Fine needle aspiration diagnosis of extracranial glioblastoma multiforme: Case report and review of the literature

Background

Extracranial metastasis of primary brain malignancies is an uncommon event [1]. With increased patient survival due to new treatment options, however, the incidence of extracranial metastases of brain malignancies may increase, as has been the case with systemic cancers. An alternative to tissue biopsy to determine whether or not extracranial spread has occurred, is fine needle aspiration (FNA) biopsy. An FNA biopsy has several advantages over tissue biopsy, including immediate evaluation of tissue adequacy, minimal risk to the patient and the possibility of multiple passes to reduce the risk of sampling error. Because of the rarity of metastases of primary brain malignancies, the cytological findings of metastatic primary brain tumors are limited to only a few accounts. A literature review produced a total of five articles pertaining to the FNA biopsy features of extracranial metastatic primary brain tumors [2-6]. Four of the articles involved gliomas (three glioblastoma multiforme [3,4,6], and one low-grade astrocytoma [5]) and one pertained to a sacrococcygeal myxopapillary ependymoma [2]. This case report is submitted to detail the cytological findings in an extracranial glioblastoma multiforme (GBM).

Case presentation

Microscopic description

The smears were abundantly cellular with atypical cells arranged in loosely cohesive clusters, ranging from 5 to 40 cells per cluster, with overlapping nuclei (Fig. 1A–1D). Scattered atypical mitoses were also present (Fig. 1C). Morphologically, the cells were polygonal to spindle-shaped with increased nuclear to cytoplasmic ratios, moderate nuclear pleomorphism, coarsely clumped hyperchromatic chromatin, irregular nuclear membranes, and distinct nucleoli. Binucleated and multinucleated cells were also noted. A few scattered intranuclear inclusions were present (Fig. 1D). Fibrillary processes extending from the atypical cells were apparent. A tumor diathesis consisting of neutrophils, degenerated cells, necrotic debris, a few lymphocytes, and bare nuclei made up the background. The cell block showed similar findings as well as characteristic necrotic foci surrounded by palisading spindle-shaped atypical cells (geographic necrosis) (Fig. 2A). Immunohistochemically, the atypical cells displayed strong reactivity for GFAP (Fig. 2B) and vimentin with no reactivity for CD45, cytokeratin, and HMB-45, supporting the diagnosis of GBM. The histological sections from the tumor excised a month later verified the FNA findings of GBM (Fig. 2C–2D).

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Figure 1

Figure 1A: Smear showing abundant cellularity and necrosis (Diff-Quik ® stain, X100). Figure 1B: Smear showing atypical cells in loosely cohesive clusters (Diff Quik ® stain, X400). Figures 1C and 1D: Smears showing pleomorphic cells with coarsely clumped chromatin, irregular nuclear membranes, prominent nucleoli, atypical mitosis (1C, arrow), intranuclear inclusion (1D, arrow) and cellular processes (Papanicolaou stain X400)

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Figure 2

Figure 2A: Cell block showing geographic necrosis (H&E stain, X400). Figure 2B: Cell block showing positive staining of malignant cells for glial fibrillary acidic protein (immunostain for GFAP, X400). Figure 2C: Histology of surgical resection showing malignant cells with numerous mitotic figures in a desmoplastic background (H&E stain, X400). Figure 2D: Histology of surgical resection showing positive staining of malignant cells for glial fibrillary acidic protein (immunostain for GFAP, X400).

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Conclusion

The cytologic and immunohistochemical features of this FNA, augmented by the patient's history of GBM, led to a straightforward diagnosis in this case. In the absence of a detailed clinical history, however, a consideration of other malignant neoplasms that occur in the scalp may be necessary in the initial work up. Table 1 gives a brief differential comparing the cytological features of other malignancies that may occur in the scalp of adults.

Extracranial spread of GBM, although rare, is a recognized phenomenon with an estimated incidence of less than 0.5%. It usually occurs in patients with a history of a previous craniotomy or a diversionary shunt. Proposed routes of dissemination include implantation of tumor during open surgery and during stereotactic biopsy [8]. Rare cases of spontaneous metastasis without a history of biopsy or surgery have been reported in the literature [9]. The first well-documented extracranial metastasis was reported in 1928 [10]. The sites of metastasis vary with the type of brain primary and include bone, lung, liver, and lymph node. In the pediatric population, medulloblastoma is the leading tumor for extracranial metastasis. In the adult, it is malignant astrocytoma/GBM. True metastases as well as extracranial recurrences have been reported as being diagnosed by FNA biopsy [7].

In previous reports, as well as this one, the specimens procured by FNA from extracranial GBM are quite cellular consisting of malignant-appearing cells arranged in small, loosely cohesive, disorderly clusters with a predominance of single cells. Cellular size ranges from small to large with variably shaped nuclei ranging from round to oval to spindle. All descriptions consistently include marked nuclear pleomorphism with high nuclear to cytoplasmic ratios, coarsely clumped hyperchromatic chromatin, nuclear membrane irregularity, prominent single or multiple nucleoli, multinucleation and necrosis. Occasional intranuclear and cytoplasmic inclusions and rare mitoses may be seen. Scant cytoplasm is noted in all cases; however, the presence of cytoplasmic processes extending from the malignant cells creating a fibrillary background (a characteristic feature for astrocytic neoplasms) is not described in all cases. A GFAP stain may be helpful in highlighting this feature. Thick-walled capillaries with endothelial proliferation are documented in one case study [4], but this feature is absent in our case, even with immunostaining for CD34. Cell block sections do reveal the characteristic geographic necrosis typical of GBM. In addition, the cell block allows the performance of a panel of immunostains. For this reason we recommend submitting at least one FNA pass, solely for the purpose of obtaining a cell block. As in this case, the cell block may be extremely helpful in rendering a definitive FNA diagnosis of this rare extracranial tumour.