Ioannis G. Koutlas

Design of an MRI-Compatible Robotic Stereotactic Device for Minimally Invasive Interventions in the Breast†

The objective of this work was to develop a robotic device to perform biopsy and therapeutic interventions in the breast with real-time magnetic resonance imaging (MRI) guidance. The device was designed to allow for (i) stabilization of the breast by compression, (ii) definition of the interventional probe trajectory by setting the height and pitch of a probe insertion apparatus, and (iii) positioning of an interventional probe by setting the depth of insertion. The apparatus is fitted with five computer-controlled degrees of freedom for delivering an interventional procedure. The entire device is constructed of MR compatible materials, i.e. nonmagnetic and non-conductive, to eliminate artifacts and distortion of the MR images. The apparatus is remotely controlled by means of ultrasonic motors and a graphical user interface, providing real-time MR-guided planning and monitoring of the operation. Joint motion measurements found probe placement in less than 50 s and sub-millimeter repeatability of the probe tip for same-direction point-to-point movements. However, backlash in the rotation joint may incur probe tip positional errors of up to 5 mm at a distance of 40 mm from the rotation axis, which may occur for women with large breasts. The imprecision caused by this backlash becomes negligible as the probe tip nears the rotation axis. Real-time MR-guidance will allow the physician to correct this error Compatibility of the device within the MR environment was successfully tested on a 4 Tesla MR human scanner

Synchronous neural interactions assessed by magnetoencephalography: a functional biomarker for brain disorders

We report on a test to assess the dynamic brain function at high temporal resolution using magnetoencephalography (MEG). The essence of the test is the measurement of the dynamic synchronous neural interactions, an essential aspect of the brain function. MEG signals were recorded from 248 axial gradiometers while 142 human subjects fixated a spot of light for 45-60 s. After fitting an autoregressive integrative moving average (ARIMA) model and taking the stationary residuals, all pairwise, zero-lag, partial cross-correlations (PCC(ij)(0)) and their z-transforms (z(ij)(0)) between i and j sensors were calculated, providing estimates of the strength and sign (positive, negative) of direct synchronous coupling at 1 ms temporal resolution. We found that subsets of z(ij)(0) successfully classified individual subjects to their respective groups (multiple sclerosis, Alzheimers disease, schizophrenia, Sjögrens syndrome, chronic alcoholism, facial pain, healthy controls) and gave excellent external cross-validation results.

Plexiform schwannoma: a clinicopathologic overview with emphasis on the head and neck region

Plexiform schwannoma is a rare variant of Schwann cell tumor. Occurring in either conventional or cellular type, they are characterized either grossly or histologically by a plexiform pattern of intraneural growth often with multinodularity. Ordinary as well as plexiform schwannoma typically arise in superficial soft tissues and show a predilection for the head and neck region. Infrequent examples arise in the setting of neurofibromatosis type 2 or schwannomatosis. The purpose of this study was to assess the frequency of plexiform schwannoma by location, to determine their syndromic association, and to analyze the clinicopathologic features of tumors affecting the head and neck region. It was found, in this not entirely random population, that plexiform schwannoma represented 4.3% of all schwannomas, 23% of head and neck region examples, 15% of cutaneous schwannomas, and lastly, 2% of 322 oral nerve sheath tumors made separately available for review. Furthermore, the association with neurofibromatosis type 2 and with schwannomatosis was 5% each.

Intravascular papillary endothelial heperplasia of the oral soft tissues: Report of 18 cases and review of the literature

Abstract Purpose : Intravascular papillary endothelial hyperplasia (IPEH) is a benign, nonneoplastic, vascular lesion, that is characterized histologically by papillary fronds lined by proliferating endothelium: it is thought to represent an unusual form of organizing thrombus. It may develop in a distended vessel or in association with other vascular lesions. The main significance of IPEH is its microscopic resemblance to angiosarcoma and possible misinterpretation as such. Methods : We report the clinicopathologic features of 18 examples of IPEH of the oral soft tissues and lips, and review such features of 55 previously reported oral cases. Results : The lips and tongue were most frequently involved and a female predilection was evident. Histologically, the pure form of IPEH was more commonly encountered. Conclusion : The differential diagnosis and possible histogenesis of the lesion are discussed.

Perivascular epithelioid cell tumor of the oral mucosa

Perivascular epithelioid cell tumors (PEComas) are a family of tumors defined by the coexpression of melanocytic and muscle markers. Examples have been reported in many organs, soft tissues, and bone. Further expanding the list of locations, we report a case arising in the hard palate. Histologically, the tumor was composed of large elongated or epithelioid cells with granular cytoplasm. Immunohistochemically, tumor cells were positive for HMB-45, Melan A/MART-1, CD10, smooth muscle actin, desmin, and calponin. Ultrastructural examination revealed stage I melanosomes, thin filaments, and dense plaques. Recurrence has not been reported after 20 months. To our knowledge, this is the first detailed description of an intraoral PEComa.

Sclerosing odontogenic carcinoma: a previously unreported variant of a locally aggressive odontogenic neoplasm without apparent metastatic potential.

We describe 3 cases of apparent odontogenic carcinomas that share histologic features not previously reported in the literature. The tumors involved one 72-year-old man and 2 women, 46-year old and 73-year old, respectively. Two cases occurred in the mandible and 1 in the maxilla. The tumors presented as expansile radiolucencies. Histopathologically, they were characterized by small nests and thin cords of small cuboidal or polygonal epithelial cells, featuring, only focally, cytoplasmic clearing. Pleomorphism was not remarkable and mitoses were extremely rare. The most striking feature of malignancy was skeletal muscle and perineural infiltration. Sclerosis of the stroma was remarkable. Immunohistochemically, all tumors stained for cytokeratins (CK) 5/6, CK19, and ϵ-cadherin, the latter exhibiting a fragmented cytoplasmic membranous staining. Positive nuclear staining was obtained with p63. Focal staining for CK7 was seen in 1 case. All tumors were negative for CK20, carcinoembryonic antigen, and CAM5.2. The patients were surgically treated and one of them received adjuvant radiation. Microscopic tumor nests and cords were found far beyond of what surgically seemed to be tumor-free margins. All patients are free of disease 5, 12, and 4 years after treatment, respectively. We propose the name sclerosing odontogenic carcinoma. As current classifications of odontogenic tumors do not include such examples, it is important that pathologists become aware of this entity. Finally, this report supports recent literature on positive nuclear p63 in odontogenic cysts and tumors.

Arteriovenous hemangioma: a clinicopathological and immunohistochemical study

The clinicopathological and immunohistochemical properties of 6 examples of arteriovenous hemangioma, including 2 intraoral lesions, were reviewed. This distinct benign, acquired vascular lesion, infrequently encountered in the literature, is characterized by multiple thick‐ and thin‐walled vascular spaces resembling arteries and veins, respectively. In our study, we performed elastic stains that revealed a prominent venular component, whereas the arterial aspect was inconspicuous to absent. Our aim was also lo elucidate the possible histogenesis of this lesion. Previous reports suggest as pathogenetic mechanisms hamartomatous proliferation either of the subpapillaiy vascular plexus or of the Suquet‐Hoyer canal of the true glomus. Our immunohistochemical studies failed to identify typical glooms cells. In addition, we investigated the mast cell count in all lesions and it was found increased. These findings, as well as recent evidence directly implicating mast cells in angiogenesis, can support the theory of hamartomatous proliferation of the subpapillary plexus. One should also not exclude the possibility of a reactive process resulting in the characteristic features of arteriovenous hemangioma.

Development of a robotic device for MRI-guided interventions in the breast

The objective of this work was to develop a robotic apparatus for MR-guided biopsy and therapeutic interventions in the breast. This device facilitates (i) conditioning of the breast, by setting the orientation and degree of compression, (ii) definition of the interventional probe trajectory, by setting the height and angulation of a probe guide and (iii) positioning of an interventional probe, by setting the depth of insertion. The apparatus is fitted with appropriate computer-controlled degrees of freedom for optimal approach for delivering and monitoring interventions with MR-guidance, such as diagnostic or therapeutic trans-cannula or subcutaneous minimally invasive procedures. The entire device is constructed of MR compatible material, i.e. non-magnetic and non-conductive, to eliminate artifacts and distortion of the local magnetic field. The apparatus is remotely controlled by means of ultrasonic actuators and a graphics user interface, providing real-time MR-guided planning and monitoring of the operation.

Oral Hairy Leukoplakia in HIV-Negative Patients: Report of 10 Cases

Ten cases of oral hairy leukoplakia (OHL) in HIV- negative patients are presented. Eight of the 10 patients were on steroid treatment for chronic obstructive pulmonary disease, 1 patient was on prednisone as part of a therapeutic regimen for gastrointestinal stromal tumor, and 1 patient did not have any history of immunosuppression. There were 5 men and 5 women, ages 32-79, with mean age being 61.8 years. Nine out of 10 lesions were located unilaterally on the tongue, whereas 1 lesion was located at the junction of the hard and soft palate. All lesions were described as painless, corrugated, nonremovable white plaques (leukoplakias). Histologic features were consistent with Epstein—Barr virus—associated hyperkeratosis suggestive of OHL, and confirmatory in situ hybridization was performed in all cases. Candida hyphae and spores were present in 8 cases. Pathologists should be aware of OHL presenting not only in HIV-positive and HIV-negative organ transplant recipients but also in patients receiving steroid treatment, and more important, certain histologic features should raise suspicion for such diagnosis without prior knowledge of immunosuppression.

Acinic cell carcinoma of minor salivary glands: a clinicopathologic study of 21 cases.

PURPOSE Acinic cell carcinoma (ACC) is an infrequent type of malignant salivary gland tumor. Approximately 16% of all ACCs occur in the mouth according to several small studies. This study was undertaken to 1) report on the clinicopathologic characteristics of 21 intraoral examples, 2) reconfirm the reported indolent behavior of these tumors, and 3) verify the synchronous or metachronous occurrence of other malignancies with ACC. MATERIALS AND METHODS Twenty-one patients with intraoral ACC were identified in the previous 27 years. Demographic data and histomorphologic characteristics were evaluated and follow-up information was sought. RESULTS Fifteen patients (68%) were male and 6 female. Seven cases (33.3%) occurred in the buccal mucosa, 6 in the palate (28.6%), 5 involved the upper lip (23.8%), 2 the retromolar mucosa (9.5%), and 1 the lower lip (4.8%). The mean age of patients was 50 years, with the youngest being 13 and the oldest 73. The duration was known in 9 patients and varied from 4 months to longer than 15 years. The size of the tumors varied from 0.6 to 1.6 cm. Where reported, lesions were asymptomatic. Histologically, different patterns that included microcystic, papillary cystic, follicular and solid, and combinations of these types characterized the lesions. Follow-up information was obtained in 12 patients. Eleven patients did not report recurrence or metastatic disease. The follow-up extended from 10 months to 17 years. One patient had 2 recurrences due to erroneous diagnosis that led to inappropriate treatment. After properly diagnosed and treated, this patient has been free of tumor for 4 years. Of interest were the metachronous occurrence of lymphoma in 1 patient and the synchronous occurrence of renal cell carcinoma in another. CONCLUSION This study confirms the indolent behavior of ACC of minor salivary glands and previous reports on the occasional synchronous or metachronous association of malignant salivary gland tumors with other malignancies.