Pineocytoma with malignant transformation to pineal parenchymal tumor with intermediate differentiation and leptomeningeal dissemination after subtotal tumor resection and adjuvant radiotherapy

Ann-Shung Lieu; Chun-Chieh Wu; Chee-Yin Chai; Yu-Chun Ma; Hui-Yuan Su

doi:10.4103/ijpm.ijpm_817_21

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Year : 2023 | Volume : 66 | Issue : 1 | Page : 141-144

Pineocytoma with malignant transformation to pineal parenchymal tumor with intermediate differentiation and leptomeningeal dissemination after subtotal tumor resection and adjuvant radiotherapy

Ann-Shung Lieu¹, Chun-Chieh Wu², Chee-Yin Chai³, Yu-Chun Ma², Hui-Yuan Su⁴
¹ Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University; Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
² Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
³ Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University; Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University; Department of Pathology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University; Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
⁴ Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University; Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

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Date of Submission	12-Aug-2021
Date of Decision	14-Aug-2021
Date of Acceptance	14-Aug-2021
Date of Web Publication	28-Nov-2022

Abstract

Pineocytoma is a rare tumor. It is rare for pineocytoma to present as leptomeningeal metastasis. We present a rare case of pineocytoma with malignant transformation and leptomeningeal metastasis after subtotal tumor resection and adjuvant radiotherapy. This case was a 58-year-old male with an unsteady gait for 2 months. Enhanced brain magnetic resonance imaging revealed a heterogeneous mass involving the pineal region. The initial pathological diagnosis of pineocytoma was confirmed after subtotal tumor resection. Two years after adjuvant radiotherapy to the primary site, the magnetic resonance imaging showed C2 and T2 metastatic lesions, with the final pathological diagnosis being pineal parenchymal tumor (PPT) with intermediate differentiation after the removal of T2 intramedullary tumor. After that adjuvant radiotherapy at the cervical and thoracic spinal cord was completed. There was no recurrence of the tumor 1 year after the radiotherapy. We report a rare case of pineocytoma with malignant transformation to PPT with intermediate differentiation and leptomeningeal dissemination.

Keywords: Leptomeningeal dissemination, malignant transformation, pineal parenchymal tumor with intermediate differentiation, pineocytoma, radiotherapy

How to cite this article:
Lieu AS, Wu CC, Chai CY, Ma YC, Su HY. Pineocytoma with malignant transformation to pineal parenchymal tumor with intermediate differentiation and leptomeningeal dissemination after subtotal tumor resection and adjuvant radiotherapy. Indian J Pathol Microbiol 2023;66:141-4

How to cite this URL:
Lieu AS, Wu CC, Chai CY, Ma YC, Su HY. Pineocytoma with malignant transformation to pineal parenchymal tumor with intermediate differentiation and leptomeningeal dissemination after subtotal tumor resection and adjuvant radiotherapy. Indian J Pathol Microbiol [serial online] 2023 [cited 2023 May 27];66:141-4. Available from: https://www.ijpmonline.org/text.asp?2023/66/1/141/362060

Introduction

Pineal parenchymal tumors (PPTs) are very rare, accounting for less than 0.3% of the intracranial tumors.^[1] They are classified into three classes, including WHO grade I (pineocytoma), WHO grades II and III (pineal parenchymal tumor with intermediate differentiation, PPTID), and WHO grade IV (pineoblastoma).^[2],[3] PPTID shows morphological features intermediate between pineocytoma and pineoblastoma. Due to limited information, there is no standard protocol for the treatment of PPTID.^[4] Due to frequent local recurrence, adjuvant radiotherapy or chemotherapy or a combination of both is suggested to optimize the local control rate.^[5] We present a rare case of pineocytoma with malignant transformation and leptomeningeal metastasis.

Case History

A 58-year-old man presented with an unsteady gait for 2 months. Poor short-term memory and lethargy were also noted over the previous half-year. No double vision, slurred speech, limb weakness, urinary incontinence, fever, or bodyweight loss were indicated. The brain computed tomography for a head injury after falling due to an unsteady gait demonstrated a pineal region tumor with size 3.8 cm and obstructive hydrocephalus, while an enhanced brain magnetic resonance image (MRI) revealed a heterogeneous tumor mass with size 2.7 cm involving the pineal gland and the bilateral hypothalamus, leading to obstructive hydrocephalus [Figure 1]a, [Figure 1]b, [Figure 1]c.

Figure 1: Magnetic resonance image finding of the brain. (a) There is a heterogeneous tumor mass involving the pineal gland and the bilateral hypothalamus. This irregularly shaped tumor is iso- to hypointense to the cortex on the T2-weighted image. (b) An iso- to hypointense tumor with size 2.7 cm is demonstrated on the T2-fluid-attenuated inversion recovery image. (c) Besides, heterogeneous enhancement of the tumor is also noted on the T1-weighted image with the enhancement of gadolinium. (d) The prior heterogeneous tumor mass involving the pineal gland and the bilateral hypothalamus is not depicted and without any imaging evidence showing regional heterogeneous enhancement. There is no regional recurrence 12 months after surgical removal of tumor and radiotherapy

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Through the right-side occipital craniotomy and a supra-tentorial and trans-tentorial approach, a grayish-colored, fragile, and readily-bleeding-after-contact pineal tumor was noted. Subtotal removal of the pineal tumor was performed, and then, an extra-ventricular drainage tube was kept in position. Due to persistent hydrocephalus, a ventriculoperitoneal shunt was performed on the third week after the operation.

After the operation, he had regular follow-up at our outpatient department. Underdiagnosis of residual pineocytoma, regional radiotherapy for the brain 5040 cGy in 28 fractions was completed within 1 month, and subsequent brain MRI disclosed no local recurrence and leptomeningeal enhancement [Figure 1]d. Two years after the radiotherapy, suspected spinal metastasis on the C2 spinal cord was demonstrated on brain MRI. Due to progressive numbness over bilateral distal fingers, a cervical spine MRI was arranged, disclosing metastasis at the levels of C2 and T2 spinal areas [Figure 2]a and [Figure 2]b. Further surgical intervention was suggested.

Figure 2: Magnetic resonance image finding of the cervical and thoracic spine. (a) There are hyperintense intramedullary lesions in the C2 and T2 spinal cord on the T2-weighted image. (b) There are hypervascular and intramedullary lesions in C2 and T2 levels of the spinal cord on the T1-weighted image with the enhancement of gadolinium. Thickening and some plaque along the brain stem, cervical, and thoracic spinal sections are noted. The imaging study also demonstrates suspected leptomeningeal carcinomatosis along the brain stem, cervical, and thoracic spine. (c) After surgical removal of T2 spinal cord lesion and post-operation regional radiotherapy, there are no residual lesions in the brainstem, C2 and T2 spinal cord on the T2-weighted image. There are hyperintense signals in the T2 spinal cord that are suspected of demyelination change after tumor removal on the T2-weighted image. (d) No lesion with contrast enhancement is found nor leptomeningeal enhancement on T1-weighted image with the enhancement of gadolinium 1 year after completing radiotherapy

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In the third surgery, the operation of T2 and T3 laminectomy, durotomy, and opening the arachnoid membrane were performed, with a grayish tumor found at the surface of the T2 spinal cord; then, removal of the intradural and intramedullary tumors was performed. After that radiotherapy 4680 cGy in 27 fractions at C2 and T2 spinal cord areas was completed in the subsequent 2 weeks under pathological diagnosis of PPTID with leptomeningeal dissemination. No recurrence of the tumor was noted on MRI 1 year after completing radiotherapy [Figure 2]c, [Figure 2]d.

The pathological sections showed a hypercellular tumor composed of relatively small, uniform, and mature cells arranged in a sheet-like pattern. Th mitotic figures were few. Immunohistochemical staining disclosed neuron-specific enolase (+), synaptophysin (+), D99(-), and Ki-67 labeling index of 1%. Based on the morphology and immunohistochemical studies, the features were compatible with pineocytoma [Figure 3]. From the third surgery, the tumor showed moderate to high cellularity composed of neoplastic cells harboring round the nuclei with mild-to-moderate atypia, and salt-and-pepper chromatin. The neoplastic cells were positive for synaptophysin, chromogranin A, and negative for cytokeratin (AE1/AE3), with the glial fibrillary acidic protein and S100 proteins expressed in astrocytic interstitial cells. The mitotic figures were 3 per 10 high-powered fields, while the Ki-67 labeling index was around 20%. Taken together with the morphology and immunohistochemical studies, this was consistent with PPTID [Figure 4].

Figure 3: Histological and immunohistochemical observations of the pineal region tumor. (a) Pathology sections of Hematoxylin and Eosin stain show a hypercellular tumor composed of relatively small, uniform, and mature cells arranged in a sheet-like pattern. Besides, the mitotic figures are few. (b–d) The immunohistochemical staining discloses neuron-specific enolase (+) (b), synaptophysin (+) (c) and Ki-67 labeling index 1% (d). Based on the morphology and immunohistochemical studies, the features are compatible with pineocytoma

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Figure 4: Histological and immunohistochemical observations of the T2 spinal cord tumor. (a) Pathology sections of Hematoxylin and Eosin stain show moderate to high cellularity composed of neoplastic cells harboring round nuclei with mild-to-moderate atypia, and salt-and-pepper chromatin. (b–d) The immunohistochemical staining discloses that the neoplastic cells are positive for synaptophysin (b). (c) Glial fibrillary acidic proteins are expressed in astrocytic interstitial cells. (d) The Ki-67 labeling index is around 20%. Together with morphology and immunohistochemical studies, it is consistent with pineal parenchymal tumor with intermediate differentiation

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Discussion

The most important clinical signs of pineal region lesions are non-specific intracranial hypertension syndrome (47%), headache (13%), diplopia (10%), papillary edema (8%), Parinaud's syndrome (7%), cerebellar syndrome (5%), and ataxia (2%).^[6] The initial chief complaint of our case is an unsteady gait for 2 months. The image study presents solid masses at the pineal region on preoperative MRI. It is important to make differential diagnoses among pure germinomas, non-germinomatous germ-cell tumors, primary pineal neoplasms, high-grade gliomas, and lymphomas in a pineal solid mass. Pure germinoma might appear as having a typical butterfly-shaped image on contrast-enhanced MRI axial cuts.^[7] Non-germinomatous tumors include yolk-sac tumors, embryonal carcinomas, and choriocarcinomas. These tumors are not easily differentiated using MRI or computed tomography, and the images of PPTID are non-specific while sharing the same characteristics of pineocytomas. A lesion greater than 3 cm in diameter, which is associated with hemorrhage, necrosis, and cerebrospinal fluid dissemination, is typical for pineoblastoma. The magnetic resonance spectrum imaging might play a role in helping to differentiate the germ-cell tumors from other tumors, as the germ-cell tumors tend to have increased lipid/creatinine ratios. The astrocytic gliomas might have diffused growth patterns, and in high-grade gliomas, moderate to heterogeneous enhancement is common, while glioblastomas typically have necrotic lesions.^[7]

Primary intracranial tumors of the pineal region have been reported to make up about 0.5% of all intracranial neoplasms.^[8] These tumors can be categorized into germinal tumors (30–50%), PPTs (14–30%), and glial and other tumors from the supporting stroma (25%).^[9] The radical removal of the pineal tumor is the ideal goal when considering prognosis, including those for non-germinomatous germ-cell tumors, teratomas, and PPTs.^[10] In addition, tectal gliomas might coexist with fragments of a pineal cyst; therefore, some misdiagnosis might occur due to the similarities between pineal cysts, pineal astrocytomas, and pineocytomas in histological evaluations and can occur when insufficient or inappropriate specimens are collected.^[11]

Pineocytomas are characterized by small, uniform, and mature cells with a well-differentiated pattern. Besides, they might present a large number of pineocytomatous rosettes lacking mitoses. Pineoblastomas are tumors composed of highly cellular contents characterized by irregular nuclei, high nucleus to cytoplasm ratio, high mitoses, and patternless sheets with necrosis. PPTIDs are defined as an intermediate stage between pineocytoma and pineoblastoma. There is no necrosis and endothelial proliferation in the PPTIDs. On the other hand, PPTIDs present positive the immunohistochemical results of synaptophysin, chromogranin A, neurofilament, and renal S antigen. Besides, the proliferation index MIB-1 is between 3 and 10%.^[1] Although the proliferative index (MIB-1 Ki-67 labeling index) is up to 20%, there is no necrosis and endothelial proliferation in our case. The pathology diagnosis is PPTID rather than pineoblastoma.

In this case, there was no local recurrence after surgery and adjuvant radiotherapy. Pineocytoma with leptomeningeal dissemination is rare, and to our knowledge, this is only the third case of pineocytoma with malignant transformation and leptomeningeal dissemination presented after a review of the literature.^[1],[12] Due to limited information, optimal management after subtotal resection of pineocytoma is not determined, although radiotherapy for residual pineocytoma and PPTID might be effective on the local control of the tumor. Cranio-spinal irradiation is suggested for pineoblastoma and PPTID with spinal dissemination.^[10] Adjuvant spinal irradiation was not necessary in our case owing to the lack of evidence of spinal cord involvement when the patient was diagnosed with pineocytoma initially. Unfortunately, the MRI disclosed spinal dissemination with the involvement of the cervical and thoracic spinal cord 2 years after the local radiotherapy for the pineal region. In addition to spinal dissemination, malignant transformation to PPTID was also proven after the removal of the spinal cord tumor. For adjuvant treatment, radiotherapy 4680 cGy in 27 fractions for spinal metastasis was arranged.

Considering local tumor control for pineocytoma, the gross total resection of the tumor represents better 1- and 5-year progression-free survival rates and overall survival rates than that in the patients receiving subtotal tumor resection and adjuvant radiotherapy.^[13] There is no definite role of adjuvant radiotherapy for residual pineocytoma when gross total resection is not possible.^[14] However, craniospinal irradiation should be considered after leptomeningeal spreading in patients with the diagnosis of PPTID.^[5] Due to less evidence, there is no definite protocol for the treatment of pineocytoma with malignant transformation to the PPT with intermediate differentiation and leptomeningeal dissemination.

Conclusion

We report a rare case of pineocytoma with malignant transformation and leptomeningeal seeding to the cervical and thoracic cord 2 years after the partial removal of the PPT and adjuvant radiotherapy. Leptomeningeal dissemination of the pineal parenchymal tumor with the malignant transformation from pineocytoma to PPTID was confirmed by pathology after the removal of the tumor in the thoracic cord. Although local radiotherapy for pineocytoma after subtotal resection, leptomeningeal dissemination still occurred after a moderate period of follow-up. The efficacy of spinal radiotherapy for leptomeningeal dissemination was good in this case. This is the third case of pineocytoma with malignant transformation and leptomeningeal dissemination after surgical removal and radiotherapy. Even though spinal seeding is less likely, persistent follow-up after surgery and radiotherapy is very important for patients with the diagnosis of pineocytoma.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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