Small cell carcinoma of unknown primary presenting with disease confined to the central nervous system

To the Editor

We refer to an article published recently in your journal [1], in which the authors stated that extrapulmonary small cell carcinoma (EPSCC) “has been recognized at all sites of the body except the central nervous system”. We disagree with this statement and find it ambiguous. If the authors are referring to EPSCC with brain metastases, we argue that this in fact has been widely described [2–9].

Small cell carcinoma of unknown primary (SCUP) is a subset of EPSCC, constituting between 8% [10] to 31% [11] of all EPSCC diagnoses. If the authors are referring to SCUP presenting with central nervous system (CNS) disease, although rare, we have identified one previously reported case in the literature [10]. Furthermore, our institution has recently treated two patients with SCUP who presented with disease isolated to the CNS and who also experienced relapse in the CNS alone.

Both patients were previous smokers, the first a 56-year-old male and the second a 71-year-old female. Both initially presented with a solitary intracranial lesion that was resected. Histology was consistent with small cell carcinoma, and no other sites of disease were found on staging investigations (computed tomography of the chest, abdomen and pelvis and whole body bone scan). Both patients received whole brain radiotherapy (30 Gy in 10 fractions). After 16 and 21 months respectively, both patients relapsed with isolated spinal intradural extramedullary disease that was surgically debulked. Histology was again consistent with small cell carcinoma. Both patients received radiotherapy to the involved spine (30 Gy in 10 fractions), followed by carboplatin (AUC 5, Day 1) and etoposide (120mg/m² Days 1–3) chemotherapy. The first patient completed four cycles and remains alive and well 33 months after the initial diagnosis. The second patient developed pneumonia and an acute myocardial infarction after cycle 1, and died shortly thereafter (24 months after the initial diagnosis). In a recent retrospective study, median survival for SCUP was only 2.5 months [11]. By comparison, our patients experienced prolonged disease-free and overall survival.

In summary, not only does EPSCC metastasise to the brain, but SCUP can also present initially in the CNS as demonstrated by the two cases we have described.