Metastatic malignant melanoma intraoperative imprint cytology of brain tumor.

Metastatic neoplasm to the brain is not a rare event and approximately 10% of patients with cancer develop brain involvement. Although brain metastases usually appear late in the course of the disease, it may be an initial symptom of the primary tumor. Small-cell lung cancer, HER-2-positive breast carcinoma, renal cell carcinoma, malignant melanoma and colorectal adenocarcinoma are the most common primary sites. The distinction between a primary brain tumor and a metastatic neoplasm is important because surgical and therapeutic treatments vary accordingly.[1-3] In this report, the role of intraoperative imprint cytology as an important diagnostic modality in the diagnosis of brain tumor is described in two cases.

A 54-year-old woman was admitted in neurosurgery department with generalized headache and episodes of syncope. She was a known case of cutaneous malignant melanoma since 3 years. In computed tomography and magnetic resonance imaging (MRI) a mass with ringed enhancement in the left parietal lobe was noticed. Multiple hyposignal areas on T2 sequence were noted within the mass, probably representing melanin component or calcification. The patient underwent tumor excision. The intraoperative smears were highly cellular composed of discohesive sheet of medium sized epithelioid cells with prominent eccentric nucleoli, intranuclear inclusions of cytoplasm, punched-out intranuclear vacuoles and dense abundant cytoplasm [Figure 1]. Few multinucleated tumor cells and mitotic figure were also present. Intracytoplasmic melanin pigment could be identified easily.

Figure 1

Discohesive sheet of malignant cells with eosinophilic cytoplasm, multiple punched-out nucleoli and abundant melanin pigments (H and E, ×400)

The second case was a 60-year-old man, known case of melanoma, referred to neurosurgery services with headache and vomiting. In imaging study, the tumor was localized to the frontal lobe. The intraoperative smear was composed of polygonal and oval-shaped malignant cells in necrotic background. Coarsely granular and clumped brown-black melanin pigment could also be identified both in the cytoplasm of tumor cells or lying free in the background. Immunohistochemistry on permanent formalin-fixed paraffin embedded tissue for S-100, HMB-45 and Melan-A were positive in both cases.

Radiographically, distinction between a primary high-grade brain tumor and a metastatic deposit is difficult in ring enhancement lesions.[4]

In imprint cytology of brain tumor, high-grade glioma, glioblastoma, germinoma and primary central nervous system lymphoma (PCNSL) should be considered in differential diagnosis of metastatic lesions.[356]

Carcinomas are the most common form of metastases in the central nervous system. In metastatic non-small cell carcinoma, discohesive sheet as well as isolated malignant cells with overlapping nuclei, prominent nucleoli and necrotic background is easily seen.[45]

The cells tend to stick together in small group. Acinar pattern and intracellular vacuoles can be seen in mucin-secreting adenocarcinoma.

In metastatic small cell carcinoma and oat cell carcinoma, the cells have little cytoplasm with high nuclear/cytoplasmic ratio. Nuclear chromatin is evenly dispersed and nucleolus is not prominent. The cells have tendency to form small clusters; this is useful in differentiating them from lymphoid cells. However, given a history of previous cancer is very important.

Anaplastic astrocytoma is cellular and shows variable degree of undifferentiated cells which may no longer be recognized as astrocyte. Nuclei are pleomorphic and bizarre with multinucleate forms often seen. Mitotic figures with vascular proliferation are present. Some tumor cells have tendency to remain attached to blood vessels in anaplastic astrocytoma, a helpful feature in differentiating it from metastatic carcinoma.

Glioblastomas contain mitotic figures, some of which may be abnormal with areas of necrosis. The tumor cells range from small cells, representing small cells GBM to large pleomorphic cells with prominent nucleoli, the giant cell variant. The tumors may be undifferentiated and contain multinucleate and bizarre cells with little or no glial differentiation. A small percentage of glioblastoma are composed of cells with an epithelioid appearance with discrete cell borders and pseudo-gland arrangement.

The germinoma usually occurs in the first two decades of life, with predilection for the midline. The smears are composed of mixture of large cells with vesicular nuclei and prominent nucleoli, and lymphocytes.

The cells in oligodendroglioma typically have scant, process-poor cytoplasm with uniform round nuclei.[4-6]

In PCNSL; the smears display mixture of small and large cells with scant cytoplasm in well-defined borders. The cells contain large nuclei with coarse chromatin and prominent nucleoli. Apoptosis is common. The cells lack cohesiveness and nuclear molding of metastatic carcinoma, and fine processes of glial neoplasms.

Melanoma is composed of cells with plentiful cytoplasm, eccentric nuclei, prominent macronucleoli and melanin pigment. It should be considered that melanin may also be present in other CNS tumors such as ependymoma, meningioma and schwannoma. Despite anaplasia, melanoma nuclear membranes tend to be less irregular and convoluted and the cells have good amount of cytoplasm, a helpful findings in differentiating it from PCNSL.[56]

In difficult cases, frozen section should be performed to demonstrate relative demarcation from surrounding brain tissue, to exclude the epithelioid glioblastoma and amelanotic melanoma.

Although, knowledge of patient's prior history was helpful for diagnosis; however, the possibility of second malignancy especially in old age should be considered.[356]

We feel that imprint cytology is a useful and rapid method for making diagnosis during operative consultation and assist the neurosurgeon to take management decision.