A 37-year old Chinese man who worked as a missionary complained of right hip pain and low back pain associated with a left popliteal mass for half a year. Since one month prior to admission, he complained of low-grade fever and chills, subjective weight loss and poor appetite. He also developed haemoptysis for a couple of times.

Physical examination showed enlarged lymph nodes over the left groin and medial aspect of left thigh. The left popliteal mass is likely to be enlarged lymph nodes matted together. There was a 0.5 cm pigmented lesion over the left sole.

The chest radiograph showed haziness over the right upper zone and left lower zone. Skeletal survey showed wedge collapse of T12 and L1 spine vertebral bodies and an osteolytic lesion over the inferolateral quadrant of the right femoral head. Bone-scan showed uptake at right ilium consistent with malignancy.

Complete blood counts showed: haemoglobin 10.5 g/dL, white blood cells 8.3 X 10⁹/L, and platelets 42 X 10⁹/L. Peripheral blood film revealed a leucoerythroblastic blood picture (Figure 1).

Figure 1: Leucoerythroblastic blood film

Bone marrow aspiration yielded no particles but trails were cellular. The bone marrow is infiltrated by large abnormal cells having round to mildly irregular nucleus, coarse chromatin texture, one to two small nucleoli and appreciable amount of cytoplasm that was sometimes vacuolated (Figure 2). They were mostly scattered in distribution although a few small cohesive clusters were present.

Figure 2: Tumor cell infiltrating the bone marrow

On close inspection, a sizable proportion of the abnormal cells showed brownish cytoplasmic pigmentation (Figure 3 and 4). Some of the background histiocytes also contained cytoplasmic pigment (Figure 5).

Figure 3: Tumor cells with and without cytoplasmic pigment.	Figure 4: Tumour cells with dusty and brownish cytoplasmic pigments
Figure 5: A histiocyte with cytoplasmic pigment together with 2 neutrophils in this field

Trephine biopsy showed hypercellular marrow with heavy infiltration by malignant cells in a diffuse manner and corresponding coarsening of reticulin fibres. The tumour cells were pleomorphic and loosely cohesive. They showed hyperchromatic nucleus and distinct nucleolus. Cytoplasmic pigments were seen in some tumour cells (Figure 6) and histiocytes (Figure 7). Focal areas showed bone marrow necrosis (Figure 8). Normal haemopoiesis was markedly depressed.

Figure 6: Heavy bone marrow infiltration by tumour cells as shown in trephine biopsy sample	Figure 7: Trephine biopsy showing pigments in histiocytes
Figure 8: Bone marrow necrosis and associated osteonecrosis. Please note tumour cells appearing as eosinophilic cell ghosts and empty lacunae in bony trabeculae with loss of osteocytes.

Immunohistochemical staining on trephine biopsy showed that the tumour cells were negative for leucocyte common antigen (LCA) and cytokeratin. They are positive for S-100 protein (Figure 9) and HMB-45 (Figure 10).

Figure 9: Positive immunostaining for S-100 protein

Figure 10: Positive immunostaining for HBM-45

Diagnosis

Malignant melanoma infiltration of the bone marrow

Clinical course

A clinical diagnosis of malignant melanoma with lymph node, bone marrow, osseous and probable lung metastasis was made. The patient volunteered a history of excision of left plantar lesion (Figure 11) 18 months ago while working in Korea, but the specimen was not sent for pathological examination.

The primary lesion was not re-biopsied. The poor prognosis and short survival was explained, and the patient received palliative radiotherapy to right hip and pelvis for pain control.

Figure 11: The primary lesion

Discussion

Malignant melanoma is present in the bone marrow is approximately 5% of patients with disseminated disease. If melanin is found in the tumour cells or macrophages as brown pigments, the diagnosis is relatively straightforward.

Not infrequently, however, metastatic melanoma is amelanotic. Moreover, as in the present case, the clinical history may not be initially forthcoming and the lesion may be hidden or not obviously pigmented. In these cases, metastatic melanoma should be suspected if the tumour comprised histologically polygonal or spindle cells with prominent nucleoli. Immunohistochemical study is useful in supporting a diagnosis of malignant melanoma. They are almost always negative for LCA and cytokeratin. More than 90% of malignant melanoma express S-100 protein. HBM-45 is less sensitive (expressed in 50% of cases) but more specific than S-100 protein. Our case is in fact entirely typical of malignant melanoma based on morphology and immunohistochemistry.