Beyond the Abstract - A diagnostic dilemma: Metastatic testicular cancer and systemic sarcoidosis - a review of the literature, by Viplove Senadhi, MD., and Rajeev Gupta, MD

BERKELEY, CA ( - We describe the case of a 30-year-old African-American male who presented with complaints of a headache, skin lesions, and a scrotal mass. A computed tomography (CT) scan of the head showed lesions in the frontotemporal and pons region, causing obstructive hydrocephalus.

A CT of the chest did not reveal any hilar/mediastinal lymphadenopathy or evidence of sarcoidosis, and a CT of the abdomen/pelvis demonstrated a hydrocele with a right hemiscrotal mass without any lymphadenopathy. An ultrasound of the scrotum showed an enlarged epididymis bilaterally as well as a solid hypoechoic ill-defined mass on the right side:


separate from the intact testis. Laboratory work-up for testicular malignancy revealed normal human chorionic gonadotropin (HCG), LDH and alpha fetoprotein (AFP) levels. Given the high suspicion for testicular malignancy with brain metastasis, a right orchiectomy was completed. The pathology revealed non-caseating necrotizing granulomas that stained negative for tubercular and fungal organisms, which was consistent with sarcoidosis:

Additionally, the patient’s skin and central nervous system (CNS) lesions improved on steroids that had been initiated for cerebral edema.

Sarcoidosis is a multisystem disease that most commonly involves the lungs and the lymph nodes; but with genitourinary tract involvement, can easily mimic testicular cancer with nodal involvement and metastasis to the lungs. To further confound the differentiation, testicular cancer metastasis to the lungs is the most common parenchymal organ to be involved in metastatic testicular lesions, which is difficult to distinguish from pulmonary sarcoidosis independent of an invasive biopsy. Furthermore, given the predilection of testicular cancer for CNS metastasis, neurosarcoidosis can also be mistaken for testicular cancer metastasis to the CNS, as seen in our case. In terms of the epidemiology of scrotal swelling or a scrotal mass in young males, testicular malignancy is the leading differential that must be ruled out and is the most common tumor in males under the age of 35. Interestingly, genitourinary sarcoidosis is also likely to present in this same population. There are reported cases where systemic sarcoidosis has been interpreted as metastatic testicular cancer, leading to inadvertent chemotherapy as well as orchiectomy (as in our case). It is also critical to distinguish sarcoidosis from testicular cancer early on, as testicular cancer requires aggressive surgery and systemic chemotherapy. On the other hand, sarcoidosis can be simply treated with a course of corticosteroids and fertility preserving, which is a vast difference from the standard of care in testicular cancer.

Thus, how can testicular cancer be differentiated from sarcoidosis? There are subtleties that help distinguish the two from each other epidemiologically, serologically, and pathologically. Generally, testicular cancer affects Caucasian males while sarcoidosis is more common among African-American males. However, the rates of testicular cancers are rising in African-American males. The imaging modalities in evaluating testicular masses (ultrasound) can be helpful in differentiating sarcoidosis from testicular cancer, but often times, it is unrevealing (as seen in our patient). Serum markers can also be extremely helpful in the differentiation between these two conditions, as the serum angiotensin-converting enzyme (ACE) is elevated in 75% of untreated active sarcoidosis patients, but not in patients with testicular cancer. Additionally, in non-seminoma testicular cancers, serum AFP and beta-HCG (B-HCG) levels are elevated in approximately 50% of patients. Lastly, pathology of an extratesticular lesion may be very useful in differentiation. Biopsy of skin lesions in sarcoidosis or endoscopic ultrasound biopsies of mediastinal lymph nodes can reveal a more definitive diagnosis. In our patient, corticosteroids, originally started to decrease cerebral edema due to supposed testicular cancer metastasis, subsequently shrunk the CNS lesions. Unfortunately, this occurred after the orchiectomy. A trial of corticosteroids should be strongly considered in unequivocal cases in an effort to avoid an unnecessary orchiectomy, as sarcoid lesions will regress with corticosteroid treatment.

A final differentiating feature would be that metastatic testicular cancer almost always has a favorable response to chemotherapy with the exception being non-pulmonary metastasis. On the other hand, chemotherapy can cause severe exacerbations in active sarcoidosis and can precipitate acute exacerbations of undiagnosed subclinical sarcoidosis. Systemic chemotherapy given for a misdiagnosis of metastatic testicular cancer will mimic chemoresistant testicular cancer, when in reality, underlying sarcoidosis was exacerbated.

There is also an association between testicular cancer and sarcoidosis, which seems to be not well known to most health care providers. A review of the literature performed by Paparel, a urologist at the Memorial Sloan-Kettering Cancer Center, and his colleagues noted that there was a coexistence of sarcoidosis or a sarcoid-like reaction in patients with testicular cancer. In half of the cases where testicular cancer and sarcoidosis coexisted, testicular cancer was diagnosed prior to sarcoidosis. Thirty-one percent of cases of testicular cancer that coexisted with sarcoidosis were diagnosed simultaneously. Sarcoidosis was associated with different types of testicular cancer, with seminoma being the most common. In 80% of these cases with concomitant sarcoidosis, the sarcoidosis regressed simultaneously. The coexistence of sarcoidosis and testicular cancer did not change the management of testicular cancer or the overall prognosis. With reference to the aforementioned, the dilemma arises in cases where a false diagnosis of testicular cancer is made, when, in fact, sarcoidosis is the correct diagnosis, as seen in our patient. However, given this strong association between sarcoidosis and testicular cancer, it is noted that long-term monitoring and follow-up in the context of a high clinical suspicion may be necessary in patients afflicted with either condition.

In conclusion, differentiating testicular cancer from genitourinary sarcoidosis is difficult, but can be clarified using a combination of clinical presentations, epidemiology, serum markers (ACE, AFP, B-HCG), biopsies from skin/lymph nodes, imaging, a corticosteroid trial, and in the context of chemotherapy response or provocation. It is critical to differentiate genitourinary sarcoidosis from malignancy, as a misdiagnosis can lead to unnecessary surgical interventions, which have important implications for future fertility. There can also be a coexistence of, as well as an association between testicular cancer and sarcoidosis, which should be recognized by health care providers and may necessitate monitoring patients with either condition.


  1. Gupta R., Senadhi V* A Diagnostic Dilemma: Metastatic Testicular Cancer and Sarcoidosis: A Review of the Literature Case Reports in Oncology 2011 March;4: 118-124 Publication Status: Cited in PubMed and PubMed Central. PubMed ID 21519812
  2. Senadhi V., Dutta S. Testicular Seminoma Metastasis to the Gastrointestinal Tract and the Necessity of Surgery. Journal of Gastrointestinal Cancer April 26th, 2011 Vol. 42 No. 2: Cited in PubMed. PubMed ID 21519812

Acknowledgements: Dr. Rajeev Gupta, co-author and colleague, whose efforts and determination will serve him well in Pulmonary and Critical Care Medicine.

Written by:
Viplove Senadhi, MD., and Rajeev Gupta, MD. as part of Beyond the Abstract on This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

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