granulomatous inflammation. However, the lumps were hard and suspicious for primary breast cancer, so an immunohistochemistry for cytokeratin was performed which highlighted the epithelial cell clusters masked within the inflammatory infiltrate and the diagnosis of undifferentiated carcinoma, lymphoepithelioma-like was made. After the diagnosis was made, it was realized that the patient had been treated earlier for a nasopharyngeal carcinoma (NPC). The in situ hybridization (ISH) test for Epstein–Barr virus-encoded RNA ISH was positive in the tumor cells, and hence, a diagnosis of metastatic NPC was finally made. The patient subsequently developed extensive nodal, skeletal, and soft tissue metastatic disease but was alive till September 2015. Although extremely rare, metastatic NPC can occur in the breast and the above case highlights that it mimics an inflammatory lesion. This case highlights the importance of the multidisciplinary approach for appropriate tumor diagnosis and patient management.
Keywords: Epstein–Barr virus-encoded RNA-in situ hybridization, metastases to breast, nasopharyngeal carcinoma
|How to cite this article:|
Pai T, Nair N, Pantvaidya G, Deodhar K, Shet T. Metastatic nasopharyngeal carcinoma presenting as an isolated breast mass: A diagnostic pitfall and a review of literature. Indian J Pathol Microbiol 2017;60:119-21
|How to cite this URL:|
Pai T, Nair N, Pantvaidya G, Deodhar K, Shet T. Metastatic nasopharyngeal carcinoma presenting as an isolated breast mass: A diagnostic pitfall and a review of literature. Indian J Pathol Microbiol [serial online] 2017 [cited 2017 Mar 24];60:119-21. Available from: http://www.ijpmonline.org/text.asp?2017/60/1/119/200058
| Introduction|| |
A hard lump in the breast usually indicates a primary breast cancer. Metastases to the breast are rare accounting for approximately 2% of all mammary malignancies, most common sites being the ovaries, lung, stomach, colon, and skin. Metastatic nasopharyngeal carcinoma (NPC) is a multifocal disease involving the bones, liver, lungs, and distant lymph nodes and their metastatic nature is quite evident.
Breast is an extremely unusual site of metastatic NPC and presentation as a breast mass without evidence of tumor at primary site is uncommon. To the best of our knowledge, only eight cases of metastatic NPC to breast have been reported in literature. We now present a case of a 45-year-old female who developed breast metastasis from NPC and had the usual inflammatory infiltrate around the lesions mimicked a granulomatous inflammation histologically in addition posing a diagnostic challenge, and accurate diagnosis was obtained only after clinical discussion.
| Case Report|| |
A 45-year-old female presented to the breast unit of our institute with the complaints of right arm edema, breast mass, and axillary nodes in June 2012. On examination, right axillary lymph nodes were matted measuring 4 cm × 4 cm. There was a multinodular mass involving upper outer quadrant of the right breast. The overlying skin was edematous giving peau d'orange-like appearance. She was referred for positron emission tomography-computed tomography (PET-CT) to rule out metastatic breast cancer. PET-CT revealed hypermetabolic multiple right breast nodules, largest measuring 2.1 cm in size with standardized uptake value (SUV) max 5.2. In addition, hypermetabolic lesions were noted in right arm and scapular subcutaneous region (SUV max 3.7) and multiple lymph nodes including bilateral supraclavicular, axillary, retroperitoneal, common iliac, and bilateral external and internal iliac nodes.
Histopathological evaluation of breast biopsy revealed lobular inflammation with dense lymphoid infiltrate and ill-defined granulomatous reaction with occasional histiocytic cells [Figure 1]a and [Figure 1]b. Similarly, the axillary nodal biopsy was reported as granulomatous lymphadenitis. The clinical information of the patient was not available before the biopsy reporting. However, in light of the PET-CT findings, lack of clinical signs of inflammation, and hard feel of the breast nodules, case was reviewed and it was realized that the whole lesion was, however, localized and sharply defined which is unlike any inflammatory process. Furthermore, there were large nuclei with vesicular chromatin within the infiltrate that were highly atypical for an inflammatory process [Figure 1]c and [Figure 1]d. Hence, a cytokeratin immunostain (monoclonal, MNF 116, 1:300, Dako, Carpinteria, California, USA) was performed which brilliantly highlighted the epithelial cell syncytial clusters which were initially masked by the dense inflammatory infiltrate [Figure 2]. These clusters were located within normal lobules. The diagnosis of lymphoepithelioma-like undifferentiated carcinoma of breast was given. Similar histology was seen in right arm nodule and axillary node biopsy.
|Figure 1: Representative microphotographs of the breast lesion; (a and b), inflammatory infiltrate centered around lobules mimicking lobulocentric mastitis; (c and d), atypical nuclei within the infiltrate, black arrow highlighting cells with conspicuous nuclei and bizare nuclei highlighted by the red arrow (H and E, a: ×40; b: ×100, c and d: ×400)|
Click here to view
|Figure 2: Epithelial clusters within the infiltrate highlighted by cytokeratin stain (immunohistochemistry: ×100)|
Click here to view
During the joint clinic discussion, her medical history was discovered. She was diagnosed with NPC in December 2007 at an outside center, following which she was treated with external beam radiation therapy (EBRT) and 6 cycles of cisplatin-based chemotherapy till February 2008. She later developed left neck nodal recurrence in 2010 and was treated with EBRT to neck. Again, she developed neck nodal recurrence in early 2011, for which she was treated with chemotherapy and EBRT.
In the light of these findings, an in situ hybridization for Epstein–Barr virus-encoded RNA (EBER-ISH) (RISH EBER probe, Biocare, USA) was performed which highlighted the tumor cell nuclei brown [Figure 3]. All three histology samples were thus reported as metastatic undifferentiated carcinoma, nasopharyngeal type. The patient was subsequently given gemcitabine and nanoxel-based chemotherapy and was alive despite the disseminated disease till September 2015.
|Figure 3: Epstein–Barr virus-encoded RNA-in situ hybridization staining of tumor nuclei (ISH, ×400)|
Click here to view
| Discussion|| |
NPC is curable despite its tendency for regional lymph node spread. However, distant metastasis is a leading cause of mortality  and in a large series of 256 NPC cases, the incidence of distant metastasis was reported to be 36% overall (and in 51% of the 63 autopsy cases) and bones, distant lymph nodes, liver, and lungs were the most common sites involved. Breast metastases from NPC are an extreme rarity and occur usually as a part of disseminated disease. However, to begin with, the lesion may be seen involving one organ as in the case we discuss and throw the clinician and pathologist off guard.
Sham et al. for the 1st time reported two cases of NPC that metastasized to breast in 1991. Since then only a handful of reports have been added to literature [Table 1].,,,,, Majority cases including the present case had unilateral breast lesions while 2 cases had bilateral breast metastasis., Following the primary NPC, the time duration for the development of secondaries in breast is highly variable and ranged from 2 to 52 months. In our case, breast metastasis developed after 52 months following the initial treatment for NPC and 10 months after therapy for recurrence. Although rest of the cases had regional nodal and visceral metastasis, the present case is unique as it has an extensive disease involving intraabdominal lymph nodes as well as soft tissue deposits which are rare in NPC.
|Table 1: Cases of metastatic nasopharyngeal carcinoma to breast reported in literature|
Click here to view
Metastases to the breast are rare and account for approximately 2% of all mammary malignancies and are associated with poor prognosis. An accurate differentiation of metastatic from primary breast lesion is of crucial importance because of the significant impact on the patient management and to obviate surgical interventions. Radiologically, metastatic breast tumors should be suspected when a multinodular neoplasm is found in superficial tissue of the breast. In addition, the characteristic architectural distortion, microcalcification, and speculation associated with primary breast malignancy are uncommon in metastatic tumors.
The histologic differentials of NPC metastasis are mastitis and breast carcinomas accompanied by inflammatory infiltrate. The case we discuss stresses on the careful search for atypical nuclei in a lobulocentric seemingly inflammatory process in a patient with advanced NPC and a breast mass. A primary lymphoepithelioma-like carcinoma of the breast is also a differential which also displays poorly differentiated nuclear grade and dense lymphoid infiltrate. Most breast metastases, however, show multiple tumor nodules unlike primary breast cancers with similar lymphoid infiltrate which tend to be localized and produce well-defined large mass. Furthermore, the tumor cells in our case were within normal lobules a feature that indicates metastases over a primary breast cancer. EBV testing can help resolve this diagnostic dilemma as it negative in primary lymphoepithelioma of breast  and positivity favors the metastatic NPC as in the case we report.
| Conclusion|| |
This case highlights histologic features of NPC metastasis to breast and the importance of EBER-ISH and reiterates the importance of multidisciplinary approach for appropriate tumor diagnosis and patient management.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Hajdu SI, Urban JA. Cancers metastatic to the breast. Cancer 1972;29:1691-6.
Ahmad A, Stefani S. Distant metastases of nasopharyngeal carcinoma: A study of 256 male patients. J Surg Oncol 1986;33:194-7.
Liang N, Xie J, Liu F, Xu D, Yu X, Tian Y, et al.
Male breast metastases from nasopharyngeal carcinoma: A case report and literature review. Oncol Lett 2014;7:1586-8.
Li S, Yang J. Nasopharyngeal carcinoma metastasis to the mammary gland: A case report. Oncol Lett 2015;9:275-7.
Driss M, Abid L, Mrad K, Dhouib R, Charfi L, Bouzaein A, et al.
Breast metastases from undifferentiated nasopharyngeal carcinoma. Pathologica 2007;99:428-30.
Sham JS, Choy D. Breast metastasis from nasopharyngeal carcinoma. Eur J Surg Oncol 1991;17:91-3.
Yeh CN, Lin CH, Chen MF. Clinical and ultrasonographic characteristics of breast metastases from extramammary malignancies. Am Surg 2004;70:287-90.
Vaishnav KU, Pandhi S, Shah TS, Chaudhry A. Nasopharynx carcinoma: A rare primary for bilateral breast metastasis. BMJ Case Rep 2012;2012. pii: Bcr0320126083.
Leach BI, Sun B, Petrovic L, Liu SV. Breast metastasis from nasopharyngeal carcinoma: A case report and review of the literature. Oncol Lett 2013;5:1859-61.
Dadmanesh F, Peterse JL, Sapino A, Fonelli A, Eusebi V. Lymphoepithelioma-like carcinoma of the breast: Lack of evidence of Epstein-Barr virus infection. Histopathology 2001;38:54-61.
Department of Pathology, Tata Memorial Hospital, Parel, Mumbai - 400 012, Maharashtra
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3]