Reply to: Metastasis to left scapula with unknown primary: Approach to pathological diagnosis.

Sir,

In a recent issue, an interesting case titled “Metastasis to left scapula with unknown primary: Approach to pathological diagnosis” was published by Shiasta et al.[1] In this case, the final diagnosis was given as metastatic adenocarcinoma, probably arising from the lungs. The majority of metastatic carcinomas of unknown primaries (MCUPs) in adults are adenocarcinomas and undifferentiated carcinomas, but the relative number of each differs depending on age and sex.[2] Huebner et al., in a case study of a series of 343 patients found that 40% of the metastatic tumors were adenocarcinoma, 28% were undifferentiated carcinoma, 14% were squamous cell carcinoma, and the remainder were poorly differentiated tumors.[3] Patients with visceral metastasis of carcinoma below the diaphragm had a poor prognosis and responded poorly to chemotherapy.[4]

It is also important to identify carcinomas that can be treated by chemotherapy or hormonal manipulation or both, especially metastasis from breast and prostate.[5] For the final diagnosis, analysis of immunohistochemical (IHC) markers are of utmost importance. Therefore, treatment should be started from the lung and breast, depending on the gender.[5] To rule out lung adenocarcinoma, IHC panel of CK 7, CK 14, CK 20, and TTF-1 is very important. Because some mucinous adenocarcinomas are CK 20 positive, staining with mucicarmine may be fruitful. However, in the published case, CK 20 was negative. CK 20 positivity is extensively reported in colorectal cancer; in such a case, high resolution computed tomography can give better result than ultrasonography. In the published case, routine hematoxylin and eosin staining gave impression of paraganglionoma that has been ruled out by IHC. The expression of CK7 and CK20 is distinctive to glandular epithelia. This may include tumors like colorectal, pancreatic, or bronchoalveolar adenocarcinomas, as well as adenocarcinomas of the salivary glands.[6] TTF-1 is a nuclear tissue-specific protein transcription factor, found only in thyroid/thyroid tumors regardless of histological types, as well as in adenocarcinomas (75%), non-small cell carcinomas (63%), and small cell carcinomas (90%) of the lung.[78] Therefore, in the present case, TTF-1 staining would have given evidence in favor of lung adenocarcinoma. It has been noted in previous studies that no lung adenocarcinomas were CK20 positive, but almost all were CK7 positive, and 70% of the cases were TTF-1 positive.[9] Although salivary gland adenocarcinoma rarely metastasizes and is clinically evident, it should be included in differential diagnosis. Because rapid metastasis of salivary gland adenocarcinoma into the lung, brain, and multiple osseous site has been reported in literature.[1011] Here, staining with CK 7/14 and TTF-1 is useful. Salivary adenocarcinomas are positive for CK 7/14, negative for TTF-1, and negative for CK 20.[6] In conclusion, IHC markers with advanced radiological investigations are mainstay in the diagnosis of occult or unknown primaries.