Cancer of unknown primary: Ancillary testing of cytologic and small biopsy specimens in the era of targeted therapy

Abstract

Initial evaluation of patients presenting with a suspected malignancy without a clear clinical or radiologic impression of a primary site (so-called cancer of unknown primary, or CUP) frequently includes fine needle aspiration (FNA) to both establish a diagnosis and procure tissue for additional studies. Careful management of limited specimen material is especially important in the modern era, when molecular studies may take precedence over a more definitive tissue diagnosis. This review summarizes our practice habits when encountering a CUP. Broadly, key morphologic patterns in context of patient history and clinical-radiologic impression should guide the selection of a limited panel of IPOX stains to establish first a broad lineage. Subsequently 1-2 site-specific markers may be used to confirm the diagnosis. In difficult cases, it is helpful to convey the situation to the treating physicians, who may prefer to prioritize molecular testing over pursuit of a more definitive diagnosis. Prudent choice of immunoperoxidase (IPOX) studies, based on both key cytomorphologic criteria and continued communications with the clinical team regarding their needs for treatment planning, is critical in CUP cases.

Immunocytochemistry for diagnostic cytopathology—A practical guide

“…Metastases are commonly observed in effusions, lymph nodes, liver, lung and bones, among others; the majority are caused by carcinomas, mainly adenocarcinomas 243–245 . Work‐up of metastases should be tailored to the patient's history, gender, and location of metastases along with a review of prior pathologic material and imaging (if available).…”

“…Work‐up of metastases should be tailored to the patient's history, gender, and location of metastases along with a review of prior pathologic material and imaging (if available). ICC remains the most cost‐effective method of determining the type of malignancy and site of origin 243–245 (Figure 9).…”

“…Use of different keratins can narrow down the differential diagnosis 246,247 (Table 12). Additional ICC may be needed; the most commonly used first‐line markers for identification of the primary site are listed in Table 13 162,244,245,248 …”