Mimicker of acute leukaemia
Dr.Edmond S.K.Ma

Division of Haematology, Department of Pathology,
The University of Hong Kong, Queen Mary Hospital, Hong Kong

Case Presentation:

An 80-year old Chinese gentleman with previous history of diabetes mellitus and ischaemic heart disease was admitted into hospital for markedly deteriorated general condition, cough, shortness of breath and abdominal distension. Physical examination showed a moribund patient. The liver was grossly enlarged. There was also pallor and diffuse coarse crepitations over his right lung.

A chest radiograph (Figure 1) showed right paratracheal and hilar mass suspicious of an endobronchial lesion with secondary obstruction or consolidation. The right minor fissure was thickened. Ultrasonogram showed diffuse infiltrative lesion of the liver parenchyma.

Blood counts showed: haemoglobin 7.1 g/dL, white cells 7.3 X 10⁹/L (leucoerythroblastic picture), and platelets 48 X 10⁹/L. His clotting profile was normal without evidence of disseminated intravascular coagulation.

A bone marrow aspiration and trephine biopsy was undertaken to investigate the anaemia and thrombocytopenia. The marrow was hypercellular and being heavily infiltrated by blast cells (Figure 2) with cell sizes ranging from small to medium to occasionally large (Figure 3). They showed high nuclear cytoplasmic ratio, somewhat speckled to fenestrated chromatin (Figure 2) and scanty cytoplasm. They were not particularly cohesive in appearance. Normal haemopoietic elements were severely depressed. An initial morphological diagnosis of acute leukaemia was made. Blast cells were cytochemically inert. A panel of myeloid and lymphoid markers including LCA (CD45) was negative, thus throwing the diagnosis of acute leukaemia in doubt. The infiltrate cells may be non-haemic in origin, but nevertheless, rare forms of acute leukaemia (such as undifferentiated, erythroblastic or megakaryoblastic leukaemia) were not entirely excluded.

The trephine biopsy was more revealing. The marrow architecture was distorted and showed infiltration by cohesive clusters of tumour cells associated with a desmoplastic reaction (Figure 4). The tumour cells were predominately small in size showing fine chromatin, frequent mitosis and nuclear dust (Figure 5). Normal haemopoiesis was virtually absent. Immunohistochemical staining showed that tumour cells were negative for LCA, cytokeratin and synaptophysin. They were uniformly positive for CD56 and isolated cells were positive for chromogranin. A diagnosis of metastatic small round cell tumour was made.

The patient ran a rapid downhill course and succumbed to the malignancy. A paramortem liver biopsy showed infiltration of liver sinusoids by small round cell tumour together with several confluent areas of tumour infiltration.

Diagnosis:

Metastatic small round cell tumour to bone marrow and liver, most probably from a primary site in the lung.

Discussion:

Metastatic involvement of the bone marrow by malignant small round cell tumour is not uncommonly encountered in paediatric patients, and these tumours include neuroblastoma, Ewing's sarcoma and rhabdomyosarcoma. In some patients, bone marrow disease may be the primary manifestation, thus mimicking acute lymphoblastic leukaemia that is a commoner malignancy in the paediatric age group.

However, as illustrated by the present case, metastatic small round cell tumour (for instance oat cell carcinoma of lung as in our patient) may be confused with acute leukaemia even in the adult population. We should therefore be vigilant for this albeit rare possibility especially in atypical cases. The following points may assist in the correct diagnosis of malignant small round cell tumours and distinguishing them from acute leukaemia:

1. A leucoerythroblastic picture but without obvious circulating leukaemic blasts.
2. Tumour cells commonly show speckled to fenestrated (small holes) chromatin in contrast to the fine and open chromatin seen in acute leukaemia. They tend to be cohesive. Special morphological features include rosette formation and fibrillary background in neuroblastoma and cytoplasmic vacuolation in rhabdomyosarcoma.
3. Immunohistochemical study is mandatory. CD56, which was uniformly expressed by the tumour cells in our case, was a highly sensitive marker for diagnosis of small cell carcinoma both of pulmonary and extrapulmonary origin (Kaufmann et al, Hum Pathol 28:1373-8, 1997). The positivity for chromogranin in our case was also in keeping with the putative neuroendocrine nature of this tumour.
4. Finally, correlation with clinical and radiological features is helpful which may point towards the diagnosis of metastatic disease over acute leukaemia.

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