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A 58-year-old man presents to the hospital in New York City with complaints of unbearable pain from a lump on his right buttock. He explains that the pain has been there for months, but over the past month the mass has grown and become increasingly painful, to the point that it is now interfering with activities, even walking and sitting. Over-the-counter ibuprofen has not helped relieve the pain, he adds.

He has no known medical comorbidities, although he does have a chronic persistent dry cough, which he assumes is due to smoking; he has a 40-pack-year smoking history. He says he is not coughing up blood and has no other generalized symptoms such as weight loss, night sweats, or chills.

Review of systems is significant for right upper-quadrant pain and lower back pain with paresthesia affecting both lower extremities.

Physical exam shows non-ulcerative and firm right inguinal lymphadenopathy and a right gluteal mass of approximately 10×5 cm, which is tender to palpation, discrete, firm, immobile, and non-erythematous.

Clinicians learn that the mass originally appeared 3-4 months previously as a small, painless lump, and has progressively worsened. The patient also has nail clubbing on both hands.

CT of the abdomen and pelvis with contrast reveals a solid right gluteal soft-tissue mass, destructive lesion of L1, bilateral adrenal and renal masses, intra-hepatic lesions, and pelvic soft tissue mass with slight ascites.

Based on their suspicion of metastatic disease, clinicians perform further imaging. CT of the head shows no mass lesions, and CT of the chest with contrast shows a poorly defined left upper-lobe mass measuring 10.3×7.9×9.3 cm with obstruction of left upper-lobe bronchus, and a small left pleural effusion.

Tests for tumor markers are negative for alpha-fetoprotein (AFP), carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), and prostate-specific antigen (PSA), although CA-125 is elevated at 176 U/mL.

Suspecting pneumonia, clinicians initiate treatment with antibiotics. They also perform ultrasound-guided biopsy of the gluteal mass, which finds poorly differentiated adenocarcinoma with features of tumor suggestive of primary lung cancer. Immunohistochemistry findings are positive for cytokeratin 7 (CK7) and thyroid transcription factor 1 (TTF-1), and negative for cytokeratin 20 (CK20), caudal type homeobox 2, CA19-9, napsin-A, and arginase-A antibodies.

The patient tells clinicians that he recently had a screening colonoscopy, which showed no evidence of pathology, but he had not undergone a prior low-dose CT chest scan for lung cancer screening.

He is discharged with recommendations for pulmonary and oncology outpatient follow-up, but he declines and opts instead for hospice care.

Discussion

Clinicians presenting this of a patient with a rare metastasis of lung cancer to soft tissue note that the case highlights the importance of high clinical suspicion and low threshold for biopsy, especially in high-risk patients presenting with new soft tissue lesions.

Notably, the authors write, approximately 70% of lung cancers have already metastasized at the time of initial presentation and diagnosis. One autopsy study reported the following sites for : liver (34.3%), adrenal glands (32.6%), bones (14.9%), central nervous system (12%), kidney (10.9%), myocardium (9.1%), pancreas (5.1%), spleen (4%), stomach (2.3%), small/large intestine (3.4%), thyroid (1.7%), and ovary (0.6%).

On the other hand, the reported overall prevalence of soft tissue metastasis -- i.e., involving cutaneous, subcutaneous, and skeletal muscle -- is only 2.3% among lung cancer patients.

The pathophysiology involves the lymphovascular, hematogenous, or direct extension of the primary tumor as a local or distant metastasis. The most common soft tissue sites of primary lung cancer metastases include the abdomen, chest, neck, and head. However, as the case authors explain, these lesions can appear anywhere, and they point to a case of a progressively worsening discrete painless nose tip lesion as well as an ulcerated wart-like hand lesion, due to primary squamous cell carcinoma.

Soft tissue metastasis typically occurs as a late presentation of the primary occult malignancy, the case authors add, noting that there is a 16-month average time between a lung cancer diagnosis and discovery of skin metastasis as reported in a 6-year study in which 10 of 4,385 lung cancer patients had cutaneous metastasis. Only very rarely do metastatic lesions present concurrently or even before lung cancer is diagnosed, the authors state.

The patient in this case had no known primary cancer; diagnostic tests included physical exam, tumor markers, and immunohistochemistry. Notable diagnostic features included the patient's bilateral , the most common paraneoplastic manifestation of primary lung cancer -- that malignancy, especially non-small cell lung cancer (NSCLC), accounts for approximately 90% of cases of digital clubbing.

Research has suggested that can also be helpful in identifying soft tissue metastases, which typically show lesions with poorly defined margins, low signal intensity on T1-weighted sequences, high signal intensity on T2-weighted sequences, and enhancement with gadolinium. Wide peritumoral enhancement with central necrosis is one of the main features of smoldering multiple myeloma, and is detectable in 92% of those patients.

The case authors note that their patient had elevated levels of CA-125, which is known to be associated with ovarian adenocarcinoma, and in more recent studies, has been identified in the peritoneum and pleural ectodermal cells. CA-125 has been associated with of lung cancer, and elevated levels have been observed in approximately 38% of lung cancer patients and 68% of those with advanced adenocarcinomas.

Histological and immunohistochemical analysis can also help establish a tumor's primary origin, with lung origin proven with positive CK7, TTF-1, and napsin-A staining pattern.

TFF-1, which is involved in regulating the expression of Clara cell secretory proteins and surfactant protein, plays an important role in primary lung adenocarcinoma, and both TFF-1 and napsin-A are highly sensitive and specific for detecting primary lung adenocarcinoma.

For example, in one study, TFF-1+/napsin-A+ staining was noted in 79% of 120 cases compared with only 8% of TFF-1–/napsin-A+ cases, and only 3% had TFF-1+/napsin-A–.

The case authors also cite research showing that an has high sensitivity and specificity for differentiating primary lung adenocarcinomas from extrapulmonary adenocarcinomas of breast or colon origin.

Another evaluation of the efficacy of immunohistochemical markers in subtyping poorly differentiated NSCLC found that 100% of biopsies of pulmonary adenocarcinoma expressed CK7, and 80% were positive for TTF-1, whereas p63 was extremely sensitive for pulmonary squamous cell carcinoma.

This case highlights the diagnostic and prognostic value of immunohistochemical testing. In the absence of a lung biopsy, the patient's smoking history, digital clubbing, and gluteal mass biopsy positive for TTF-1+CK7+CD20 panel were highly suggestive of primary pulmonary adenocarcinoma.

Generally, a good overall prognosis is seen in patients who are younger than 70, female, have well-differentiated tumors, and TFF-1 expression, while poor prognosis is associated with pre-treatment weight loss, current smoking, poor differentiation, advanced staging, and soft tissue metastasis.

Conclusion

The case authors conclude that new soft-tissue lesions -- which may be asymptomatic but generally present as a painful palpable mass -- warrant a high clinical suspicion of underlying malignancy. Given that the lesions provide accessible biopsy sites while avoiding invasive procedures, clinicians should observe a low threshold for biopsy, since missing such a diagnosis can be life-threatening.

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