What are the next steps in managing a psoas mass with positive Cytokeratin 7 (CK7) staining?

Management of a Psoas Mass with Positive CK7 Staining

A psoas mass with positive CK7 requires immediate expanded immunohistochemical workup to identify the primary site, as CK7 positivity alone is non-specific and consistent with multiple possible origins including renal cell carcinoma (chromophobe subtype), urothelial carcinoma, pancreaticobiliary adenocarcinoma, ovarian/endometrial carcinoma in females, and lung adenocarcinoma. 1

Immediate Next-Step Immunohistochemistry Panel

The diagnostic workup must include a structured immunohistochemical approach:

First-Line Priority Markers

• CK20 staining is essential to establish the CK7/CK20 phenotype, which narrows the differential diagnosis significantly 2
• PAX8 must be performed immediately to evaluate for renal cell carcinoma or Müllerian origin (ovarian/endometrial), as PAX8 is highly sensitive for these primaries 2
• TTF-1 is mandatory to exclude lung adenocarcinoma, as most lung carcinomas are TTF-1 positive 2
• GATA3 (in females) screens for breast and urothelial carcinoma, both of which commonly present as retroperitoneal masses 1
• Uroplakin III and p63 should be added if urothelial carcinoma is suspected, as upper tract urothelial carcinoma can present as a psoas mass 2

Critical Renal Cell Carcinoma Markers

Chromophobe RCC is a leading consideration for a psoas mass with CK7 positivity, as chromophobe RCCs show diffuse CK7 positivity in contrast to oncocytomas which are CK7-negative or focally positive. 2 Additional markers include:

• Carbonic anhydrase IX (CAIX) to distinguish clear cell RCC (diffusely positive) from chromophobe RCC (negative) 2
• CD117 (c-kit) is typically positive in chromophobe RCC 2
• Vimentin is usually negative in chromophobe RCC but positive in clear cell RCC 2

Gender-Specific Considerations

For female patients, the workup must include:

• ER/PR (estrogen/progesterone receptors) to exclude breast carcinoma, which is CK7+ in 98% of cases 1
• SOX10 for triple-negative breast cancer evaluation 1
• WT1 to evaluate for ovarian serous carcinoma, as WT1 is positive in almost all ovarian serous carcinomas 2

For male patients:

• PSA and PSMA are mandatory to exclude prostate adenocarcinoma, which can present as retroperitoneal masses 2

Mandatory Clinical and Imaging Workup

Imaging Studies

• CT scan of chest, abdomen, and pelvis with contrast is the baseline requirement for all patients with a psoas mass to identify the primary site and assess for metastatic disease 2, 1
• Dedicated renal protocol CT or MRI should be performed if renal cell carcinoma is suspected based on imaging characteristics or immunoprofile 2
• Cystoscopy with retrograde pyelography is indicated if urothelial carcinoma is in the differential, particularly if the mass involves the ureter or renal pelvis 2
• FDG-PET scan may be considered if the primary site remains occult after initial workup, though it is not standard for renal cell carcinoma staging 2

Laboratory Studies

• Serum creatinine and renal function tests to assess baseline kidney function 2
• Urine cytology if urothelial carcinoma is suspected 2
• Serum AFP and beta-hCG in younger patients (<40 years) to exclude germ cell tumors 2

Interpretation of CK7/CK20 Phenotypes

The CK7/CK20 pattern guides the differential diagnosis:

• CK7+/CK20-: Most consistent with lung, breast, thyroid, pancreatic, ovarian, endometrial, gastric, urothelial, or endocervical carcinomas, as well as chromophobe RCC 2
• CK7+/CK20+: Suggests urothelial carcinoma (bladder or upper tract), pancreaticobiliary adenocarcinoma, or gastric carcinoma 2, 3
• CK7+/CK20- with PAX8+: Highly suggestive of renal cell carcinoma (chromophobe or papillary type) or Müllerian origin 2

Treatment Approach Based on Primary Site Identification

If Renal Cell Carcinoma is Confirmed

• Surgical resection with nephrectomy is the primary treatment if the tumor is localized, with consideration for nephron-sparing approaches in select cases 2
• Regional lymphadenectomy should be performed for high-grade tumors 2
• Systemic therapy with VEGF-targeted agents or immune checkpoint inhibitors is indicated for metastatic disease 2

If Urothelial Carcinoma is Confirmed

• Nephroureterectomy with bladder cuff excision is standard for upper tract urothelial carcinoma involving the renal pelvis or ureter 2, 4
• Cisplatin-based chemotherapy should be considered in the neoadjuvant or adjuvant setting for muscle-invasive disease 4

If Primary Site Remains Occult

• Empiric platinum-based chemotherapy (paclitaxel 200 mg/m² + carboplatin AUC=6 every 3 weeks) is the standard treatment for adenocarcinoma of unknown primary with unfavorable features 1
• Site-specific therapy should be administered if additional immunohistochemistry and clinical correlation identify a likely primary 1

Critical Pitfalls to Avoid

• Do not assume CK7 negativity rules out colorectal origin, as 17.3% of colorectal carcinomas express CK7, particularly high-grade tumors and those with lymph node metastasis 5
• Do not rely on CK20 negativity to exclude colorectal carcinoma, as 18.9% of colorectal carcinomas are CK20-negative 5
• Chromophobe RCC can be misdiagnosed as oncocytoma without CK7 staining, as chromophobe RCC shows diffuse CK7 positivity while oncocytoma is CK7-negative or focally positive 2
• Urothelial carcinoma metastases maintain concordant CK7/CK20 expression with the primary tumor, so positive CK7 in a psoas mass is consistent with upper tract urothelial carcinoma if the primary is also CK7+ 3

Prognostic Considerations

• Performance status is the most important factor determining treatment candidacy—only patients with ECOG PS 0-2 should receive chemotherapy 1
• Median survival for adenocarcinoma of unknown primary with unfavorable features (multiple organ metastases) is approximately 3 months without treatment, with 1-year survival <20% 1
• Extranodal disease (liver, lung, bone metastases) carries significantly worse prognosis than lymph node-only disease 1