Sclerosing Paraganglioma: An Unusual Variant with Diagnostic Pitfall of Malignancy

Paragangliomas (PGs) are non-epithelial tumors arising from neural crest derived paraganglionic cells. Approximately 57 % of PGs in the head and neck are originated from carotid body. The tumors are generally non-functioning and often diagnosed due to cervical nerve compression effect. Typically, PGs show the characteristic organoid pattern surrounded by sustentacular cells and embedded in a vascular rich stroma. Unusual morphological features, such as prominent stromal sclerosis (sclerosing PG) may be seen in some cases, which may raise concerns of malignancy. The differential diagnosis of sclerosing PG in the head and neck area can be wide. The presence of cytological atypia with infiltrative morphology in a sclerotic stroma may mimic desmoplastic reaction of a metastatic carcinoma. Presence of the sustentacular cells and zellballen pattern with absence of significant mitotic activity and necrosis in sclerosing PG can be helpful to distinguish it from malignancy. Negative immunoreactivity of tumor cells in PGs for epithelial markers (e.g. cytokeratins and EMA) is also valuable in comparing with diffuse positivity in metastatic carcinomas.CASE PRESENTATION: A 55 year-old woman presented with flushing, headache, sweating, weight loss and a painless lump on zone II of the neck. A magnetic resonance imaging (MRI) scan demonstrated a hypervascular lesion originating from the carotid body with adherence to the carotid artery. During surgical excision, adhesion of the tumor to the surrounding structures caused concern for the surgeon and intraoperative consultation was requested. Part of the lesion had been sent to the pathology lab and due to sclerotic nature of the lesion, final diagnosis was deferred to permanent sections. Subsequent gross evaluation of the excisional specimen showed an ill-defined, whitish nodule, measuring 4.5 cm in the greatest dimension. Microscopically, the most striking feature was the presence of an abundant sclerotic stroma separating irregular nests, islands, or cords of tumor cells. Conspicuous nuclear pleomorphism and enlargement associated with perineural invasion was also evident. Mitoses were sparse (<1 x 10 HPF). Neoplastic cells were immunoreactive for chromogranin and synaptophysin whereas cytokeratin AE1/AE3 was negative. S100 highlights a sustentacular cells network. No immunoreactivity for calcitonin is identified.CONCLUSION: Although, a sclerosing variant of PG is a rare subtype but it could be very challenging, especially during intraoperative consultation. Morphological features could be a potential pitfall and may lead to over-diagnosis of malignancy. Therefore, awareness of this extraordinary growth pattern of PG and proper immunostains allows the pathologist to reach the correct diagnosis.

Keywords:

Paraganglioma , Sclerosing paraganglioma , Carotid body tumor