Characterization of spinal hemangioblastomas in patients with and without von Hippel-Lindau, and YAP expression.

INTRODUCTION: Hemangioblastoma (HB) is a benign tumor of the central nervous system, associated with von Hippel-Lindau disease (VHL), or sporadic. The aim of this study was to compare and examine the clinical-pathological profile of patients with spinal hemangioblastoma and YAP expression. METHODS: A retrospective, descriptive, comparative study. All patients who underwent surgery for spinal HB between 2016 and 2023 were included. Clinical and radiological data were collected and analyzed. An immunohistochemistry panel including NeuN, neurofilaments (NF), and YAP-1, was performed. RESULTS: Nine patients were studied, six women and three men. Four patients had previously diagnosed VHL. The tumor location included: four cervical (44.44%), two thoracic (22.22%), two pontine with cervical extension (22.22%) and one patient with two lesions, one cervical and one thoracic (11.11%). Non-significant clinical differences were identified between VHL and sporadic patients. Imaging evidenced seven extramedullary and three intramedullary tumors. Histologically, intra-tumoral and perivascular axonal tracts were observed in all cases. One third of the tumors (two with VHL and one sporadic) presented extramedullary hematopoiesis. Seven cases (77.8%) expressed nuclear YAP (three with VHL and four sporadic HBs). The surgical outcome was good and only one patient with VHL undergoing subtotal resection had recurrence. CONCLUSIONS: Spinal HBs can be associated with VHL or be sporadic. To the best of our knowledge, this is the first study to describe YAP expression in HB. It is important to investigate the involvement of the Hippo pathway in HBs as a possible therapeutic target.

Solitary fibrous tumour/haemangiopericytoma of the spinal cord. / Tumor fibroso solitario/hemangiopericitoma de la médula espinal.

Solitary fibrous tumours/haemangiopericytomas (SFT/HPC) are fibroblastic mesenchymal neoplasms that harbour a genetic fusion of NAB2/STAT6. There are few reported cases in the central nervous system (CNS), of which spinal tumours are minority. We present a case of a 63-year-old woman with progressive paraparesis and a sensory level of T6. On the MRI we detected an intradural extramedullary lesion on T9-T10. We performed a laminectomy with an intraoperative ultrasound study in which we observed a heterogeneous lesion with an infiltrating pattern affecting the medulla at several points, and resection of the lesion. Immunohistological findings revealed positivity for vimentin, CD34 and STAT6; Ki-67 was 2%. A final diagnosis of SFT/HPC with SFT phenotype was made. SFT/HPC of the CNS is a rare neoplasm that should be taken into account in the differential diagnosis of these kinds of lesions, as clinical and MRI findings often lead to errors in diagnostic approach. The support of intraoperative ultrasound can assist in surgical decision-making.

Intramedullary spinal cord metastasis from pancreatic neuroendocrine tumor.

Intramedullary spinal cord metastasis (ISCM) is very rare and its optimal treatment remains controversial. Pancreatic neuroendocrine tumor (pNET) is a rare tumor that usually presents with hepatic metastasis. Hepatic failure due to tumor progression is the major cause of death in cases of pNET. To date, no report has described a case of ISCM from pNET. Although spinal cord metastasis of a solid tumor is uncommon, it is a critical condition that can cause a potentially irreversible loss of neurologic function. Here, we report the case of a 45-year-old man who presented with leg weakness and voiding difficulty, and was found to have ISCM from pNET. Surgical treatment prevented further neurological deterioration. This is the first case report of ISCM from pNET.

Melanotic schwannoma of the cervical spine progressing with pulmonary metastasis: case report.

Melanotic schwannoma (MS) is an unusual variant of nerve sheath neoplasm. Only 10% of these tumors will undergo malignant degeneration, with exceedingly rare reported metastasis. We present a 32-year-old woman with a 6-month history of cervical pain and left arm progressive weakness. Neurological examination showed a left upper limb radicular pain, with pyramidal syndrome at C5 level. The magnetic resonance imaging (MRI) study highlighted an intradural extramedullary heterogeneous mass along the spinal cord at the C4-C5 level, slightly hyperintense with T1 and hypointense with T2-weighted sequences, invading the left neural foramen. The patient underwent C3-C5 laminectomy with total resection of a black tumor. In the postoperative period, a patent deficit of shoulder abduction ensued related to the nervous section. Microscopically, compactly fascicles of spindle-shaped cells with pleomorphic and hypercromatic nuclei, dark brown intracellular pigments, as well as some mitotic figures were seen. Immunohistochemical stains for S-100, Human Melanoma Black-45 (HMB-45), and vimentin were positive, with Ki-67 Labelling Index (LI) of 15% compatible with MS. Six months after radiotherapy she presents local recurrence and lung metastatic dissemination of the MS. She underwent left pulmonary segmentectomy, followed by chemotherapy and radiosurgery. The patient developed a febrile neutropenia and worsening of general status, and died after 3 months due to respiratory complications. MS are rare tumors with potential for local recurrence and distal metastasis. Complete surgical resection remains as the treatment of choice, once the uncommon cases with malignant progression shows low response to chemo and radiotherapy.

Intramedullary subependymoma of the cervical spinal cord: a case report with immunohistochemical study.

Spinal subependymomas, which have a relatively benign nature, are very rare tumors. It is difficult to distinguish spinal subependymomas from other intramedullary spinal tumors based on neuroradiological findings. A case of cervical intramedullary subependymoma in a 63-year-old female is reported. The diffused enlargement of the spinal cord at C2 level involved the lesion with isointensity on a T1-weighted MRI and relatively high intensity on a T2-weighted MRI. Enhancement in the small part of the tumor was observed on a T1-weighted MRI with gadolinium administration. The tumor occupied the left side of the spinal cord, and was totally removed through a laminoplasty of C2. Immunohistochemistry was useful for pathological diagnosis. The clinical feature of this patient is described with the review of literatures.

Diffuse leptomeningeal glioneuronal tumors: a new entity?

The peculiar radiological and pathological findings of four pediatric cases admitted to the University Hospital of Padua between 1990 and 2007 are described. In all cases, the contrast-enhanced head and spine magnetic resonance images revealed thickened and abnormally enhancing subarachnoid spaces particularly at the level of basal cisterns and interhemispheric fissure. Furthermore, small cystic lesions scattered throughout the brain and mainly in the cerebellum were also visible. All patients were missing a well-defined intraparenchymal mass, although during the follow-up a small intramedullary lesion appeared within the cervical spine in two and subsequently in the frontal horn of the left lateral ventricle in one of those. All patients presented an indolent long-term follow-up. Histologically, the tumors were composed by a monotonous population of cells arranged in straight lines or in small lobules. The cells were characterized by round to oval nuclei with finely granular dispersed chromatin, inconspicuous nucleoli with oligodendrocyte-like features. The morphological and immunohistochemical findings suggested in all cases a "glioneuronal commitment" of the tumors. Because of the unique similar clinical and neuroradiological characteristics, we propose this small series of tumors as a new possible distinct pathological and clinical entity.

A rare case of malignant solitary fibrous tumor of the spinal cord.

STUDY DESIGN: Case report. OBJECTIVE: We present a case of an ambulatory patient with a solitary fibrous tumor of the spinal cord. SUMMARY OF BACKGROUND DATA: Solitary fibrous tumor (SFT) is an uncommon mesenchymal tumor of the pleural cavity, increasingly recognized at numerous extrathoracic sites, including, among others, prostate, kidney, and thyroid. The spinal cord is an extremely rare localization of SFTs with only 17 cases reported in the literature since 1996. Although SFTs are usually indolent neoplasms that are cured with complete surgical resection, malignant transformation has been described within histologically benign SFTs. However, no cases of malignant dissemination have been described in this localization. METHODS: Discussion of the patient's clinical and radiologic history with a review of the relevant background literature. RESULTS: We report the first case of spinal cord SFT with visceral dissemination years after the primary diagnosis, despite benign histologic features of the primary tumor. CONCLUSION: This finding may indicate that long-term follow-up might be necessary in these patients. In addition, metastatic radical surgery of SFTs should be considered to achieve long-term survival since there are no currently available effective systemic therapies.

Cellular neurofibroma with atypia mimics sarcoma: report of a case with immunohistochemical staining pattern analysis and literature review.

A case of two sporadic cellular neurofibromas with atypia and one widespread hyalinization neurofibroma of the lumbar spine in a 51-year-old man without evidence of neurofibromatosis-1 is reported. Cellular neurofibroma with atypia is an unusual variant. The definite criteria for low-grade and high-grade malignant peripheral nerve sheath tumors as well as cellular neurofibroma are not well defined in the literature. The clinical significance of atypical cellular neurofibroma has rarely been systematically studied. To our knowledge, the concomitance of cellular architecture and cytologic atypia is rarely documented, and this is a rare report of atypical cellular neurofibroma. The recognition of this entity is of great importance to both pathologists and clinicians because atypical cellular neurofibroma is clever at masquerading both histologically and cytologically as a sarcoma; therefore, a precise diagnosis of this variant is essential because of the differences in treatment and clinical behavior between benignancy and malignancy. We also examined the immunohistochemical characteristics of CD34 positive cells and focal high expression of p53 up to 73% encountered in our case. To our knowledge, seldom have series or case reports elucidated this phenomenon.

Polar spongioblastoma of the spinal cord: a case report.

"Rhythmic palisading" is a striking histologic pattern infrequently encountered in a variety of central nervous system (CNS) tumors. We present the case of an infant with a large spinal cord lesion wherein all sampled tissue showed columnar arrangements of palisaded cells, typical of polar spongioblastoma. The tumor was briskly proliferative, focally necrotic, and variably expressed S100, glial fibrillary acidic protein, neuron specific enolase, and p53 by immunohistochemistry. Fluorescence in situ hybridization failed to reveal isochromosome 17q, EGFR amplification, or deletions of 1p, 19q, 22q11.2, 10q, or p16. Despite chemotherapy and decadron, he developed lesional necrosis and intracranial metastases and died less than 1 mo from presentation. This case illustrates polar spongioblastoma as a distinctive histologic pattern that can occur in embryonal CNS tumors. Discrimination of these rare aggressive lesions from other CNS tumors with focal palisaded architecture is crucial as the treatment and prognosis of the latter may differ significantly.

An unusual progression of benign thoracic spinal cord teratoma in pregnancy: a hormonally-mediated pathway?

Intradural spinal cord teratoma is a very rare tumour that can be associated with dysraphism. The relationship of this lesion to pregnancy is unknown and its occurrence during pregnancy in the thoracic spine has not been previously reported. We report a 19-year-old pregnant woman with spinal dysraphism, who presented with a new onset thoracic myelopathy. The MRI scan showed an intradural, extramedullary lesion with solid and cystic component in the thoracic spine at the level of T5-T6. A thoracic laminectomy and excision of this lesion was followed by significant improvement of her lower limb function. Histopathology confirmed a benign mature teratoma. The rapid progression of this lesion during pregnancy suggests a hormonal mediated pathway for the tumour growth. Further analysis from the resected specimen confirmed that the tumour was oestrogen and progesterone receptors positive.

[BCL-2 in primary central nervous system lymphomas. Immunohistochemistry and molecular biology]. / La BCL-2 nei linfomi primitivi del sistema nervoso centrale. Immunoistochimica e biologia molecolare.

BCL-2 is a membrane protein known to be an apoptosis inhibitor. It is the product of the bcl-2 gene located on chromosome 18. Several different tumors show BCL-2 over-expression as result of a translocation or independently from it. More than 85% of follicular lymphomas and a smaller number of diffuse large cell B lymphomas contain t(14;18) (q32;q21). The aim of this study was to investigate the immunohistochemical expression of the BCL-2 protein and to ascertain, by means of traditional PCR (Polimerase Chain Reaction), its possible dependence from t(14;18) (q32;q21) in 9 primary central nervous system lymphomas. Six cases (67%) shoved immunohistochemical BCL-2 over-expression and 3 cases (33%) had t(14;18). Precisely: 2 cases (22%) had immunohistochemical BCL-2 over-expression and t(14;18) (q32;q21); 4 cases (44%) had BCL-2 over-expression without translocation; 1 case (11%) did not show diffuse BCL-2 over-expression in presence of the traslocation; the remaining 2 cases (22%) did not demonstrate BCL-2 over-expression or t(14;18) (q32;q21). In conclusion, our results indicate primary central nervous system lymphomas frequently show BCL-2 over-expression that in some case may be related to t(14;18) (q32;q21). Nevertheless, t(14;18) (q32;q21), as evaluated by traditional PCR, may not correspond to diffuse immunohistochemical BCL-2 positivity.

Choroid plexus carcinoma presented with spinal dysfunction caused by a drop metastasis: a case report.

A 2-year-old girl demonstrating gait disturbance and dysuria was evaluated and showed two large remote tumors at the left lateral ventricle and lower spinal canal. Pathological analysis demonstrated both of the tumors to be choroid plexus carcinoma (CPC) with high MIB-1 labeling index. The enhanced mitotic propensity would have contributed to an early stage of drop metastasis from the primary site to the sacral sac and following accelerated formation of a longitudinal tumor, which had grown in the subarachnoid space conforming to the spinal canal and finally caused the presenting symptoms of spinal dysfunction. This report shows that CPC can develop exophytically in the subarachnoid space as well as in the ventricle simultaneously before appearance of clinical symptoms and confirms the importance of extensive neuroimaging in its evaluation.

Subependymoma of the spinal cord and review of the literature.

Subependymoma is a tumor of the central nervous system, which frequently occurs in the ventricles and rarely in the spinal cord. Most of the intraventricular subependymomas are subclinical and thus incidentally encountered at autopsy, whereas the spinal ones are inevitably accompanied by myelopathy and are often diagnosed clinically as ependymomas or astrocytomas. Two cases of spinal cord subependymomas are reported, one of which recurred 9 years after the initial operation. All specimens of both cases showed similar microscopic features. Within a highly fibrillary background, round to ovoid tumor cells were unevenly distributed and arranged in cell clusters. Mitoses were rarely encountered. No necrosis was demonstrated in any of the specimens. Ultrastructural examination demonstrated many slender processes containing abundant intermediate filaments and occasional small lumen-like structures with many microvillous projections and cell junctions. Subependymomas arising in the spinal cord should be distinguished from other more aggressive gliomas, such as diffuse astrocytomas and ependymomas. Characteristic microscopic features and the ultrastructural studies support the diagnosis.

Leptomeningeal carcinomatosis after major remission to taxane-based front-line therapy in patients with advanced breast cancer.

AIM: To determine the incidence of leptomeningeal carcinomatosis (LMC), as the first manifestation of systemic progression, in breast cancer patients after obtaining a major response (complete response, CR or >80% partial response, PR) to first-line taxane-based chemotherapy treated between 1996 and 2000 in our Medical Oncology Unit. PATIENTS AND METHODS: Patients with histologically proven breast cancer having either metastatic disease, or high-risk locoregional disease that were entered into treatment protocols with first-line taxane (paclitaxel or docetaxel) plus anthracyclines or mitoxantrone combinations and developed LMC as the first evidence of progression after major response (CR or >80% PR) were analyzed in the present study (n = 155). RESULTS: Seven patients with a median age of 54 (range: 40-70) years developed LMC as their first evidence of progression after taxane-based regimens with a median interval of 6 months (range: 2-18) from start of treatment to diagnosis of LMC. Five patients received intrathecal (i.t.) methotrexate treatment and whole brain radiotherapy (RT), while one patient received i.t. methotrexate and RT to lumbar spine. Two patients responded to treatment for LMC, while two achieved stable disease and three progressed. Two patients had elevated cerebrospinal fluid tumor markers (more than serum marker levels) that proved useful in monitoring response to treatment. Median survival after LMC was 3.6 months (range: 1-31+) and correlated positively to the interval from the initiation of taxane-based therapy to LMC (r = 0.84, P = 0.019). Seven out of 86 responders (8.1%; 95% confidence interval, 2.4-13.9) developed LMC as the first sign of progression after a major response to first-line chemotherapy. CONCLUSIONS: LMC after a major response to front-line taxane-based regimens represents a grave disease manifestation and its incidence appears increased when compared in retrospect to non-taxane-treated patients. Prospective evaluation of the incidence of LMC after taxane versus non-taxane-based treatment from large randomized multiinstitutional trials is warranted and identification of potential prognostic factors might help identify patients requiring appropriate prophylactic therapy.