What is the workup for suspected malignancy?

Workup for Suspected Malignancy

The workup for suspected malignancy should begin with location-specific imaging (ultrasound for abdominal/pelvic masses, plain radiographs for bone lesions, chest CT for pulmonary lesions) followed by cross-sectional imaging (CT or MRI), appropriate laboratory studies including tumor markers, and tissue diagnosis via core needle or excisional biopsy when indicated. 1, 2

Initial Assessment by Location

Abdominal/Pelvic Mass

• Ultrasound is the first-line imaging modality to determine if the mass is solid or cystic and assess vascularity 1
• CT abdomen/pelvis with IV contrast should follow for suspected malignancy or indeterminate ultrasound findings, providing detailed characterization and assessment for metastasis 1
• For pelvic/adnexal masses specifically, transvaginal and transabdominal ultrasound with Doppler is preferred initially 1
• MRI pelvis without and with IV contrast is superior for characterizing complex adnexal masses when ultrasound is indeterminate 1

Bone Lesions

• Plain radiographs are the initial study when a bone tumor is suspected 2
• In patients under 40 years with an aggressive, painful bone lesion, refer to an orthopedic oncologist before further workup due to high risk of primary bone malignancy 2
• In patients ≥40 years, if radiographs don't suggest a specific diagnosis, obtain chest/abdomen/pelvis CT, bone scan, mammogram, and other imaging as clinically indicated 2
• Complete staging before biopsy includes chest imaging (chest radiograph or CT), MRI for local staging, CT of primary site, and bone scan 2

Bladder/Urothelial Lesions

• Cystoscopy with transurethral resection (TURBT) is the initial diagnostic and staging procedure 2
• Examination under anesthesia (EUA) should be performed 2
• CT or MRI of abdomen/pelvis to assess local and regional extent, though these cannot accurately predict depth of invasion 2
• Chest imaging (radiograph or CT) to detect metastases 2
• Bone scan only in patients with symptoms or elevated alkaline phosphatase 2

Hepatic Lesions

• Multiphasic CT or MRI showing classic enhancement pattern is more definitive than AFP alone for HCC diagnosis 2
• If rising AFP without visible mass, additional imaging (CT or MRI) is recommended 2
• Biopsy may be considered when lesion is suspicious but imaging doesn't meet HCC criteria 2

Laboratory Studies

General Malignancy Workup

• Complete blood count (CBC) to assess for anemia, leukocytosis, thrombocytosis, or thrombocytopenia 2, 3, 4
• Comprehensive metabolic panel including liver function tests (bilirubin, AST, ALT, alkaline phosphatase), renal function (BUN, creatinine), and albumin 2, 3
• Lactate dehydrogenase (LDH) - elevated in various malignancies including bone tumors, lymphomas, and germ cell tumors 2, 3

Location-Specific Tumor Markers

For Pelvic/Adnexal Masses:

• CA-125 is recommended as part of initial evaluation to differentiate benign from malignant processes 3
• Age-specific markers for patients <35 years: AFP and hCG to assess for germ cell tumors and rule out pregnancy 3
• Inhibin if granulosa cell tumor suspected 3
• CEA for suspected mucinous histology, with gastrointestinal tract evaluation to distinguish primary ovarian from metastatic disease 3

For Hepatobiliary Malignancy:

• AFP testing useful in conjunction with imaging, though can be elevated in pregnancy and other cancers (cholangiocarcinoma, colon metastases, lymphoma, germ cell tumors) 2
• Hepatitis panel: HBsAg, hepatitis B surface antibody, HBcAb, HBcAb IgM (if acute hepatitis), HCV antibodies 2
• Confirm viral load if positive for HBsAg, HBcAb IgG, or HCV antibodies 2

For Bone Tumors:

• Alkaline phosphatase (ALP) - commonly elevated in bone malignancies 2

Lymphoma-Specific Workup

• LDH and β2-microglobulin for prognostication 2
• HIV and hepatitis B/C screening 2
• Immunophenotyping of peripheral blood and bone marrow is not routinely recommended 2

Tissue Diagnosis

Biopsy Principles

• Image-guided core needle biopsy is preferred for suspicious solid masses 1
• Excisional lymph node biopsy or core biopsy should be performed for lymphoma diagnosis; fine-needle aspiration is insufficient 2
• For bone lesions, the biopsy tract must be planned to lie within the planned resection bed so it can be resected with wide margins during definitive surgery 2
• Fine-needle aspiration should be avoided for suspected ovarian masses to prevent spillage of malignant cells 1
• For bone tumors, appropriate communication between surgeon, musculoskeletal oncologist, and bone pathologist is critical in planning biopsy route 2

Common Pitfall

Do not perform fine-needle aspiration for primary bone lesions - diagnostic accuracy is less than core needle or open biopsy, though it doesn't carry significant risk of tumor seeding 2

Staging and Metastatic Evaluation

Chest Imaging

• Chest radiograph or chest CT to detect pulmonary metastases is standard for most malignancies 2

Bone Scan

• Indicated for patients with bone pain, elevated alkaline phosphatase, or clinical suspicion of bone metastasis 2
• Not routinely needed in asymptomatic patients without these findings 2

Advanced Imaging

• Whole-body MRI is sensitive for detecting skeletal metastases in small cell neoplasms, Ewing sarcoma, and osteosarcoma 2
• PET or PET/CT useful for evaluating chemotherapy response in osteosarcoma, Ewing sarcoma, and advanced chordoma 2

Critical Pitfalls to Avoid

• Do not rely solely on CA-125 for ovarian cancer diagnosis - it can be elevated in benign conditions and may not be elevated in early-stage disease 3
• Do not skip age-appropriate tumor markers in young patients - missing AFP/hCG in patients <35 can lead to missed germ cell tumor diagnoses 3
• Do not perform biopsy before complete staging in bone sarcomas - staging must be completed first 2
• Do not assume negative biopsy rules out malignancy in a growing mass - continual monitoring with multidisciplinary review is essential 2
• For mucinous pelvic masses, always evaluate the gastrointestinal tract to avoid misdiagnosing metastatic disease as primary ovarian cancer 3