Gliosarcoma with PNET features mimicking a metastatic neuroendocrine carcinoma: A diagnostic dilemma.

OBJECTIVE: Gliosarcomas (GS) comprise ~ 2 - 8% of glioblastomas and are associated with a similar poor prognosis. GS have rarely been found with a primitive neuroectodermal component (PNET). We present a case of gliosarcoma with PNET features (GS-PNET) that mimicked a neuroendocrine carcinoma on initial biopsy. MATERIALS AND METHODS: A 68-year-old male presented with 2 weeks of increasing headaches and difficulties with reading, writing, and word-finding. He was found to have a left-sided parieto-occipital heterogeneously enhancing mass. RESULTS: Pathologic analysis after surgical resection initially diagnosed a poorly differentiated carcinoma with neuroendocrine features, and adjuvant therapy was guided by this diagnosis as well as systemic imaging, which was suggestive of gastrointestinal primary malignancy with central nervous system (CNS) metastasis. Subsequent progression and re-resection established a diagnosis of GS with PNET component. Genomic profiling showed shared PTEN, TERT promotor, and TP53 mutations in the original and recurrent tumors. CONCLUSION: There have only been 5 previously reported cases of GS-PNET, to our knowledge, with this case representing the first with comprehensive molecular profiling. The case also highlights the importance of further work-up of presumed metastatic carcinoma with indeterminate immunostaining and/or suspected non-epithelioid component.

Craniospinal irradiation for respiratory failure secondary to central nervous system Erdheim-Chester disease.

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis typically featuring lower extremity osteosclerosis (96%) from Langerin-negative histiocytes with fibrosis. Central nervous system (CNS)-only disease is extremely rare, and particularly difficult to diagnose and manage. Neurologic complaints may be refractory to systemic therapy (ST), and the role of radiation therapy (RT) is undefined. We present a patient with ECD of the medulla complicated by respiratory failure and strength deficits with disseminated leptomeningeal disease (LMD) but not systemic disease, representing the first report of CNS-limited ECD with LMD. He received upfront craniospinal irradiation (CSI), representing a rare account of CSI for ESD, with marked clinical improvement resulting in extubation and improved strength. CSI facilitated excellent preservation of quality of life, and no treatment-related toxicity was observed prior to eventual, unrelated cardiopulmonary arrest. Thus, palliative CSI may augment ST by safely offering improved local control and symptomatic relief for CNS ECD.

Neuropathology of Pituitary Adenomas and Sellar Lesions.

The pituitary gland is the site of numerous neoplastic and inflammatory processes. The overwhelmingly most frequent tumors arise from cells of the anterior lobe, the pituitary neuroendocrine tumors (PitNETs). Immunohistochemistry assay staining for pituitary hormones is the core tool for classifying PitNETs, resulting in the diagnosis of somatotroph PitNETs, lactotroph PitNETs, and so on. For cases showing no hormonal expression, the updated WHO classification system now considers the assessment of several transcription factors: PIT-1 (pituitary-specific POU-class homeodomain transcription factor); T-PIT (T-box family member TBX19); and SF-1 (steroidogenic factor regulating gonadotroph cell differentiation) before rendering a diagnosis of null cell adenoma. Other tumors and disease processes of this site often mimic PitNETs radiographically and sometimes even clinically (ie, compression of the optic chiasm). These potpourri of processes include germ cell neoplasms (especially germinomas), tumors that originate from Rathke's pouch (craniopharyngiomas, Rathke's cleft cyst), tumors that originate from the posterior lobe of the pituitary (pituicytoma, spindle cell oncocytoma, granular cell tumor), and tumors that originate from the meninges (especially meningiomas). In addition to neoplasms, several described inflammatory and related conditions exist that need to be distinguished from PitNETs. These include lymphocytic hypophysitis and Langerhans cell histiocytosis, a neoplastic disorder of histiocytes. In this review, we aim to briefly describe the main pituitary and sellar lesions, with emphasis on the most common tumors, the PitNETs.

p16INK4A expression is frequently increased in periorbital and ocular squamous lesions.

BACKGROUND: p16 expression is a well established biomarker of cervical dysplasia and carcinoma arising from high risk human papilloma virus infection. Increased p16 expression is also seen in squamous neoplasms arising at other sites, including head, neck, and oropharyngeal tract. Squamous lesions are also frequently encountered at ocular surface and peri-orbital skin sites, but the prevalence of increased p16 expression in these lesions has been poorly studied. METHODS: We retrospectively surveyed 13 ocular surface and 16 orbital squamous lesions biopsied at UC San Diego Healthcare System and VA San Diego Healthcare System for p16 expression by immunohistochemistry. These cases included ocular surface lesions with diagnoses of conjunctival intraepithelial neoplasm (CIN) and squamous cell carcinoma in situ. Peri-orbital eyelid biopsies included lesions with diagnoses of SCCis and invasive squamous cell carcinoma. We performed multivariate logistic regression, followed by student's T-test or Fisher's exact test to determine if there were statistically significant associations between p16 immunoreactivity and patient age, gender, diagnosis, and ethnicity. Statistical significance was defined as p < 0.05. RESULTS: We found an unexpectedly large prevalence of strong nuclear and cytoplasmic p16 immunoreactivity in our cases. Almost all of the ocular surface squamous lesions were diffusely positive for p16 expression (12/13). All of the periorbital lesions showed diffuse p16 immunoreactivity (16/16). Altogether, 28/29 lesions tested showed strong and diffuse p16 expression. We found no statistically significant correlation between p16 expression and patient age, gender, ethnicity, or diagnosis. In 6 of the peri-orbital biopsies, we had sufficient tissue to assess high-risk HPV expression by in situ hybridization. Interestingly, all of these cases were negative for HPV, despite strong p16 expression. CONCLUSION: Strong p16 expression was observed in virtually all of the ocular surface and peri-orbital squamous neoplasms in our study. The relationship between p16 expression and HPV infection in ocular surface and peri-orbital sites requires further investigation.