Small Round Blue Cell Tumours

A microscopic specimen of a tumour may show a small round blue cell tumour. These tumours are characterised by the presence of cells that are:

  • Small (similar to lymphocyte in size)
  • Round (round cells)
  • Blue (blue staining due to high nuclear/cytoplasmic ratios

It can be a challenge to determine the exact origin of these tumours. The typical small round blue cell tumours in humans are:

  • Poorly differentiated neuroendocrine tumours (e.g. small cell lung cancer, Merkel cell carcinoma)
  • Indolent B cell lymphoma (chronic lymphocytic leukaemia, follicular lymphoma with no centroblasts)
  • Melanoma (some variants)
  • Paediatric age tumours
    • Ewing sarcoma
    • Alveolar rhabdomyosarcoma
    • Nephroblastoma
    • Medulloblastoma
    • Desmoplastic small round cell tumour (often in the peritoneum)
  • Olfactory neuroblastoma

The likelihood of each diagnosis depends on the site and age of the patient as well as, in some cases, risk factors.

Type Site Age Risk Factors Architecture Immunohistochemistry
Small Cell Lung Cancer Lung Mean age 50-60 Smoking Neuroendocrine TTF1+, CK7+, CK20-,
Synatophysin +,
Chromogranin +
Merkel Cell Carcinoma Skin Mean age 60-70 Sun exposure Nests, sheets TTF-, CK20+,
Synaptophysin +,
Chromogranin +
Lymphoma Nodes Mean age 50-60 None Variable; follicular CD79a+, CD20+
Ewing Sarcoma Bone Mean age 10 None Sheets, occasional rosettes CD99+, vimentin
Alveolar Rhabdomyosarcoma Extremities, other sites Mean age 10-20 None Nests, fibrovascular stroma Myo-D1 +ve
Nephroblastoma Kidney Mean age 3-4 WAGR, Beckwith-Weidermann
Triphasic (blastemal,
epithelial, stromal)
Vimentin +, WT1 +
Desmoplastic SRCT Peritoneum Unknown Large nests,
Desmoplastic stroma
Cytokeratin, NSE +


The age and site of the tumour may provide sufficient diagnostic information in most cases; for instance, in a 65 year old smoke with a lung mass with biopsy showing small round blue cells, the likelihood of small cell carcinoma of the lung is incredibly high. An important differential is in children with a bony lesion, where it may be due to a primary Ewing sarcoma or alternatively a metastasis from nephroblastoma, rhabdomyosarcoma or other embryonal tumour. Immunohistochemistry is especially helpful at differentiating the neuroendocrine tumours from the embryonal tumours, and the embryonal tumours from each other.