Carcinoma of unknown primary

Etoposide causes multiple DNA double-strand breaks by inhibiting topoisomerase II. The pharmacokinetics of etoposide are described by a two-compartment model, with an a half-life of 0.5 to 1 hour and a (5 half-life of 3.4 to 8.3 hours. Approximately 30% of the dose is excreted unchanged by the kidney.16 Etoposide has shown activity in the treatment of several types of lymphoma, testicular and lung cancer, retinoblastoma, and carcinoma of unknown primary. The intravenous preparation has limited stability, so final concentrations should be 0.4 mg/mL. Intravenous administration needs to be slow to prevent hypotension. Oral bioavailability is approximately 50%, so oral dosages are approximate two times those of intravenous doses however, relatively low oral daily dosages are used for 1 to 2 weeks. Side effects include mucositis, myelosuppression, alopecia, phlebitis, hypersensitivity reactions, and secondary leukemias. 

In this chapter the role of diagnostic IHC in diagnosing CUPS is emphasized, especially as it relates to adeno-carcinoma/poorly differentiated carcinoma of unknown primary site and germ cell tumors, which account for more than 90% cases of CUPS. Specific tables that aid in the differential diagnosis of tumors in specific anatomic sites are presented. The role of molecular studies in combination with IHC for patients with CUPS has been discussed. 

Greco FA, Burris 3rd HA, Erland JB, et al. Carcinoma of unknown primary site. Cancer. 2000 89 2655-2660. 

Greco FA, Hainsworth JD. The management of patients with adenocarcinoma and poorly differentiated carcinoma of unknown primary site. Semin Oncol. 1989 16 116-122. 

Hainsworth JD, Greco FA. Managing carcinomas of unknown primary site. Oncology (Williston Park). 1988 2 43-49. 

Hainsworth JD, Wright EP, Johnson DH, et al. Poorly differentiated carcinoma of unknown primary site clinical usefulness of immunoperoxidase staining./ Clin Oncol. 1991 9 1931-1938. 

Rubin BP, Skarin AT, Pisick E, et al. Use of cytokeratins 7 and 20 in determining the origin of metastatic carcinoma of unknown primary, with special emphasis on lung cancer. Eur J Cancer Prev. 2001 10 77-82. 

Important characteristics of carcinoma as it relates to the CNS and meninges are its distinctively epithelial structure (Fig. 20.58A see Table 20.6) and the overwhelming predominance of metastatic over primary carcinomas. Metastatic carcinomas are described in detail in Chapter 8, Immunohistology of Metastatic Carcinomas of Unknown Primary. Rare primary brain carcinomas occur in the choroid plexus, from germ cell tumors of the pineal and suprasellar regions, and from cysts. 725 section emphasizes how to distinguish between carcinomas (see Fig. 20.58B to D) and various primary intracranial tumors (see Box 20.2). 

Carcinoma of unknown primary (CUP) accounts for 3% to 5% of all solid malignancies. The scenarios of CUP presentation are as follows ... 

FIGURE 21.18 Carcinoma of unknown primary (A, B). Tumor cells in the pericardial fluid (C). TTF-1 demonstrates a strong nuclear staining (D). Chromogranin is expressed strongly in tumor cells, confirming pulmonary origin, in particular a small cell type. 

Pomjanski N, Grote HJ, Doganay P, et al. Immunocytochemical identification of carcinomas of unknown primary in serous effusions. Diagn Cytopathol. 2005 33 309-315. 

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