Diagnosis -- Metastatic Neuroendocrine Tumor (carcinoid) of GI Origin

FINAL DIAGNOSIS

Metastatic neuroendocrine tumor (carcinoid) of GI origin (favor pancreas, upper GI/small bowel over colorectal)

DISCUSSION

This case highlights the need to keep metastatic neuroendocrine tumors (NET) in the differential diagnosis of breast lesions, particularly those that appear to be low-grade/well differentiated and yet do not express strong ER/PR. The index case had a history of ileocecal neuroendocrine tumor which was not available at the time of diagnosis.

Metastases to the breast are uncommon, accounting for less than 1% of all malignant breast neoplasms (1). Most of the metastases arise from the ovary, lung, contralateral breast or hematopoietic malignancies (1, 2, 4). Other primary sites include stomach, kidney, and skin. Metastatic gastrointestinal neuroendocrine neoplasms to the breast are very infrequent entities and comprise only 0.5% to 1% of all metastatic tumors to the breast with only a few isolated case reports described in literature (3, 4 and 5). Hence NET metastasizing to the breast is diagnostically challenging.

In addition, NETs may show morphologic features resembling in-situ and invasive primary breast carcinomas, including ductal, lobular and specialized types of tumor (especially solid papillary carcinoma), with and without neuroendocrine differentiation (3, 4 and 5). Correct diagnosis requires correlation with histologic features, immunohistochemistry findings, and clinical features. If a low/intermediate grade neoplasm in the breast exhibits neuroendocrine cytoarchitectural features, with diffuse, strong staining for neuroendocrine marker(s), absence of associated in-situ carcinoma, and negativity for ER and GATA3, the possibility of a metastatic neuroendocrine neoplasm should be strongly considered (6). Accurate diagnosis is essential for appropriate clinical management (5).

The diagnosis is particularly difficult in patients who present with breast masses in the absence of a known history of NET, as was in the index case. Rarely, the breast is the first presenting site of metastatic NET. In these circumstances, lack of hormone receptor positivity in lesions that otherwise appear to be low grade NET should raise the possibility of metastatic NET and prompt additional immunohistochemical workup and correlation with radiography and clinical history.

In addition, benign and malignant neoplasms that arise from cutaneous sites may be also pose diagnostic difficulties because morphologic spectrum of some adnexal tumors is similar to that of breast carcinomas. Presence of an in-situ component can be helpful in determining the primary origin. For most part the IHC may give similar results, breast specific markers may not be reliable to distinguish between the two groups of lesions (7). Hence, diagnosis may require clinical correlation as well as location and histomorphology of the lesion.

REFERENCES

  1. O'Donnell ME, McCavert M, Carson J et al (2009) Non-epithelial malignancies and metastatic tumours of the breast. Ulster Med J 78:105-112
  2. Crona J, Granberg D, Norlén O, Wärnberg F, Stålberg P, Hellman P, Björklund P. Metastases from neuroendocrine tumors to the breast are more common than previously thought. A diagnostic pitfall? World J Surg. 2013 Jul;37(7):1701-6. doi: 10.1007/s00268-013-2037-2. PMID: 23592057
  3. Perry KD, Reynolds C, Rosen DG, Edgerton ME, T Albarracin C, Gilcrease MZ, Sahin AA, Abraham SC, Wu Y. Metastatic neuroendocrine tumour in the breast: a potential mimic of in-situ and invasive mammary carcinoma. Histopathology. 2011 Oct;59(4):619-30. doi: 10.1111/j.1365-2559.2011.03940.x. PMID: 22014043.
  4. Papalampros A, Mpaili E, Moris D, Sarlanis H, Tsoli M, Felekouras E, Trafalis DT, Kontos M. A case report on metastatic ileal neuroendocrine neoplasm to the breast masquerading as primary breast cancer: A diagnostic challenge and management dilemma. Medicine (Baltimore). 2019 Apr;98(16):e14989. doi: 10.1097/MD.0000000000014989. PMID: 31008928; PMCID: PMC6494217.
  5. Clark, Beth Z. MD; Bhargava, Rohit MD Metastatic Neuroendocrine Tumors to the Breast, AJSP: Reviews & Reports: September/October 2017 - Volume 22 - Issue 5 - p 269-274.
  6. Mohanty SK, Kim SA, DeLair DF, Bose S, Laury AR, Chopra S, Mertens RB, Dhall D. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation. Mod Pathol. 2016 Aug;29(8):788-98. doi: 10.1038/modpathol.2016.69. Epub 2016 Apr 29. PMID: 27125358.
  7. Rosen, P. P. (1997). Rosen's breast pathology. Philadelphia: Lippincott-Raven.


Contributed by Vandana Baloda, MD, Sonal Choudhary, MD and Rohit Bhargava, MD



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