Multiple myeloma is a clonal proliferation in the bone marrow of neoplastic plasma cells . To make diagnosis of MM, two of the following criteria must be met: (1) more than 10% of plasma cells in bone marrow aspirate, (2) paraprotein in serum or urine, and (3) osteolytic bone lesions or osteoporosis . However, these spots of bone destruction may also be seen in other conditions, especially in osseous metastases from solid cancers. Some radiological particularities that could be helpful for differential diagnosis have been reported by some authors. Indeed, bone destruction caused by cancer metastasis mostly involves the vertebral pedicles, whereas MM lesions are more commonly seen on the vertebral bodies and frequently involve the mandible and the distal axial skeleton . Moreover, the lytic bone lesions suggestive of MM are characteristically sharply defined and punched out with endosteal scalloping leading to a very typical “raindrop skull” appearance. In another study, Uygar et al.  compared the CT features of MM and osteolytic metastatic bone lesions and concluded that the presence of high density, lesional homogeneity, perilesional sclerosis, and marginal features could be used to distinguish metastatic from MM lesions. According to Lee et al.  magnetic resonance imaging (MRI) is useful in distinguishing MM from metastasis involving the spine; indeed, the salt and pepper infiltration pattern, the presence of more than five lesions within one vertebra, and the involvement of more than three consecutive vertebrae are highly suggestive of MM. However, they reported no significant differences in signal intensities or enhancement patterns. In conclusion, the authors argue for a high overlap between bone lytic lesions attributed to MM and those related to cancer metastases on radiologic investigations. In such a context, 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)-CT could be helpful in detecting not only bone metastatic lesions, but also primary solid tumors. In addition, some laboratory biomarkers are associated with solid cancers and could be an argument favoring cancers metastasis in difficult cases. Elevated CA 19-9, CEA, and AFP are more commonly associated with a gastrointestinal tumor; high levels of prostate-specific antigen (PSA) indicate prostate cancer. However, only biopsy with pathological examination could confirm the proper diagnosis.
In this case report, although lytic multiple lesions were first thought to be related to MM, the unusual findings of enlarged lymph nodes and elevated CA 19-9 made it necessary to consider the possibility of synchronous MM and solid tumor. Many papers have described synchronous solid tumors and MM mainly discovered on whole body scan. In this context, it is highly challenging to relate bone lytic lesions to either MM or tumor metastasis [3, 8,9,10,11,12,13].
However, to the best of the authors’ knowledge, only the case reported by Herrera et al. , involving MM and metastatic carcinoma affecting the same bone lesion, is similar to the present case. Pathological and immunohistochemical examinations are necessary to identify both components. Although the morphological examination could clearly distinguish carcinomatous cells from plasma cell proliferation, immunohistochemistry (IHC) is necessary to detect the tumor cells associated antigens. On IHC, pan-cytokeratin (AE1/AE3) and EMA positivity are consistent with the epithelial nature of the tumor cells. Other immunohistochemical markers, such as CK7, CK20, and organ-specific markers, are helpful to assess the primary origin of the disease. CD138 is a monoclonal anti‐syndecan‐1 antibody often used to identify plasma cells in the bone marrow of patients with MM. However, several carcinomas may also express CD138, including prostate, colon, renal cell, and hepatocellular carcinomas.
Distinguishing epithelial cells from plasma cells can easily be made based on microscopic examination. Indeed, epithelial cells tend to be larger with variable amounts of cytoplasm and marked nuclear atypia, and, as in the present case, mostly arranged on islands, nests, or glands with marked fibrous stromal reaction. However, plasma cells are smaller, with few amounts of cytoplasm, and they are mostly sparse. Moreover, MUM1, also known as interferon regulatory factor 4 (IRF4), is another interesting highly specific marker for normal and neoplastic plasma cells. It is classically negative on epithelial cells. In the present case, tumor cells showed (CK7+, CK20−, CK19+, CD138+) immunohistochemical profile. As presented above, CD138 is not specific and it may be expressed in various primary carcinomas. However, the most contributive marker is CK7. Hence, the immunohistochemical findings in the present case may be mainly seen in renal cell carcinomas, breast carcinomas, papillary thyroid carcinomas, lung adenocarcinomas, and biliary and pancreatic carcinomas . Less frequently, they may be seen in urothelial bladder carcinomas, gastric adenocarcinomas, and squamous cell carcinomas. IHC studies should therefore be always ordered in correlation with the clinical, radiological, and pathological findings. Indeed, immunohistochemical markers are not always specific and aberrant expression may be seen in various tumor cancers.
The etiopathogenesis of this reported association is not yet well established. Bone marrow reactive plasmacytosis occurs in a variety of diseases, including carcinomas, lymphoproliferative disorders, and inflammatory conditions, and hence could be a precursor for MM. Another possible theory is the disruption of the immune system secondary to the development of multiple myeloma, which could impair the immune surveillance and resistance to cancer cells .