Cytology of Extraneural Metastases of Nonhematolymphoid Primary Central Nervous System Tumors: Six Cases with Histopathological Correlation and Literature Update.

INTRODUCTION: Extraneural/-cranial metastases (ENM) of primary central nervous system (CNS) tumors are rare and may be diagnostically challenging. We describe the cytomorphological and pertinent clinical features of ENM in a case series assessed by fine-needle aspiration (FNA). A search of the laboratory information systems of 2 tertiary care centers in Toronto (2000-2015) was performed. Cases with direct extracranial/-spinal extension of CNS neoplasms were excluded. Microscopic slides of FNA and surgical specimens were reviewed. Demographic and clinicopathological data were retrieved. CASE PRESENTATION: Six cases were identified with the original diagnoses of glioblastoma, glioblastoma with primitive neuroectodermal tumor-like components, anaplastic ependymoma, myxopapillary ependymoma, atypical meningioma, and hemangiopericytoma. Median patient age at first diagnosis was 44 years (range 22-56). The time interval between initial diagnosis and first metastatic disease manifestation was 3 months to 19 years. All FNA diagnoses were rendered correctly. In 4 cases, immunohistochemistry was used to support the diagnosis. All cases had prior surgical intervention at the primary tumor site. In 4 cases, the ENM location was the ipsilateral parotid or buccal area. Two primary tumors in midline location developed ENM in the scapular area. DISCUSSION/CONCLUSION: ENM are a rare manifestation of a range of different primary CNS tumors and may involve the ipsilateral head and neck mimicking clinically a salivary gland neoplasm. FNA can rapidly discriminate ENM from other, potentially more indolent conditions. Awareness of the clinical history is paramount to avoid diagnostic confusion.

Redefining Perineural Invasion: Integration of Biology With Clinical Outcome.

A diagnosis of perineural invasion (PNI), defined as cancer within or surrounding at least 33% of the nerve, leads to selection of aggressive treatment in squamous cell carcinoma (SCC). Recent mechanistic studies show that cancer and nerves interact prior to physical contact. The purpose of this study was to explore cancer-nerve interactions relative to clinical outcome. Biopsy specimens from 71 patients with oral cavity SCC were stained with hematoxylin and eosin and immunohistochemical (IHC; cytokeratin, S100, GAP43, Tuj1) stains. Using current criteria, PNI detection was increased with IHC. Overall survival (OS) tended to be poor for patients with PNI (P = .098). OS was significantly lower for patients with minimum tumor-nerve distance smaller than 5 µm (P = .011). The estimated relative death rate decreased as the nerve-tumor distance increased; there was a gradual drop off in death rate from distance equal to zero that stabilized around 500 µm. In PNI-negative patients, nerve diameter was significantly related to OS (HR 2.88, 95%CI[1.11,7.49]). Among PNI-negative nerves, larger nerve-tumor distance and smaller nerve diameter were significantly related to better OS, even when adjusting for T-stage and age (HR 0.82, 95% CI[0.72,0.92]; HR 1.27, 95% CI[1.00,1.62], respectively). GAP43, a marker for neuronal outgrowth, stained less than Tuj1 in nerves at greater distances from tumor (OR 0.76, 95% CI[0.73,0.79]); more GAP43 staining was associated with PNI. Findings from a small group of patients suggest that nerve parameters other than presence of PNI can influence outcome and that current criteria of PNI need to be re-evaluated to integrate recent biological discoveries.

Relationship between neural alteration and perineural invasion in pancreatic cancer patients with hyperglycemia.

BACKGROUND: Patients with higher levels of fasting serum glucose have higher death rates from pancreatic cancer compared to patients with lower levels of fasting serum glucose. However, the reasons have not been studied. The goal of the current study was to examine the neural alterations in pancreatic cancer patients with hyperglycemia and to identify the relationship between the neural alterations and perineural invasion. METHODOLOGY/PRINCIPAL FINDINGS: The clinical and pathological features of 61 formalin-fixed pancreatic cancer specimens and 10 normal pancreases as controls were analyzed. Furthermore, the expression of Protein Gene Product 9.5 (PGP9.5), Myelin P0 protein (MPP), NGF, TrkA, and p75 were examined by immunohistochemistry. The median number of nerves, the median area of neural tissue, and the median nerve diameter per 10 mm(2) were larger in the hyperglycemia group than those in the euglycemia group (p = 0.007, p = 0.009, and p = 0.004, respectively). The integrated optical density (IOD) of MPP staining was lower in the hyperglycemia group than those in the euglycemia group (p = 0.019), while the expression levels of NGF and p75 were higher in the hyperglycemia group than those in the euglycemia group (p = 0.002, and p = 0.026, respectively). The nerve bundle invasion of pancreatic cancer was more frequent in the hyperglycemia group than in the euglycemia group (p = 0.000). CONCLUSIONS/SIGNIFICANCE: Nerve damage and regeneration occur simultaneously in the tumor microenvironment of pancreatic cancer patients with hyperglycemia; the simultaneous occurrence may aggravate the process of perineural invasion. The abnormal expression of NGF and p75 may also be involved in this process and subsequently lead to a lower rate of curative surgery.

Morbidity and functional status of patients with pelvic neurogenic tumors after wide excision.

BACKGROUND: We previously reported that over the last 10 years our practice has evolved in the treatment of neurogenic tumors of the pelvis to include a multispecialty team of surgeons, a factor that might decrease morbidity and improve recurrence, survival, and function. QUESTIONS/PURPOSES: Therefore, we (1) assessed the morbidity associated with surgical excision in patients with neurogenic tumors of the pelvis; (2) determined the function of these patients; and (3) determined the rates of local recurrence, metastasis, and overall survival with this new approach. METHODS: We reviewed the records of all 38 patients who had surgery for a pelvic plexus tumor between 1994 and 2005. Twenty one were male. The mean age of all patients was 38 years and median follow up was 2.1 years. Twelve patients had a malignant tumor. We recorded demographic data, postoperative complications, tumor-specific recurrence, and determined survival. RESULTS: Postoperative complications occurred in nine of the 38 patients (23%): hematoma (n = 3), wound infection or deep abscess (n = 3), and deep venous thrombosis (n = 3). Surgical complications occurred more frequently in patients with malignant disease. Patients with benign tumors had a mean MSTS score of 94%, while survivors of malignant disease had a mean of 57%. For malignant tumors, the 5-year rate of local recurrence was 40%, the estimated 5-year rate of metastasis was 67% and 5-year survival rate was 50%. CONCLUSION: Using a team approach, surgical excision provided high functional scores for patients with benign disease with a low rate of complications. In patients with malignant tumors, intentional wide resection is associated with higher morbidity but yields acceptable functional scores.

Differential diagnosis in patients with ring-like thallium-201 uptake in brain SPECT.

UNLABELLED: This study was performed to investigate lesions with ring-like thallium-201 (201Tl) uptake and to determine whether SPECT provides any information in differential diagnosis. METHODS: A total of 244 201Tl SPECT images were reviewed. In each study, early (15 min postinjection) and late (3 hr) brain SPECT images were obtained with 111 MBq of 201Tl. The early uptake ratio (ER; lesion to normal brain average count ratio) and the late uptake ratio (LR) and the L/E ratio (ratio of LR to ER) were calculated. RESULTS: Ring-like uptake was observed in pre-therapeutic 26 SPECT images, including ten glioblastoma multiformes (ER, 3.45 +/- 0.64; LR, 2.74 +/- 0.54; L/E ratio 0.80 +/- 0.13), five meningiomas (6.48 +/- 2.34; 4.41 +/- 1.41; 0.72 +/- 0.19), four metastatic lung cancers (3.47 +/- 1.23; 2.40 +/- 0.98; 0.70 +/- 0.14), four brain abscesses (2.48 +/- 1.06; 1.59 +/- 0.30; 0.78 +/- 0.15), one invasive lesion of squamous cell carcinoma from the ethmoid sinus (1.54; 1.52; 0.99), one medulloblastoma (3.53; 3.52; 1.00) and one hematoma (3.32; 2.36; 0.71). The ER of meningioma was significantly higher than those of glioblastoma multiforme (p < 0.0005), metastatic lung cancer (p < 0.005) and brain abscess (p < 0.0005). There were no significant differences among these three entities. The LR of meningioma was significantly higher than those of glioblastoma multiforme (p < 0.005), metastatic lung cancer (p < 0.005) and brain abscess (p < 0.0001). The LR of brain abscess was significantly lower than that of glioblastoma multiforme (p < 0.05). The L/E ratio could not differentiate these four entities. CONCLUSION: High ER and high LR in a lesion with ring-like uptake is likely an indicator of meningioma. The LR of brain abscess was significantly lower than that of glioblastoma multiforme, but 201T1 SPECT has still difficulty in differentiating abscess from brain tumor.

Prognostic value of thoracic recurrent nerve nodal involvement in esophageal squamous cell carcinoma.

BACKGROUND: The determination of a simple and reliable prognostic factor that allows identification of patients at high risk of early cancer recurrence and subsequent death after resection of esophageal carcinoma should contribute to more accurate management of patients suffering from this disease. STUDY DESIGN: The aim of this study was to assess the prognostic value of thoracic recurrent nerve nodal involvement after curative resection of esophageal squamous cell carcinoma. The prognostic importance of gender, age, tumor penetration, and extent of lymph node involvement was evaluated in 55 patients after curative resection of esophageal squamous cell carcinoma. RESULTS: Thirty-four of 55 patients (62%) had nodal metastases and 10 of 55 (18%) had thoracic recurrent nerve nodes involved. The median overall survival was 28 months. By univariate analysis, survival was higher in association with the absence of adventitial invasion (p = 0.04), of nodal involvement (p = 0.03), and of thoracic recurrent nerve nodal involvement (p = 0.0001). In a Cox proportional hazards regression model, thoracic recurrent nerve nodal involvement appeared the strongest predictive factor (adjusted hazard ratio 8.4 (3.0-23.7)). CONCLUSIONS: Assessment of thoracic recurrent nerve nodes is appropriate to identify patients who are at high risk of disease-related death after surgical resection.

Perineural infiltration by cutaneous squamous cell carcinomas of the head and neck.

In this paper six cases of cutaneous squamous cell carcinoma of the head and neck region with histologically-documented perineural tumoral infiltration are presented. Most patients showed recurrent disease during follow-up and have been treated with surgery and radiotherapy with or without systemic chemotherapy. The prognostic implications of perineural neoplastic infiltration as well as of therapeutic options are discussed.

Fine needle aspiration cytology of primitive neuroectodermal tumors. A report of these cases.

Primitive neuroectodermal tumor (PNET) is a small round cell malignancy arising in soft tissue and bone, predominantly in older children and adolescents. We report the cytomorphologic features and findings of ancillary studies of eight fine needle aspiration (FNA) biopsies from three patients (7-year-old male, 12-year-old female, 9-year-old female). Two of the biopsies suggested the initial diagnosis of PNET of the chest wall, while the remaining six documented recurrent or metastatic disease. In one of these cases the primary diagnosis made by FNA biopsy enabled the pediatric oncologists to give specific therapy for the unresectable tumor and achieve remission. Local recurrences included the chest wall (two cases), pleura (one case) and pericardium (one case), while metastatic disease involved the supraclavicular lymph node and breast. All the cases consisted of small malignant cells with a high nuclear/cytoplasmic ratio and hyperchromatic nuclei without prominent nucleoli. Homer Wright rosettes were seen in only two of the aspirates, and neuropil and ganglion cells were not present. Ancillary studies, including electron microscopy (two cases), immunocytochemistry (four aspirates from two cases) and cytogenetics (11/22 translocation, one case) performed on the aspirated material were aids in making a specific diagnosis and excluded other small round cell tumors of childhood, such as malignant lymphoma, rhabdomyosarcoma and Ewing's sarcoma. The differential diagnosis between PNET and neuroblastoma can be difficult on the basis of an FNA biopsy alone, although light microscopic morphologic differences exist. Clinical features (e.g., age, primary site, metastatic patterns), catecholamine levels, electron microscopy and cytogenetics are necessary in establishing the correct diagnosis.

Intraventricular mass lesions of the brain: CT and MR findings.

One tenth of all CNS neoplasms involve the ventricles of the brain. These mass lesions are located in areas that are difficult to reach surgically, and because they are intraventricular, spread via the CSF is common. CT and MR imaging have been useful in demonstrating these masses, but imaging characteristics are usually nonspecific. The location of the mass and the patient's age provide the most helpful information in the differential diagnosis.

Ophthalmic manifestations of perineural spread of facial skin malignancy.

Facial skin malignancy, when complicated by perineural spread (PNS), can lead to devastating orbital, intracranial and paranasal sinus involvement, the management of which requires a multidisciplinary approach and which itself may be devastating. Adequate surgical excision with frozen section control, and specific inspection of histological specimens for perineural invasion, are essential to avoid this problem. This report presents four patients who manifested such involvement, and emphasises the importance of recognition of such ominous symptoms as facial pain, paraesthesiae and weakness. Thorough neuro-ophthalmic examination is mandatory to detect signs of nerve involvement which may indicate perineural spread both at the initial assessment of primary tumour and at suspected recurrence. In this series, the most common sensory and motor nerves affected were, respectively, single, small branches of the ophthalmic and facial nerves.

Ultrastructure of capillary walls in human brain tumors.

Changes in capillary walls between human glial, non-glial and metastatic brain tumors were studied with conventional ultrathin section and freeze-fracture replica techniques. The following results were obtained. (1) In glial tumors, ultrathin section studies showed cell junctions of the capillaries were either short or elongate. Moreover, endothelial hyperplasia, surface infolding of endothelial cells, irregularity of the basal lamina and a large extravascular space were observed. Freeze-fracture replicas of capillary endothelium showed tight junctions as two to seven strands. In addition, pinocytotic vesicles had increased markedly and were an average of 25 per microns 2. Both ultrathin and freeze fracture studies showed that, in contrast to malignant gliomas, there were only slight changes in benign astrocytomas. (2) In non-glial tumors, ultrathin sections showed surface infoldings, increased vesicles, many fenestrations of endothelial cells, irregularity of basal lamina and enlarged perivascular space. Freeze-fracture replicas of vascular endothelium, showed that the average number of pinocytotic vesicles and fenestrations were 25 and 22 per microns 2, respectively. Moreover, the tight junction was composed of one or two strands which appeared to be a discontinuous array of particles. (3) In metastatic brain tumors, ultrathin studies showed capillary endothelia were proliferated, had marked infolding, and showed an increased number of pinocytotic vesicles and many fenestrations. Moreover, short and elongate intercellular junctions were presented but no open junction was detected. Finally the basal lamina lost its three-layered appearance and was irregular in width. Freeze-fracture replicas showed pinocytotic vesicles had increased and were 24 per microns 2 on average in four cases, but fenestrations and tight junctions could not be detected. The most fundamental feature of vessels in these three different kinds of tumors was whether they were fenestrated or not. Glial tumors were non-fenestrated, whereas non-glial and metastatic tumors were fenestrated.

Spinal metastases. A rare mode of presentation of brain tumors.

An analysis of more than 18,000 primary central nervous system (CNS) tumors revealed only 18 cases (0.01%) in which dropped spinal metastases had caused the presenting symptoms. This group included 11 males and 7 females in whom there was no history of surgical intervention or irradiation. Primitive neuroectodermal tumors ( PNET , medulloblastoma), comprised the largest group (11 patients) followed by high-grade astrocytomas (anaplastic and glioblastoma) (5 patients). One case each of germinoma and ependymoma were also identified. The clinicopathologic data of these cases, and a brief review of the literature are presented.

[Radiographic findings of periosteal reactions in systemic bone disorders (author's transl)]. / Röntgenmorphologie der Periostregion bei Osteopathien.

Periosteal reaction is frequently the first sign of systemic disease affecting the skeleton, including generalized osteopathia. It can be generalized, focal, monostotic or polyostotic and shows solid, lamellary or interrrupted spiculae-like reaction. A reliable diagnosis is possible from the interpretation of these changes, as for instance with spiculae: Very dense and evenly arranged spiculae are only seen in hemolytic anemias and metastases of neurogenic tumors. Onionskin like periosteal reaction with simultaneous transformation of the diaphyseal cortex are difficult to interpret. However, in case of hyperparathyreoidism, subperiosteal resorption and transformation of the diaphyseal cortex permit precise diagnosis. Follow-up examinations have prognostic and therapeutic value. The knowledge of the different morphology of periosteal reaction associated with systemic disease (including generalized osteopathias) is important in diagnostic radiology.