Papillary tumor of the pineal region

Primary pineal gland malignancies are uncommon and seldom have papillary architecture. We report a case of a 22‐year‐old male patient who presented with progressive headache, horizontal nystagmus and worsening diplopia. MRI of the brain showed a lesion in the pineal region. The patient was taken for resection of the lesion which was classified as papillary tumor of pineal region (PTPR). Histologically, the neoplasm was cellular, characterized by eosinophilic cells with indistinct borders, large pleomorphic nuclei, numerous apoptotic figures without necrosis or microvascular proliferation. Prominent perivascular pseudorosettes were seen. Diffuse immunoreactivity for cytokeratin 8–18 was noted. Synaptophysin antibody showed membranous and cytoplasmic positivity. Weak staining for GFAP, vimentin, S‐100 protein, and neuron specific enolase (NSE) were observed only focally. This is a case report of this rare pineal region neoplasm which only recently has been described as a histopathologic entity. Although the clinicopathological characteristics of this tumor are not entirely understood, a brief review of the literature as well as our contribution suggest an indolent neoplasm with a tendency for local recurrence. Histologically, PTPR demonstrates a unique assortment of epithelial, ependymal, and neuroendocrine features. The differential diagnosis of papillary neoplasms of the pineal region is reviewed.     

Pleomorphic pineocytoma associated with normal pineal parenchyma: Report of a case in a 70‐year‐old man

Pineocytomas (PCs) most frequently occur in adults, but only three cases have been reported in women older than 70 years. In PCs, cytologic pleomorphism, accompanied by ganglion cells intensely expressing neuronal markers, has been described and the presence of pleomorphic cells may lead to an erroneous upgrading of the tumor. We report an unusual case of pleomorphic pineocytoma in an older patient who presented with a slowly growing tumor adjacent to residual pineal gland. The immunohistological markers of the tumoral tissue and the remnant normal pineal tissue were evaluated and compared. In the neoplasm, the large number of cells labeled for neuronal markers, including many pleomorphic cells, confirmed previous findings that a neuronal immunophenotype is common in PC. Reactivity for synaptophysin was stronger in the tumor than the pineal gland, whereas neurofilament protein reactivity was stronger in the pineal gland than the tumor. The neoplastic cells, but not the pineal gland, were reactive for chromogranin A. This dense core vesicle‐associated protein immunolabeling is an interesting diagnostic marker for PCs, which makes it possible to distinguish normal pineal parenchyma with low or negative expression from tumoral tissue. This case illustrates that, even though PCs are low‐grade tumors, they can increase in size and surgery appears a valuable option.     

Long-term survival in malignant intracranial germ-cell tumors: a report of two cases and a review of the literature

The authors report the successful treatment of two cases of malignant germ-cell tumor. A 12-year-old patient with a pineal immature teratoma and increase of -fetoprotein serum levels was treated with total excision and cisplatin, vinblastine, and bleomycin (PVB) in combination given twice. One year later, he had a recurrence of tumor in the right occipital lobe, which was totally removed, and yolk sac tumor was verified. As subsequent adjuvant chemotherapy, PVB was given in four courses over 1.5 years, together with one course of cisplatinetoposide (PE) therapy. The patient is well 5 years and 9 months after the first operation. In the second case, a 19-year-old patient with a pineal mixed germ-cell tumor, composed of germinoma, yolk sac tumor, and embryonal carcinoma, was treated with total excision, followed by four courses of PVB therapy and one of PE. She has done well in the 4.5 years since the initial treatment. Thus, aggressive extirpation of the lesion and subsequent combination chemotherapy using cisplatin and other multiple drugs, given in at least four courses over 1.5 years, even if tumor markers return to within normal limits, might provide successful treatment for malignant germ-cell tumors.     

原发性眶内卵黄囊瘤:病例报告并文献分析

目的 探讨临床少见原发于眶内卵黄囊瘤的病理学特征.并讨论颅内生殖细胞肿瘤的病理学鉴别要点.方法 分析l例原发于左侧眶尖卵黄囊瘤患儿的临床表现.HE和免疫组织化学染色观察颅内卵黄囊瘤的临床病理学特点及免疫表型.结果 患者男性.2岁.表现为左眼上睑下垂并眼球突出.MRI显示颅底肿瘤侵犯左侧后组筛窦、眼眶及翼窝并蝶骨翼板,左侧上颌窦后壁、筛骨及眼眶尖部骨质破坏,与硬膜分界尚清,未突破硬膜向脑实质浸润.术中可见肿瘤位于眶尖区之眶内外,累及左侧海绵窦区,位于硬膜外尚未侵入硬膜下区,无包膜,破坏眶尖区骨质,长人蝶窦和筛窦.肿瘤组织由许多相互交通的间隙形成疏松的网状结构,衬覆胞质透亮的圆形或多边形细胞,核深染、不规则且核仁突出,核分裂象多见;可见Schiller-Duval(S-D)小体结构.为单个圆形或长形乳头状结构,含有单个血管的纤维血管轴心,被覆柱状细胞,乳头占据的间隙衬覆立方、扁平或"鞋钉"样细胞;肿瘤细胞内或细胞间可见嗜伊红且PAS阳性透明小体.肿瘤细胞弥漫表达细胞角蛋白,灶性表达甲胎蛋白、CD99和CD117,但不表达CD30、CD45、胎盘碱性磷酸酶、突触素、嗜铬素A和CD34.连续组织切片HE染色未发现合并其他类型生殖细胞肿瘤.病理诊断左侧眶尖原发性卵黄囊瘤(WHOⅣ级).结论 颅内卵黄囊瘤好发于青少年,多生长于中线结构,具有特殊的组织学构象和免疫组织化学表型,预后不良,诊断时应与其他生殖细胞肿瘤相鉴别,并注意是否同时合并其他生殖细胞肿瘤成分.     

Papillary tumor of pineal region presenting with leptomeningeal seeding

Papillary tumor of the pineal region (PTPR) is a recently recognized and rare pineal tumor, presenting as a solitary mass with or without hydrocephalus. Here, we report a case of c‐Kit expressing PTPR with leptomeningeal seeding. A 39‐year‐old woman presented with a 1‐month history of headache and decreased visual acuity. MRI showed a large, 4 cm‐diameter solid and cystic enhancing mass at the pineal region with associated ventriculomegaly. Smaller nodular lesions were also found at the pituitary stalk and bilateral internal acoustic canal (IAC). The leptomeninges were noted to be enhanced with gadolinium. Endoscopic third ventriculostomy and partial resection were performed. The specimen was small in quantity but nonetheless, revealed the typical features of PTPR, which were tumor cells with vacuolated cytoplasm forming a pseudopapillary architecture. The tumor cells were diffusely immunoreactive for vimentin, INI‐1 and c‐Kit, focally immunoreactive for neuronal specific enolase (NSE) and S100 protein but negative for cytokeratin, epithelial membrane antigen (EMA), synaptophysin and GFAP. Ultrastructurally, the tumor cells revealed variably‐sized cytoplasmic vacuoles, intermediate filaments and villous cytoplasmic membrane. With these features, a diagnosis of PTPR was rendered. The lesions at the pineal gland and bilateral IAC were irradiated through gamma knife radiosurgery and a decrease in size of the lesions was noted on follow‐up MRI. However, soon after, other lesions were also noted to develop along the adjacent sites. The case presented is proof that PTPR can disseminate to other sites distant from the original lesion. This case was a c‐kit expressing PTPR, which might represent the more primitive nature of this tumor. Ultrastructural examination is useful to differentiate PTPR from other tumors of the pineal gland in addition to immunohistochemistry.     

膀胱小细胞神经内分泌癌临床病理分析

目的探讨膀胱小细胞神经内分泌癌的临床病理特征和生物学行为。方法回顾分析膀胱小细胞神经内分泌癌1例并复习有关文献予以讨论。结果患者中术前未得到明确的病理诊断,术后2周恢复良好,痊愈出院。病理检查:肿瘤细胞表达神经内分泌标记物神经原特异性烯醇酶、嗜铬粒蛋白A和突触素。结论膀胱小细胞神经内分泌癌是一种比较少见的高度恶性肿瘤,有独特的病理形态,早期即可发生转移,预后凶险,活检容易漏诊。     

颅内神经内分泌癌的诊治分析（附15例报道）

目的 探讨颅内神经内分泌癌的临床特征、治疗方法及预后。方法 回顾性分析2013年9月至2018年9月手术治疗的15例颅内神经内分泌癌的临床资料。结果 15例中,单发病灶3例。多发病灶12例。3例单发病灶术中显微镜下全切除,其余12例仅切除引起明显颅内压增高、短期威胁病人生命的病灶;术后病理显示小细胞神经内分泌癌9例,大细胞神经内分泌癌6例。术后仅行放疗8例,同时行放化疗4例,拒绝放化疗1例。术后随访1~12个月,死亡14例,平均生存时间为8个月;1例随访12个月生活基本自理。结论 颅内神经内分泌癌是一类罕见的恶性脑肿瘤,预后差,临床症状和影像学表现缺乏特异性,诊断依靠术后病理学检查,治疗仍然以手术切除为主,辅以放、化疗的综合治疗。     

Isolated pineal region metastasis of small cell lung cancer.

The pineal region is an unusual site for brain metastasis and most metastatic pineal lesions are asymptomatic. Rarely the symptoms of metastatic involvement of the pineal gland precede those of the primary tumor or other metastatic sites. An 83 year-old man presented with gait disturbance and limitation of upward gaze. Brain MRI showed homogeneous enhancement of a solitary mass in the pineal region with obstructive hydrocephalus. A stereotactic biopsy was performed, and small cell carcinoma was diagnosed. A systemic investigation for the primary lesion subsequently revealed small cell carcinoma of the lung. The patient was referred for radiotherapy and chemotherapy. Although rare, metastatic tumor should be considered in the differential diagnosis of pineal region tumors, particularly in elderly patients.     

Pineal metastasis as first clinical manifestation of colorectal adenocarcinoma. Case report.

Cerebral metastases from colorectal adenocarcinomas occur in 8% of the cases. Diagnosis is usually made when primary disease and widespread metastases are already known. We report the case of a patient with single metastases in the pineal region as the first clinical manifestation of a colorectal adenocarcinoma. A 48-year-old female with Parinaud's syndrome for 15 days prior her admission was evaluated in our clinic. She had no symptoms or signs of colorectal disease. MRI examination revealed an heterogeneous lesion with peritumoral gadolinium enhancement, located in the pineal region. The tumor was radically resected through an infratentorial/supracerebellar approach. Histology showed metastatic carcinoma and immunohistochemical examination showed gastrointestinal tract adenocarcinoma. Metastases to the pineal region are extremely rare and should be considered in the differential diagnosis of tumors of this region.     

Lung carcinoma metastasis presenting as a pineal region tumor

An autopsy case is reported of pineal metastasis from lung adenocarcinoma, which is a rare manifestation of the disease. A 75‐year‐old man who had been found to have a lesion in the lung by chest CT 2 years previously, became aware of head heaviness and then suffered consciousness disturbance. Brain MRI revealed a solitary mass in the pineal region with hydrocephalus. At autopsy a midsagittal section of the brain disclosed a well‐circumscribed mass consisting of epithelial cells occupying the third ventricle. Although it should be recognized that such metastasis is very rare, the present case provides further information that might be useful for diagnosis.     

Asymptomatic and symptomatic glial cysts of the pineal gland

Glial cysts of the pineal gland are benign and mostly asymptomatic incidental lesions found in the brain MRI or at autopsy examinations. In rare cases pineal cysts become symptomatic and require surgical intervention. Symptomatic glial cysts may be clinically and radiologically indistinguishable from cystic neoplasms of the pineal region; therefore, histopathological diagnosis is critical for further prognosis and therapy in operated patients. In this paper we present detailed histopathological characteristics of symptomatic glial cysts in 2 surgical cases and of asymptomatic cysts of the pineal gland found at random in 3 autopsy cases. Both surgical patients, a 19-year-old girl and a 17-year-old boy, presented with severe headaches, associated with syncope in one case and insomnia in the second one. Preoperative MR imaging suggested tumour of the pineal gland in case no. 2. Histopathological and immunohistochemical examination of the specimens from both surgical and all autopsy cases revealed a characteristic pattern of cystic structures within the pineal gland, surrounded by layers of a dense fibrillar glial tissue and pineal parenchyma, consistent with non-neoplastic glial cysts. Although histopathological findings in asymptomatic and symptomatic cysts are essentially the same, the cyst in surgical case 1 was unilocular and partly lined with ependymal cells, whereas the cysts in other cases were multilocular, comprising cavities of various size, formed in the central part of gliotic tissue or directly within the pineal parenchyma, and lacked ependymal lining. Possible pathophysiological and clinicopathological significance of some morphological variants of pineal glial cysts is discussed.     

Parinaud syndrome due to solitary pineal metastasis

Parinaud syndrome due to metastatic lesion of the pineal gland has been reported rarely in the literature. We present a case of Parinaud syndrome with solitary pineal metastasis of an oat cell carcinoma.     

Bcl‐2 expression in a papillary tumor of the pineal region

Neuroepithelial papillary tumor of the pineal region (PTPR) has been described by several groups and recognized by the 2007 World Health Organization Classification of Tumors of the Central Nervous System. The proto‐oncogen Blc‐2 can function as an apoptosis suppressor and can promote neoplastic transformation. It may also be involved in neuroendocrine differentiation in some tumors. As PTPRs express neuroendocrine markers, we investigated the expression of Bcl‐2 in tumoral cells of a new case of PTPR in a 42‐year‐old woman. Bcl‐2 immunostaining was detected in the cytoplasm of the tumoral cells; staining intensity was heterogeneous from cell to cell and more intense in papillary areas. This intense expression of Bcl‐2 in one case of PTPR with a high proliferation index (8%) might be related to the malignancy of this neoplasm. It will be interesting to investigate the prognosis impact of Bcl‐2 expression in a large series of PTPRs.     

Malignant solitary fibrous tumor arising from the pineal region: case study and literature review

We report a case of malignant solitary fibrous tumor involving the pineal region in a 49‐year‐old woman. The patient presented with headache, slowly progressive weakness of the right lower extremities and upgaze palsy over the past year. Histologically, the tumor was composed of moderately hypercellular proliferated spindle cells with eosinophilic collagen bands. These cells were diffusely and strongly immunoreactive with CD34, CD99, and vimentin, but were negative with epithelial membrane antigen, S‐100 protein, Bcl‐2, smooth muscle actin, cytokeratin and glial fibrillary antigenic protein. MIB‐1 labeling indices and mitosis rates were 7.3 ± 1.8% and 5 per 10 high power fields, respectively. Ultrastructural examination revealed that the neoplastic cells had features of fibroblastic differentiation. Differential diagnoses included fibrous meningioma and hemangiopericytoma. The present case provides one unique example of a rare entity to the already diverse spectrum of the pineal region neoplasms encountered in neuropathology.     

Fibro‐osseous lesion of the pineal region resembling osteoblastoma: A case report

A case of unusual fibro‐osseous lesion resembling osteoblastoma of the pineal region is reported, in a 50‐year‐old man. The patient presented with a history of headache, vomiting and generalized tonic‐clonic seizures. CT scan showed a hyperdense lesion in the posterior third ventricle with obstructive hydrocephalus. On histopathology the lesion showed cellular areas with oval to polygonal cells showing clear to eosinophilic cytoplasm along with focal anastomosing network of osetoid‐like extracellular material lined by similar cells. The extracellular material was seen densely calcified at places with cement lines and Haversian canal formation. The cells were strongly immunoreactive for epithelial membrane antigen and focally for S‐100 protein and negative for glial fibrillary acidic protein.     

松果体区中间型滋养细胞肿瘤临床病理学特征

目的探讨松果体区中间型滋养细胞肿瘤的临床病理学特征。方法回顾分析一例松果体区中间型滋养细胞肿瘤患儿的临床诊断与治疗经过,并对手术切除标本进行HE和免疫组织化学染色,于光学显微镜下观察组织学形态和肿瘤标志物表达变化。结果患儿为6岁男孩,临床表现为阴茎增大并生长迅速;MRI检查显示松果体区占位性病变,临床拟诊为生殖细胞瘤。经实验性放射治疗无效后施行外科手术切除。光学显微镜观察肿瘤组织呈大片状坏死,伴大范围钙化和散在新鲜出血,可见实片状、上皮样生长的单核异型性细胞,细胞间相对一致,部分肿瘤细胞围绕血管壁生长并浸润血管壁,细胞质嗜酸性或透明,细胞核呈圆形或不规则形,部分肿瘤细胞核内可见假包涵体,核分裂象罕见;肿瘤细胞高表达广谱细胞角蛋白、CAM5.2、人胎盘催乳素、八聚体结合转录因子3/4、表皮生长因子受体和上皮型钙黏附蛋白;散在表达P53,Ki67抗原标记指数约为10%;极少数肿瘤细胞表达人绒毛膜促性腺激素β亚单位;不表达胎盘碱性磷酸酶、甲胎蛋白、CD30(Ki1)和P63。结论松果体区中间型滋养细胞肿瘤临床罕见,其组织形态学具有部分胎盘部位滋养细胞肿瘤和部分上皮样滋养细胞肿瘤的特点。治疗原则为放射治疗、手术切除辅助药物化疗。     

Pineal chordoid meningioma complicated by repetitive hemorrhage during pregnancy: Case report and literature review

Chordoid meningioma is an uncommon variant of meningioma, and is very rarely found in the pineal region. We report a case of pineal region chordoid meningioma occurring in a young woman complicated by repetitive hemorrhages in the setting of pregnancy. A 23‐year‐old woman, 28 weeks pregnant, was transferred to our hospital for further management of a multi‐septated, hemorrhagic pineal region mass and hydrocephalus. MRI revealed a heterogeneous T2‐hyperintense lesion measuring 1.7 × 1.7 cm in the pineal gland. Resection of the tumor through an occipital transtentorial approach was performed. Histopathologic examination of the lesion confirmed the diagnosis of chordoid meningioma demonstrating cords and clusters of eosinophilic cells with rare cytoplasmic vacuolation arranged in a mucinous stroma. Additionally, there was abundant lymphoplasmacytic infiltration within the tumor. The details of this case are presented with a review of the literature.     

Pineal parenchymal tumor of intermediate differentiation with cytologic pleomorphism

We report a case of pineal parenchymal tumor in a 33‐year‐old man incidentally detected by radiological examination. The MRI showed an unhomogeneously enhanced, small tumor (approximately 1 cm in size) in the pineal region. A tumor specimen was obtained at endoscopic biopsy. Routine histology showed a highly cellular tumor characterized by a predominance of small cells showing high nuclear : cytoplasmic ratio and moderate nuclear atypia, pleomorphism including giant cells and an absence of pineocytomatous rosettes. Mitotic figures were rare (approximately 1 per 10 high‐power fields). Tumor necrosis was not evident. Immunohistochemically, the neoplastic cells showed positivity for neural markers (neurofilament protein, synaptophysin) and pinealocyte‐associated antibodies (PP1, PP5, PP6), but not for glial fibrillary acidic protein or S‐100. The MIB‐1 labeling index was relatively high (6.3%). Ultrastructurally, there was some evidence of pinealocytic differentiation, such as vesicle‐crowned rodlets (synaptic ribbons) and paired twisted filaments in neoplastic cells. Thus, the tumor was confirmed as a pineal parenchymal tumor of intermediate differentiation by histology, immunohistochemistry and electron microscopy. This case indicates that marked cytologic pleomorphism can occur in pineal parenchymal tumors of intermediate differentiation.     

Immunohistochemical characterization of pineal parenchymal tumors using novel monoclonal antibodies to the pineal body

To characterize the immunohistochemical nature of pineal parenchymal tumors (PPT), we examined nine cases of normal pineal bodies and 23 cases of PPT using several neuronal and glial antibodies and 10 novel monoclonal antibodies raised against human pineal tissue. The PPT were classified into four pineocytoma, five pineal parenchymal tumor of intermediate differentiation (Int‐PPT), and 14 pineoblastoma. The pinealocytes, parenchymal cells of the pineal body, were labeled with five neuronal and seven pineal monoclonal (from PP1 to PP7) antibodies in the normal pineal bodies. The subjects ranged from 3 to 85 years old, 12 female and eight male subjects were studied. Antibodies to glial cells PI1, PI2 and PX1, stained interstitial cells of the pineal body. Many of the PPT showed positive immunostaining for pinealocyte‐associated antigens and neuronal markers. The intensity of immunostaining showed some association with the degree of differentiation of the tumor, but there was a considerable variety of staining from case to case. The pineocytomas are more immunopositive than are the Int‐PPT or pineoblastoma for neuronal and pinealocyte‐associated antibodies. In particular the neurofilament protein (NFP)68 kDa, PP1 and PP6 showed significant differences of reactivity between pineocytoma, Int‐PPT and pineoblastoma, when compared in groups showing extensive positive staining (positive staining in almost all areas of the tumor). By using three representative antibodies, anti‐NFP68kDa, PP1 and PP6, we were able to make a clear distinction between pineoblastoma, Int‐PPT and pineocytoma. Glial fibrillary acidic protein (GFAP), PI1 and PI2 antibodies only occasionally showed a small number of positive cells in the tumor, and thus we considered these cells to be non‐neoplastic interstitial cells or reactive astrocytes entrapped in the tumor. Our data suggest that the glial differentiation of PPT may occur, but that it seems to be a very rare event.