Metastatic spindle cell melanoma on cytology – a diagnostic challenge

Spindle cell melanoma is a rare variant of malignant melanoma and the diagnosis on fine needle aspiration cytology (FNAC) can be extremely difficult [1,2]. An accurate cytological diagnosis is important owing to the prognostic and therapeutic implications. It also directs staging, treatment and prognosis. The incidence of spindle cell melanoma varies from 3%14%. Spindle cell melanoma can occur anywhere on the body. Typically, it often presents with widespread metastatic disease [2,3]. However some melanomas may present as a metastasis of unknown primary origin while others may take several decades to develop metastasis [4].


INTRODUCTION
Spindle cell melanoma is a rare variant of malignant melanoma and the diagnosis on fine needle aspiration cytology (FNAC) can be extremely difficult [1,2].An accurate cytological diagnosis is important owing to the prognostic and therapeutic implications.It also directs staging, treatment and prognosis.The incidence of spindle cell melanoma varies from 3%-14%.Spindle cell melanoma can occur anywhere on the body.Typically, it often presents with widespread metastatic disease [2,3].However some melanomas may present as a metastasis of unknown primary origin while others may take several decades to develop metastasis [4].

CASE REPORT
A 61 year old male came with a history of a mole over the right foot since 4 months.It was insidious in onset and rapidly progressive in size.He had also noticed a swelling in the right thigh.There was no history of fever or chills, loss of weight or appetite.On examination there was a greyish plaque present over the right foot and right inguinal lymphadenopathy.Ultrasonography of the abdomen revealed few enlarged right external iliac lymphnodes and right inguinal lymphnodes.FNAC of the inguinal node was done, followed by wide local excision of the lesion over the right foot followed by right inguinal block dissection.
FNA smears showed clusters & fascicles of spindle cells with slender elongated nuclei and scant cytoplasm, in a background of macrophages, lymphocytes few neutrophils and necrosis.The nuclei displayed a bland morphology.Occasional cells showed mild pleomophism.Macronucleoli and melanin pigment were absent (Fig. 1 and 2).A diagnosis of spindle cell lesion was rendered and in view of the history, a possibility of metastatic spindle cell melanoma was suggested.Grossly, the wide local excision biopsy specimen showed a surface ulcer measuring 2.5 x 2 cm and the cut section showing grey brown areas.18 lymphnodes were isolated from the right inguinal block dissection specimen.A diagnosis of spindle cell variant of malignant melanoma (Clarks level IV) with lymph node metastasis was finally rendered (Figs. 3  and 4).Radiation oncology consultation was sought and the patient was advised computerized tomography of thorax, abdomen and pelvis.

DISCUSSION
Cytological features of spindle cell melanoma include predominantly dyscohesive spindle cell cluster, interlacing fascicles and whorls of slender spindle cells with illdefined cell borders, variable amount of cytoplasm, often showing bipolar long cytoplasmic projections which may have curved or twisted ends [5][6][7].The presence of epitheloid cells has also been noted, few of which display classical cytological features of conventional melanoma.Cytoplasmic melanin pigments are variably observed [2,7].The nuclei of the spindle cells vary from oval to slender, with occasionally folded nuclear membrane.Intranuclear pseudoinclusions are also variably noted.The chromatin is usually granular and delicate, nucleolus being inconspicuous and occasionally prominent [6,8].
The spindle cells can also show varying degrees of cytological atypia, ranging from pleomorphic cells seen in high grade sarcomas to deceptively bland cells which resemble reactive fibroblasts [9,10].The classic cytologic features of conventional melanoma which include predominantly dyscohesive clusters of cells, melanin pigments, intranuclear pseudoinclusions, eosinophilic macronucleoli, and binucleation or multinucleation are not frequently noted in spindle cell melanomas making the diagnosis more challenging and difficult (Table 1).
There are two distinct subtypes of malignant melanoma that differ clinic-pathologically and with respect to prognostic features.These include the spindle cell variant and desmoplastic melanoma [2,3,11].Both these tumors show atypical, spindle malignant    melanocytes.In desmoplastic melanoma, these malignant cells are intimately admixed with ropy and dense collagen fibrils which was absent in the present case.
Other spindle cell lesions that fall into the differential diagnosis include atypical fibroxanthoma, cutaneous leiomyosarcoma, dermatofibrosarcoma protruberans, synovial sarcoma and spindle cell squamous cell carcinoma.However the clinical features of each of these entities differ and must be correlated with cytology findings (Table 2).
The immunohistochemical markers used to confirm a melanocytic nature include S-100, HMB-45, Melan-A, and MART-1, the latter 3 being relatively specific but less sensitive markers for melanomas.Loss of expression of these makers has also been noted in spindle cell melanomas and few of them aberrantly express cytokeratin(10%) and smooth muscle actin [2,3,8].In the present case HMB-45 was positive in the tumor cells.

CONCLUSION
Spindle cell melanoma may often be confused with other spindle cell lesions due to the lack of the characteristic features of conventional melanoma.A good clinical history is often helpful.FNAC is often used to document recurrent or metastatic disease and thus plays a very important role.Additional sources of diagnostic challenges, especially in the metastatic setting include varying degrees of cytologic atypia and possible cell type differences from the primary counterpart.

ACKNOWLEDGEMENT
We would kindly like to thank all the technical staff of the department of histopathology.

CONSENT
The examination of the patient was conducted according to the Declaration of Helsinki principles.

Table 1 :
Cytological fi ndings of metastatic spindle cell melanoma compared with that of conventional melanoma Cytological

Table 2 :
Differential diagnosis of spindle cell lesions Spindle cells arranged in bundles, nuclei are round to oval, vesicular, moderate amount of tapering cytoplasm.Mitotic fi gures may be abundant and may also single cells with pleomorphic nuclei Synovial sarcoma Young patients Around joints Short, uniform spindle or epithelial cells with uniform vesicular nuclei and micronucleoli.Gland formation in biphasic lesions is a useful diagnostic feature.Plump spindle shaped cells with vesicular nucleus, arranged in fascicles, large polyhedral cells, few being vacuolated; bizarre giant cells (mononucleate or multinucleate) with hyperchromatic nuclei.