Ken-ichi Sato

Clinicopathologic Study of Pineal Parenchymal Tumors of Intermediate Differentiation

OBJECTIVEnPineal parenchymal tumors of intermediate differentiation (PPTID) are extremely rare tumor entities, and only limited data are available regarding their pathologic features and biologic behaviors. Because grading criteria of pineal parenchymal tumors (PPTs) have yet to be established, the treatment strategy and prognosis of PPTIDs remain controversial. We describe the clinicopathologic study of six patients with PPTID and compare responses for the treatment and prognosis with cases of pineocytoma (PC) and pineoblastoma (PB). From this analysis, we attempt to clarify the treatment strategy for PPTIDs.nnnMETHODSnThis study included 15 patients with PPTs, consisting of 6 PCs, 6 PPTIDs, and 3 PBs. We focused on the 6 patients with PPTIDs. All PPTID cases were treated surgically, and radiotherapy and chemotherapy were administered as adjuvant therapies in some cases. We have earlier reported the histopathologic study (Neuropathology 32:647-653, 2012). Briefly, we examined mitotic figures and necrosis by hematoxylin-eosin staining and immunohistochemical markers such as neuronal markers (synaptophysin, neurofilament (NF), and neuronal nuclear antigen), and an MIB-1 labeling index was determined.nnnRESULTSnIn the PPTID cases, the extent of resection was variable and the recurrence rates among patients varied according to stage and treatment. All PC patients underwent total resection with no recurrence. All PB patients underwent resection and adjuvant therapy with radiotherapy and chemotherapy. There were no recurrences in patients with PC or PB. The results of histopathologic findings have been already reported as mentioned above. Briefly, the results indicated no mitotic figure or necrosis in any of the six cases of PPTID, but those features were observed in PB cases. All cases even including PC and PB were immunopositive for neuronal markers. The MIB-1 labeling index of PPTID was 3.5%, whereas it was 0% in PC and 10.5% in PB.nnnCONCLUSIONSnGood radiosensitivity of PPTIDs was observed in our series. Because there are cases with discrepancies between images and pathologic findings, it is very difficult to determine the proper treatment strategy for PPTIDs. Proliferative potential was correlated with World Health Organization grade, although the immunoreactivity of neuronal markers did not correlate with the histologic grade.

A surgical technique with connective tissue repair for the management of subconjunctival orbital fat prolapse.

Subconjunctival orbital fat prolapse is an uncommon benign entity. In addition to insufficient information concerning the mechanisms of the prolapse, detailed surgical methods that can be followed are uncommon in the literature. We prospectively studied six consecutive eyes in four males who were to undergo our novel surgical sequence, attempting to avoid postoperative complications by reconstructing intermuscular septa on the basis of the assumption that the spontaneous prolapsed fat at the superior temporal quadrant stemmed from intraconal fat. Intraoperative findings were in agreement with our hypothesis that the anterior part of the herniated fat is covered by both the intermuscular septum and Tenon’s capsule. All the surgeries were uneventful and cosmetic improvement without postoperative complications was obtained. Our early results indicated the safety and efficacy of this newly developed technique for spontaneous orbital fat prolapse.

Radiation-induced osteosarcomas after treatment for frontal gliomas: a report of two cases.

Most radiation-induced osteosarcomas of the skull are reported to arise in the facial bone or paranasal sinus after radiotherapy for retinoblastoma and/or pituitary adenoma. Here we report two cases of radiation-induced osteosarcoma in the paranasal sinus after treatment for frontal glioma. Case 1 was a 56-year-old woman who underwent surgical resection of a left frontal tumor in October 1990. The histological diagnosis was a low-grade glioma, and radiotherapy of 54 Gy was administered. Sixteen years later, in September 2006, the patient noted an enlarging subcutaneous mass in the right frontal region. CT showed an osteolytic mass in the right frontal sinus. An open biopsy established the histopathological diagnosis of osteosarcoma, and the patient subsequently died of rapid tumor regrowth. Case 2 was a 58-year-old man who underwent partial removal of a bifrontal tumor in May 1996. The histological diagnosis was anaplastic oligoastrocytoma, and radiotherapy of 56 Gy was administered. Twelve years later, in March 2008, the patient was readmitted to our hospital for reasons of marked deterioration in general physical condition. Tumor recurrence was suspected in the left frontal lobe, and CT demonstrated an osteolytic mass in the left frontal and ethmoid sinus. A secondary operation was performed, and the pathological specimens were diagnosed as osteosarcoma. Radiotherapy was readministered, but the subject died of rapid tumor regrowth. From these clinicopathological findings, both cases were diagnosed as radiation-induced osteosarcoma. Radiation-induced osteosarcomas appeared 16 and 12 years after radiotherapy in cases 1 and 2, respectively. As the prognosis of radiationinduced osteosarcoma is poorer than that of primary osteo-sarcoma, careful attention is required for consideration of the long-term survival of patients with glioma.

[Clinicopathological Study of Pilomyxoid-Spectrum Astrocytomas:An Analysis of the BRAF Gene. Report of Two Cases].

In contrast to pilocytic astrocytomas(PAs), pilomyxoid astrocytomas(PMAs)demonstrate monophasic piloid cells with angiocentric distribution and a more aggressive clinical course. Recently, several reports have described combined histological features of both subtypes;accordingly, these were termed intermediate pilomyxoid tumors(IPTs). The KIAA1549-BRAF fusion gene has been found in approximately 70% of PAs, but is reportedly rare in PMAs. We describe a clinicopathological study of two patients with pilomyxoid-spectrum astrocytoma(PMSA). Case 1 was of a 29-year-old man who presented with a generalized seizure. Gadolinium-magnetic resonance imaging(Gd-MRI)demonstrated a less enhanced tumor in the left temporal lobe. Case 2 was of a 9-year-old boy who presented with headache. Gd-MRI revealed an irregularly enhanced tumor in the left cerebellum. In Case 1, the tumor showed monomorphous bipolar cells in a myxoid background and angiocentric arrangement;therefore, the diagnosis was PMA. In Case 2, part of the tumor had a myxoid, angiocentric pattern characteristic of PMA;the other part had a biphasic pattern characteristic of PA. PMA and PA were mixed in a 7:3 ratio;therefore, IPT was diagnosed. No BRAF V600E mutations were found by immunohistochemistry and sequencing in either case. Three major KIAA1549-BRAF fusion subtypes were analyzed by quantitative reverse transcription polymerase chain reaction(RT-PCR)and sequencing. No fusions were found in Case 1. However, K16-B9 fusion was identified in Case 2, and this fusion was more prevalent in the PA component than in the PMA component. In summary, no BRAF V600E mutations were found in PMSAs, but KIAA1549-BRAF fusion was identified in IPT, particularly in the PA component.

Adverse Effects of the Oral Anticancer Drug S-1: Lacrimal Passage Impairment and Specific Features of Corneal Epitheliopathy

We report the incidence of lacrimal passage impairment and specific features of corneal epitheliopathy as adverse effects of the oral anticancer drug S-1, and examine the relationship between the two pathologies. We conducted a retrospective chart review of 84 patients prescribed the anticancer drug S-1. The incidence of lacrimal passage impairment and corneal epitheliopathy was 8% and 6%, respectively. Three patients experienced both pathologies, demonstrating a moderate probability of both occurring in the same patient (kappa coefficient = 0.46). The findings show that lacrimal passage impairment and specific features of corneal epitheliopathy are likely to occur in the same individual as adverse effects of S-1.

[Pineal Parenchymal Tumor with Marked Cytologic Pleomorphism: Is there a Correlation with the Malignancy Grade?].

INTRODUCTIONnIn benign pineal parenchymal tumors (PPTs), namely, pineocytoma(PC)and PPT of intermediate differentiation (PPTID), cytologic pleomorphism has occasionally been found;however, it is controversial as to whether the presence of pleomorphic cells leads to upgrading of tumors. We experienced a rare case of pleomorphic PPT in an elderly woman and compared it with a retrospective series of 12 PPTs (PC:3, PPTID:6, pineoblastoma[PB]:3)to evaluate the correlation between pleomorphism and the malignancy grade. CASE AND MATERIALS: A 76-year-old woman presented with gradual cognitive deterioration and gait disturbance. Gadolinium-enhanced magnetic resonance imaging(Gd-MRI)revealed a small, enhanced tumor in the pineal gland with marked hydrocephalus. Endoscopic tumor biopsy and third ventriculostomy were performed simultaneously. The tumor was soft, pinkish, and slightly hemorrhagic. After the biopsy, the patient underwent gamma knife radiosurgery.nnnPATHOLOGICAL FINDINGSnThe PPT presented with areas of tumor cells forming pineocytomatous rosettes and areas of giant and multinucleated cells with hyperchromatic nuclei. Neither mitosis nor necrosis was observed. The tumor cells were positive for synaptophysin(SYN)and neurofilament(NF), but negative for glial fibrillary acidic protein(GFAP)and oligodendrocyte lineage transcription factor 2 (Olig2). The MIB-1 labeling index(LI)was 8.1%. There was no difference in the MIB-1 LI between pleomorphic and non-pleomorphic areas. All the 12 PPTs were immunopositive for the neuronal markers SYN and NF. The MIB-1 LI was 0% in PC, 3.5% in PPTID, and 10.5% in PB. The proliferative potential was correlated with the WHO grade. From these findings, the final diagnosis of this pleomorphic case was PPTID grade II, not PC, because the MIB-1 LI was relatively high, even though some tumor cells were forming pineocytomatous rosettes.nnnCONCLUSIONnAlthough cytologic pleomorphism in PPTs is generally considered not to be correlated with the malignancy grade, the final pathological diagnosis should be determined while considering the proliferative potential.

Subjective Signs of Rhegmatogenous Retinal Detachment Associated With Acute Posterior Vitreous Detachment

Despite recent anatomical successes of surgical treatment for rhegmatogenous retinal detachment (RRD), reattachment fails in 1.1-2.5% of cases [1-3]. In addition, even in cases of reattachment, some patients continue to show poor functional results [1, 2]. Prevention of RRD is therefore undoubtedly desirable. We retrospectively examined subjective signs in patients who underwent surgery for RRD to determine whether they could have received prophylactic laser treatment [4] at an early stage of retinal tear only or minimal retinal detachment. Subjects were 34 consecutive patients (34 eyes; 10 females; mean age ± SD: 58 ± 11 years) who presented with RRD associated with acute posterior vitreous detachment (PVD) on initial visit to Nikko Memorial Hospital. All patients subsequently underwent pars plana vitrectomy between April 2009 and March 2012; 3 were excluded due to complications related to obvious vitreous hemorrhage. Cases with traumatic or atopic RRD were not included. At the initial visit, patients were interviewed about subjective visual symptoms. Informed consent was obtained from all subjects prior to surgery and the study adhered to the tenets of the Declaration of Helsinki. Fourteen patients (41%) visited the hospital because of floaters only or visual field disturbance following floaters; the remainder visited due to visual field disturbance, presumably caused by RRD, with no experience of floaters. Only one patient complained of photopsia with initial floaters. Of those who initially experienced floaters, 2 patients took more than one month from onset to experiencing visual field disturbance (Fig. 1); this late-visit group was significantly younger than the other patients (P = 0.007, Welch’s t test). A significant proportion of patients with acute PVD complain of monocular floaters [5]. In the present study, we therefore considered the onset of floaters to be a potential sign of acute PVD. Patients also showing apparent vitreous hemorrhage on initial visit were excluded from the study because associated floaters may bias the patients’ actions in seeking a consultation. Of the patients without preceding floaters, approximately 60% visited due to visual field disturbance caused by RRD. As a result, it was too late to perform prophylactic laser treatment by the time the subjective symptoms led to consultation. In some of the relatively young patients with preceding floaters, there was quite a long period of time from onset of the initial floater to experiencing visual field disturbance. Since vitreous syneresis has yet to advance in the young generally [6], the tamponade effect of gel-state vitreous or weak vitreous contractions may result in late-onset RRD. Thus, consultation immediately after the onset of floaters might enable prophylactic laser photocoagulation to be performed at an early stage when only retinal tear or minimal retinal detachment has occurred. This suggests the importance of awareness of this state among the relatively young. Several studies suggest that patients with symptomatic PVD do not necessarily need scheduled reexamination if there are no pigmented cells in the vitreous, vitreous hemorrhage, or retinal hemorrhage at initial fundus examination [7-9]. Nevertheless, considering the potential for late-onset retinal breaks or RRD, it may be worth patients younger than 50 to schedule a follow-up examination after initial consultation. The study had certain limitations. This was a single-center