Carcinoma of Unknown Primary



Carcinoma of Unknown Primary


Todd M. Blodgett, MD

Alex Ryan, MD

Hesham Amr, MD





Key Facts


Terminology



  • Metastatic cancer without known site of origin; histology inconsistent with known tumors from organ biopsied


Imaging Findings



  • Most common site: Upper aerodigestive tract, specifically lung


  • Gastrointestinal and urogenital tract also common


  • Squamous cell: Primary most often in tonsils, nasopharynx


  • Adenocarcinoma: Primary most often in thorax, GI tract, urogenital tract


  • Likelihood of primary detection with PET/CT: 25-40%; CT: 25%


  • FDG PET provides whole-body survey


  • PET may commonly reveal “missed primary” rather than unknown primary in true sense, i.e., following complete work-up


  • Small study showed PET/CT more sensitive than PET alone, with 53% detection rate for occult cancers missed by other techniques


Top Differential Diagnoses



  • Physiologic Activity


  • Inflammation


  • Infection


Diagnostic Checklist



  • In patient with CUP, perform conventional laboratory workup and combination of imaging studies, with consideration of PET/CT






Axial CECT shows a complex cystic left renal mass suggestive of renal cell carcinoma image in this patient with a brain metastasis and no primary.






Axial fused PET/CT shows mildly increased FDG activity corresponding to the mural nodularity image, confirmed to be renal cell carcinoma.


TERMINOLOGY


Abbreviations and Synonyms



  • Carcinoma of unknown primary (CUP)


  • Includes undifferentiated carcinomas in addition to adenocarcinoma


Definitions



  • Metastatic cancer without known site of origin



    • Histology inconsistent with known tumors from organ biopsied


  • Also defined as presence of metastatic disease for which site of primary lesion remains unidentified



    • Remains unknown despite review of



      • Medical history


      • Physical exam


      • Lab work (CBC, kidney/liver/pancreas function tests, PSA, U/A)


    • Imaging evaluation usually includes CXR, abdominopelvic CT, mammography


    • After common imaging investigation, 20-27% of primaries remain unidentified


IMAGING FINDINGS


General Features



  • Best diagnostic clue: Detection of focal intense FDG activity in potential primary organ or site in patient with biopsy-proven carcinoma of unknown primary


  • Location



    • Most common site: Upper aerodigestive tract, specifically lung



      • May also have abnormal mediastinal nodes


      • Consider accessible areas for subsequent confirmatory biopsy


    • Gastrointestinal and urogenital tract also common



      • Appear as focal areas of intense FDG activity in bowel rather than linear areas of physiologic activity


      • Look carefully at kidneys as a small renal cell carcinoma may be missed or obscured by physiologic excretory FDG activity


    • Frequency of metastases by location



      • Lymph node (LN) 46.3%


      • Liver 12%


      • Brain 11%



      • Bone 11%


      • Lung 6%


      • Pleura 4%


      • Peritoneum 4%


      • Other 10%


    • Involvement of supraclavicular and low cervical lymph nodes may be suspicious for primary in chest or abdomen



      • Associated with poorer prognosis than metastases of upper neck levels


    • Squamous cell



      • Primary most often in tonsils &/or nasopharynx


      • Look for asymmetrical focal intense FDG activity on PET and PET/CT


    • Adenocarcinoma



      • Primary most often in thorax, GI tract, or urogenital tract


  • Size: Varies from small (< 1 cm) to several centimeters


  • Morphology: Range of morphologies, including no obvious findings on CT to a several centimeter mass


Imaging Recommendations



  • Best imaging tool



    • Likelihood of primary detection with PET/CT: 25-40%; CT: 25%


    • FDG PET provides whole-body survey


    • Patients with head/neck mets of non-SCCA histology should not be limited to imaging of head/neck area only



      • Whole-body imaging has been proven beneficial


    • Typical workup for patients with SCCA lymph node mets



      • Thorough physical exam including transnasal fibre-endoscopy of nasal cavity, nasopharynx, oropharynx, hypopharynx, larynx


      • CECT or CEMR of neck and PA/Lat CXR


      • Panendoscopy includes rigid esophagoscopy, tracheobronchoscopy, hypopharyngoscopy, laryngoscopy


      • Inspection/palpation of oropharynx and oral cavity, with biopsies taken from suspicious mucosal areas


      • Ipsilateral tonsillectomy if no primary detected during panendoscopic random biopsies


      • FDG PET often used when all of the above approaches have failed; may also direct biopsies


      • Non-SCCA histology has similar workup, with CT of chest and abdomen along with pelvic/prostate examinations


    • Mammography very low yield; rarely do patients with CUP have primary mass in breast


  • Protocol advice



    • Consider PET/CT evaluation, although currently not routinely used for CUP


    • Contrast-enhanced CT may provide additional benefit



      • Better characterization of focal areas of FDG activity


      • Differentiation of potential bowel lesion from those adjacent to bowel


CT Findings



  • CT typically used to help identify primary



    • Low sensitivity (˜ 25%)


  • CT scanning is the imaging modality of choice in terms of availability, cost effectiveness, quickness, and patient compliance



    • Especially for evaluation of cervical lymphadenopathy and identification of occult primary lesions


  • Newer technology and methods of acquisition



    • Better image quality and resolution


    • Better reconstructive capabilities


    • Quicker scans


    • Decreased artifact


  • Quicker scans also allow dynamic maneuvers to be used



    • Puffed cheek and modified Valsalva techniques can help open opposed mucosal surfaces in the oral cavity, oropharynx, and hypopharynx



      • May allow easier detection of unknown mucosal primaries



    • Nonetheless, critical evaluation of the CT scan helps direct biopsies during panendoscopy in the workup of the unknown primary tumor


  • For evaluation of cervical lymphadenopathy, a CT scan of the neck is helpful to assess the involvement of vital structures



    • Also provides the clinician with useful data regarding surgical resectability


  • CT scan can also be used to evaluate clinically negative cervical lymph node zones


  • Radiographic criteria of potential pathological lymph nodes



    • Rounding of the lymph node


    • Size > 1.5 cm in the jugulodigastric region or > 1 cm in other regions


    • Hypodense fluid center of the lymph node that signifies necrosis


    • Mass effect


Nuclear Medicine Findings



  • PET



    • FDG PET shown to identify lesion in ˜ 25-40% of patients with negative conventional imaging investigations


    • PET may commonly reveal “missed primary”



      • Rather than unknown primary in true sense, i.e., following complete workup


    • False negative may result from



      • Low tumor uptake (e.g., carcinoid) or high background uptake (e.g., liver, high serum glucose level)


    • PET has high specificity for tumors in lung, breast, and pancreas


  • Possibly low clinical impact of FDG PET in patients who have already undergone extensive workup with panendoscopy


  • Small study showed PET/CT more sensitive than PET alone, with 53% detection rate for occult cancers missed by other techniques


  • Criteria for malignancy on FDG PET or PET/CT



    • FDG hypermetabolism at site of pathological changes on CT


    • Marked focal hypermetabolism at sites suggestive of malignancy (liver parenchyma, bone marrow)



      • Despite absence of signs of pathology at those sites on CT


  • Identification of primary is more complex than identification of metastatic lesions



    • Patient’s history is often helpful


    • Distribution of pathological lesion may be helpful



      • Knowledge of the pattern of spread of different tumors


    • More difficult in cases of generalized disease with many foci in different organs


    • If unable to identify a lesion as the site of primary, may conclude that CUP syndrome was generalized


    • Rate of detection of malignancy in general will be higher than that of primary


DIFFERENTIAL DIAGNOSIS


Physiologic Activity



  • Following structures commonly have increased physiologic activity that may mimic that of malignancy



    • Colon: Can be focal, short segment, or linear


    • Cardiac: Usually left ventricular, though all chambers may have increased wall activity in pathologic states


    • Thymus: Seen in younger patients, usually linear if physiologic


    • Glands: Look for symmetry to differentiate physiologic from pathologic activity


    • Lymphoid tissue: May be asymmetrical or symmetrical


    • Muscle: Often linear, helping to establish as physiologic; when focal can look like malignancy; correlate with CT


    • Brown fat: CT showing fat attenuation is diagnostic


  • PET/CT helps facilitate differentiation of pathologic from physiologic FDG activity


Inflammation



  • Several inflammatory or granulomatous conditions, such as sarcoidosis, may cause focal FDG activity and mimic malignancy


Infection



  • Infectious processes such as underlying fungal infection or TB may cause focal activity


  • Dental abscesses may cause focal intense FDG activity, mimicking head and neck cancer


Benign Lesion



  • Colonic adenomas and thyroid adenomas may have focal FDG activity


  • Benign osseous lesions include fibrous cortical defect, osteoradionecrosis, and Paget

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Sep 22, 2016 | Posted by in MAGNETIC RESONANCE IMAGING | Comments Off on Carcinoma of Unknown Primary

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