53 year old man with a 3 year history of progressive supranuclear palsy who first noted a left arm subcutaneous nodule in the left axilla.

Treatment History:

  • 2/2/11 Left axillary mass incisional biopsy. Pathology: carcinoma with neuroendocrine differentiation (small blue cells); no clear lymph node architecture was identified making it unclear whether this represented a primary tumor or lymph node metastasis.
  • 2/23/11 CT chest, abdomen and pelvis: 12.1 cm left axillary mass; 4 spleen lesions
  • 3/1/11 MRI left shoulder: 17 cm mass compressing the subclavian vein and abutting the brachial plexus
  • 3/25/11 Radiation therapy to left axillary mass (4400 cGy with 2800 cGy boost)
  • 3/30/11 Brain MRI: negative
  • 4/4/11 MRI of abdomen: 5 spleen lesions, largest measuring 4.9 cm
  • 4/20/11 CT abdomen performed in the setting of acute abdominal pain: progressing spleen lesions, with one that had ruptured the splenic capsule causing intra-abdominal hemorrhage
  • 5/11 Initiated cisplatin and etoposide
  • 7/29/11 CT chest, abdomen and pelvis: spiculated nodules in the left upper lobe of the lung, right lung clear; left axillary adenopathy (largest node 3.0 cm); decrease in the size of previously noted spleen lesions; 2.3 cm retroperitoneal lymph node; 2.1 cm perisplenic lymph node; largest spleen lesion 6.0 cm
  • 8/16/11 MRI of spine: previously known compression fractures identified, but no clear evidence of metastatic disease and no evidence of cord compression
  • 8/17/11 Bone scan: uptake in skull, rib, both femurs and pelvis
  • Currently, the patient reports back pain.

  • Past medical history:

  • Progressive supranuclear palsy
  • Bladder stones

    Social history:

  • Disabled by neurologic disorder, previously working as a real estate agent; no tobacco smoking history and no alcohol use

  • Assessment:

    53 year old man with metastatic small blue cell tumor of unknown primary site and an apparent paraneoplastic neurologic syndrome. Based on the pathology report, it is clear that the patient has a small blue cell cancer with neuroendocrine differentation. Without a clear site on the skin that would confirm that this case represents Merkel cell carcinoma, the other competing diagnosis would be small cell lung cancer. A lung lesion was not present at time of initial presentation, but later unilateral "spiculated" lung lesions did appear. There are instances of extensive stage small cell lung cancer in which the primary tumor was clinically occult at presentation.

    It is not possible to definitely sort out whether this case represents Merkel cell carcinoma vs. small cell lung cancer. Given that the vast majority of small cell lung cancer cases are diagnosed among smokers, the lack of significant smoking history in this case lowers the likelihood of lung cancer being the diagnosis.
    But, small cell lung cancer is considerably more common in the overall population than Merkel cell carcinoma.

    The ramifications regarding the residual doubt about the diagnosis will be discussed below and only relates to the issue of whether or not there is a second-line treatment regimen to recommend. The extent of metastatic disease is considerable, with clear involvement of axillary and retroperitoneal lymph nodes, lung, spleen, and bone. The patient has back pain, but no clear evidence of spinal metastases on recent imaging. The patient has received four cycles of carboplatin/etoposide with an apparent mixed response.

    The focus of current treatment considerations regards systemic therapy. Four cycles of carboplatin and etoposide is sufficient to determine who is benefitting from that therapy. I consider a mixed response at that point to be grounds for discontinuing treatment. I reserve additional cycles of the same regimen to those patients who have had clear evidence of a partial response. By far, the greatest experience in the published literature and at major centers currently is with carboplatin/etoposide or cisplatin/etoposide. After that, there is very sparse literature any single approach in the second-line setting. Responses have been reported with single-agent irinotecan, docetaxel, topotecan and liposomal doxorubicin. This list of agents overlaps almost completely with agents that have demonstrated some activity in small cell lung cancer as well. Thus, the remaining uncertainty regarding the underlying diagnosis is, in my view, not particularly relevant when considering the available chemotherapies that one might consider in this patient.

    Certainly, there is no "standard of care" to recommend as second line therapy. So, if the patient is maintaining a good performance status and wishes to pursue subsequent therapy, the single-agents noted above would be considered. I do not know of any ongoing clinical trials (phase II) specifically recruiting patients with metastatic Merkel cell carcinoma. Phase I trials would certainly be a consideration at an academic medical center with access to such trials. The underlying biology of Merkel cell carcinoma is poorly defined and, thus, it is difficult to identify/rcommend a particular type of novel/investigational therapy to consider specifically


    Keith Flaherty, MD