Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 -- 1175 2024-02-26 11:17:25 |
2 layout Meta information modification 1175 2024-02-27 03:03:20 |

Video Upload Options

Do you have a full video?

Confirm

Are you sure to Delete?
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Bianconi, A.; Panico, F.; Lo Zito, B.; Do Trinh, A.; Cassoni, P.; Ricardi, U.; Garbossa, D.; Cofano, F.; Mantovani, C.; Bertero, L. Pathological Features of Pineal Parenchymal Tumors. Encyclopedia. Available online: https://encyclopedia.pub/entry/55451 (accessed on 16 April 2024).
Bianconi A, Panico F, Lo Zito B, Do Trinh A, Cassoni P, Ricardi U, et al. Pathological Features of Pineal Parenchymal Tumors. Encyclopedia. Available at: https://encyclopedia.pub/entry/55451. Accessed April 16, 2024.
Bianconi, Andrea, Flavio Panico, Bruna Lo Zito, Andrea Do Trinh, Paola Cassoni, Umberto Ricardi, Diego Garbossa, Fabio Cofano, Cristina Mantovani, Luca Bertero. "Pathological Features of Pineal Parenchymal Tumors" Encyclopedia, https://encyclopedia.pub/entry/55451 (accessed April 16, 2024).
Bianconi, A., Panico, F., Lo Zito, B., Do Trinh, A., Cassoni, P., Ricardi, U., Garbossa, D., Cofano, F., Mantovani, C., & Bertero, L. (2024, February 26). Pathological Features of Pineal Parenchymal Tumors. In Encyclopedia. https://encyclopedia.pub/entry/55451
Bianconi, Andrea, et al. "Pathological Features of Pineal Parenchymal Tumors." Encyclopedia. Web. 26 February, 2024.
Pathological Features of Pineal Parenchymal Tumors
Edit

Pineal parenchymal cell tumors (PPT) are a rare group of tumors representing less than 1% of all primary central nervous system neoplasms. Originating from pineocytes or their precursor cells, these tumors pose unique challenges both during the diagnostic assessment and clinical management. 

pineal region pineal parenchymal tumor pineal gland biopsy intensity modulation radiation therapy

1. Introduction

Pineal parenchymal cell tumors (PPT) are a rare group of tumors representing less than 1% of all primary central nervous system neoplasms. Originating from pineocytes or their precursor cells, these tumors pose unique challenges both during the diagnostic assessment and clinical management. The World Health Organization (WHO) classification stratifies PPTs into distinct entities, ranging from the well-differentiated pineocytomas to the highly malignant pineoblastomas [1]. Among them, the intermediate category of pineal parenchymal cell tumors of intermediate differentiation (PPTID) remains a critically debated subset, presenting a spectrum of histologic features that defy easy categorization [2].
Tackling the management of these tumors remains a complex endeavor, primarily due to their rarity and the resulting limited pool of comprehensive studies. The inherent clinical heterogeneity exhibited by PPTs adds an additional layer of complexity.

2. Pathological Features of Pineal Parenchymal Tumors

According to the latest 2021 WHO classification of central nervous systems, two entities are defined at the opposite ends of the spectrum of pineal parenchyma tumors: pineocytoma (PC), a well-differentiated neoplasm, and pineoblastoma (PB), a poorly differentiated, aggressive neoplasm [1]. The pineal tumor of intermediate differentiation (PPTID) is located in the middle, representing a less defined group of neoplasms [3][4].

2.1. Pineocytomas

Pineocytoma was defined by the WHO in 2021 as a Grade 1 entity—a well-differentiated pineal parenchymal neoplasm exhibiting expansile growth that can result in compression of adjacent structures, leading to variable signs and symptoms [5]. The cut surface shows a well-circumscribed homogeneous or granular mass with a greyish-tan appearance. Histologically, it presents as a moderately cellular neoplasm composed of small, round, blue, and mature cells organized in sheets or showing large pineocytomatous rosettes, a hallmark feature, not present in the normal pineal gland. Gangliocytic differentiation can be variably present and a pleomorphic variant has also been described [6].
Mitotic figures are rarely present in pineocytomas [7][8][9]. The mean Ki67, in most cases, is <1% [9][10][11]. Pineocytomas exhibit strong positivity for synaptophysin, neuron-specific enolase, and NFP [2][7][11][12][13][14]. Other markers have shown variable positivity, including class III beta-tubulin, microtubule-associated protein tau, and chromogranin-A [2][7][12][13]. On average, the interval between the onset of symptoms and surgery was four years for pineocytomas [3]. To date, there have been no reported cases of metastasis in patients affected by pineocytoma [6][15]. The five-year survival in this group ranges from 86% to 91% [6][15]. A review highlighted that the extent of surgical resection is the main independent prognostic factor [16]. Immunoexpression of CRX, a transcription factor, and ASMT, a fundamental enzyme in the synthesis of melatonin, serves as a sign of a biological link to pinealocytes [17][18][19]. There are no recurrent genetic mutations in pineocytomas [20][21], but they exhibit a distinct methylation profile [22].

2.2. Pineal Parenchymal Tumors of Intermediate Differentiation

Pineal tumors of intermediate differentiation are characterized by intermediate malignancy between pineocytoma and pineoblastoma [5][23]. Histologically, they are composed of diffuse sheets or large lobules of monomorphic round cells that appear more differentiated than those observed in pineoblastomas. They can show two main microscopic patterns: they can be densely lobulated with an endocrine-arranged vascularity or diffuse, mimicking oligodendroglioma or neurocytoma. The nuclei are round with moderate atypia and “salt and pepper” chromatin [6][24]. According to the WHO in 2021, Grade 2 or 3 can be assigned based on histopathological features, highlighting the intrinsic heterogeneity of this neoplasm [1].
PPTIDs are positive for synaptophysin [7][11][25], while showing variable positivity for NFP and chromogranin-A [2][7][14][26]. As in pineocytoma, CRX is expressed as well as ASMT/HIOMT, which acts as both a diagnostic and prognostic marker [17][18][19]. Mitotic activity ranges from low to moderate [5]. The mean proliferation index Ki67 is significantly different from pineocytomas and pineoblastomas, with values ranging from 3.5% to 16.1% [20][25][27][28]. PPTIDs are less aggressive neoplasms compared to pineoblastoma, with a higher probability of localized disease at diagnosis. A more favorable prognostic difference between these entities can be observed by comparing the median overall survival of PPTID against PB (165 months vs. 77 months) and progression-free survival (93 months vs. 46 months) [29]. Jouvet et al. and Fauchon et al. have proposed a prognosis-oriented classification of PPTIDs with mitotic count and neuronal differentiation assessed by anti-NFP immunohistochemistry [7][15]. Low-grade PPTID, corresponding to WHO grade 2, was defined as having <6 mitosis per 10 HPF and expression of NFP in many cells [7]. Five-year survival in this group was 74%, and relapse occurred in 26%, mostly in the first site of the neoplasm after some delay [15]. High-grade PPTID, corresponding to WHO grade 3, was defined as having <6 mitosis without NFP expression by immunohistochemistry or >6 mitosis with NFP expression. Five-year survival in this group was 39%, and relapse occurred in 53%, mostly outside the pineal region [7][15]. Low-grade and high-grade prognostic groups showed a difference in the Ki67 proliferation index (5.2% vs. 11.2%) [8]. Nevertheless, the latest WHO classification of CNS tumors acknowledges that definite histological grading criteria are still missing.
It has been demonstrated that PPTIDs can harbor KBTBD4 small in-frame insertions [30]. The copy-number profile of PPTIDs is relatively flat, with some cases of broad gains or losses, particularly chromosome imbalances resembling those observed in pineoblastomas, though minor [20][22]. PPTIDs have a distinct methylation profile that can be further distinguished into two subtypes whose prognosis is still to be established: PPTID-A and PPTID-B [22].

2.3. Pinealoblastomas

Pineoblastoma is a malignant Grade 4 neoplasm—a poorly differentiated, highly cellular, malignant embryonal neoplasm arising in the pineal gland. Upon gross examination, they appear as partially defined invasive masses—soft and friable, pinkish-grey. Pineoblastomas appear as small round blue tumors composed of highly cellular sheets of small cells without a defined pattern. They show irregular, hyperchromatic nuclei with an occasional small nucleolus, high nuclear-to-cytoplasmic ratio, scant cytoplasm, and faint cell borders [5][24].
Pinealoblastomas exhibit positivity for synaptophysin and NSE [7]. Staining positivity for NFP and chromogranin A is significantly less frequent compared to pineocytomas [7][14][31]. There is no loss of SMARCB1/INI1 staining in pineoblastomas, a useful feature to distinguish them from atypical teratoid rhabdoid tumors [32]. Pineoblastoma is a neoplasm characterized by a high mean proliferation index, ranging from 16.9% to 50.1% [8][11][19][20]. It stands out as the most aggressive neoplasm of the pineal region, with frequent craniospinal dissemination and extracranial metastasis [15][24][33][34]. In older series, overall survival in pineoblastoma was reported to be as low as 1.3 years; however, recent studies indicate a better median overall survival time, reaching 4.1–8.7 years [35][36]. Negative prognostic predictors for pineoblastoma include disseminated disease at diagnosis, young age, and partial surgical resection [37]. The prognosis of pineoblastoma is extremely unfavorable, with patients often succumbing within two years from diagnosis [3].
From a cytogenetic perspective, structural alterations of chromosome 1 have been observed, and there may be losses of chromosomes [2][4][5][12][15] with some rare focal gains [20][38][39]. Reports also mention copy number variations and/or mutually exclusive mutations of DICER1, DROSHA, and DGCR8 [22][40][41][42][43]. DNA methylation profiling has identified four subgroups of pineoblastomas: miRNA processing altered type 1, miRNA processing altered type 2, RB1 altered, and MYC/FOXR activated [22][41][43]. These subgroups carry prognostic implications, with the miRNA processing altered type 2 subtype showing an overall good prognosis, while the outcomes of RB1-altered and the MYC/FOXR2-activated subgroups are notably poor.

References

  1. Louis, D.N.; Perry, A.; Wesseling, P.; Brat, D.J.; Cree, I.A.; Figarella-Branger, D.; Hawkins, C.; Ng, H.K.; Pfister, S.M.; Reifenberger, G.; et al. The 2021 WHO Classification of Tumors of the Central Nervous System: A summary. Neuro-Oncology 2021, 23, 1231–1251.
  2. Jouvet, A.; Derrington, E.; Pialat, J.; Lapras, C.; Fèvre-Montange, M.; Besançon, R.; Belin, M.F.; Saint-Pierre, G. Structural and ultrastructural characteristics of human pineal gland, and pineal parenchymal tumors. Acta Neuropathol. 1994, 88, 334–348.
  3. Borit, A.; Blackwood, W.; Mair, W.G.P. The Separation of Pineocytoma from Pineoblastoma. Cancer 1980, 45, 1408–1418.
  4. Scheithauer, B.W. Pathobiology of the pineal gland with emphasis on parenchymal tumors. Brain Tumor Pathol. 1999, 16, 1–9.
  5. Chiechi, M.V.; Smirniotopoulos, J.G.; Mena, H. Pineal Parenchymal Tumors. J. Comput. Assist. Tomogr. 1995, 19, 509–517.
  6. Schild, S.E.; Scheithauer, B.W.; Haddock, M.G.; Wong, W.W.; Lyons, M.K.; Marks, L.B.; Norman, M.G.; Burger, P.C. Histologically confirmed pineal tumors and other germ cell tumors of the brain. Cancer 1996, 78, 2564–2571.
  7. Jouvet, A.; Saint-Pierre, G.; Fauchon, F.; Privat, K.; Bouffet, E.; Ruchoux, M.; Chauveinc, L.; Fèvre-Montange, M. Pineal Parenchymal Tumors: A Correlation of Histological Features with Prognosis in 66 Cases. Brain Pathol. 2000, 10, 49–60.
  8. Fèvre-Montange, M.; Szathmari, A.; Champier, J.; Mokhtari, K.; Chrétien, F.; Coulon, A.; Figarella-Branger, D.; Polivka, M.; Varlet, P.; Uro-Coste, E.; et al. Pineocytoma and Pineal Parenchymal Tumors of Intermediate Differentiation Presenting Cytologic Pleomorphism: A Multicenter Study. Brain Pathol. 2008, 18, 354–359.
  9. Kanno, H.; Nishihara, H.; Oikawa, M.; Ozaki, Y.; Murata, J.; Sawamura, Y.; Kato, M.; Kubota, K.; Tanino, M.; Kimura, T.; et al. Expression of O6-methylguanine DNA methyltransferase (MGMT) and immunohistochemical analysis of 12 pineal parenchymal tumors. Neuropathology 2012, 32, 647–653.
  10. Fauchon, F. Utility of Ki67 immunostaining in the grading of pineal parenchymal tumours: A multicentre study. Neuropathol. Appl. Neurobiol. 2012, 38, 87–94.
  11. Arivazhagan, A.; Anandh, B.; Santosh, V.; Chandramouli, B. Pineal parenchymal tumors—Utility of immunohistochemical markers in prognostication. Clin. Neuropathol. 2008, 27, 325–333.
  12. Kuchelmeister, K.; Gullotta, F.; von Borcke, I.M.; Klein, H.; Bergmann, M. Pleomorphic pineocytoma with extensive neuronal differentiation: Report of two cases. Acta Neuropathol. 1994, 88, 448–453.
  13. Numoto, R.T. Pineal parenchymal tumors: Cell differentiation and prognosis. J. Cancer Res. Clin. Oncol. 1994, 120, 683–690.
  14. Yamane, Y.; Mena, H.; Nakazato, Y. Immunohistochemical characterization of pineal parenchymal tumors using novel monoclonal antibodies to the pineal body. Neuropathology 2002, 22, 66–76.
  15. Fauchon, F.; Jouvet, A.; Paquis, P.; Saint-Pierre, G.; Mottolese, C.; Ben Hassel, M.; Chauveinc, L.; Sichez, J.-P.; Philippon, J.; Schlienger, M.; et al. Parenchymal pineal tumors: A clinicopathological study of 76 cases. Endocrine 2000, 46, 959–968.
  16. Clark, A.J.; Sughrue, M.E.; Ivan, M.E.; Aranda, D.; Rutkowski, M.J.; Kane, A.J.; Chang, S.; Parsa, A.T. Factors influencing overall survival rates for patients with pineocytoma. J. Neuro-Oncol. 2010, 100, 255–260.
  17. Santagata, S.; Maire, C.L.; Idbaih, A.; Geffers, L.; Correll, M.; Holton, K.; Quackenbush, J.; Ligon, K.L. CRX Is a Diagnostic Marker of Retinal and Pineal Lineage Tumors. PLoS ONE 2009, 4, e7932.
  18. Manila, A.; Mariangela, N.; Libero, L.; Francesca, G.; Romana, B.F.; Felice, G. Is CRX Protein a Useful Marker in Differential Diagnosis of Tumors of the Pineal Region? Pediatr. Dev. Pathol. 2014, 17, 85–88.
  19. Fukuda, T.; Akiyama, N.; Ikegami, M.; Takahashi, H.; Sasaki, A.; Oka, H.; Komori, T.; Tanaka, Y.; Nakazato, Y.; Akimoto, J.; et al. Expression of Hydroxyindole-O-Methyltransferase Enzyme in the Human Central Nervous System and in Pineal Parenchymal Cell Tumors. J. Neuropathol. Exp. Neurol. 2010, 69, 498–510.
  20. Rickert, C.H.; Simon, R.; Bergmann, M.; Dockhorn-Dworniczak, B.; Paulus, W. Comparative genomic hybridization in pineal germ cell tumors. J. Neuropathol. Exp. Neurol. 2000, 59, 815–821.
  21. Bello, M.; Rey, J.A.; de Campos, J.M.; Kusak, M. Chromosomal abnormalities in a pineocytoma. Cancer Genet. Cytogenet. 1993, 71, 185–186.
  22. Pfaff, E.; Aichmüller, C.; Sill, M.; Stichel, D.; Snuderl, M.; Karajannis, M.A.; Schuhmann, M.U.; Schittenhelm, J.; Hasselblatt, M.; Thomas, C.; et al. Molecular subgrouping of primary pineal parenchymal tumors reveals distinct subtypes correlated with clinical parameters and genetic alterations. Acta Neuropathol. 2020, 139, 243–257.
  23. Rahmanzade, R.; Pfaff, E.; Banan, R.; Sievers, P.; Suwala, A.K.; Hinz, F.; Bogumil, H.; Cherkezov, A.; Kaan, A.F.; Schrimpf, D. Genetical and epigenetical profiling identifies two subgroups of pineal parenchymal tumors of intermediate differentiation (PPTID) with distinct molecular, histological and clinical characteristics. Acta Neuropathol. 2023, 146, 853–856.
  24. Gras, E.; Catasus, L.; Argü, R.; Moreno-Bueno, G.; Palacios, J.; Gamallo, C.; Matias-Guiu, X.; Prat, J. Pineal Parenchymal Tumors Clinical, Pathologic, and Therapeutic Aspects. Cancer 1993, 72, 870–880.
  25. Ito, T.; Kanno, H.; Sato, K.-I.; Oikawa, M.; Ozaki, Y.; Nakamura, H.; Terasaka, S.; Kobayashi, H.; Houkin, K.; Hatanaka, K.; et al. Clinicopathologic Study of Pineal Parenchymal Tumors of Intermediate Differentiation. World Neurosurg. 2014, 81, 783–789.
  26. Tsumanuma, I.; Tanaka, R.; Washiyama, K. Clinicopathological study of pineal parenchymal tumors: Correlation between histopathological features, proliferative potential, and prognosis. Brain Tumor Pathol. 1999, 16, 61–68.
  27. Yu, T.; Sun, X.; Wang, J.; Ren, X.; Lin, N.; Lin, S. Twenty-seven cases of pineal parenchymal tumours of intermediate differentiation: Mitotic count, Ki-67 labelling index and extent of resection predict prognosis. J. Neurol. Neurosurg. Psychiatry 2016, 87, 386–395.
  28. Zhu, L.; Ren, G.; Li, K.; Liang, Z.; Tang, W.; Ji, Y.; Li, Y.; Cheng, H.; Geng, D. Pineal Parenchymal Tumours: Minimum Apparent Diffusion Coefficient in Prediction of Tumour Grading. J. Int. Med. Res. 2011, 39, 1456–1463.
  29. Lutterbach, J.; Fauchon, F.; Schild, S.E.; Chang, S.M.; Pagenstecher, A.; Volk, B.; Ostertag, C.; Momm, F.; Jouvet, A. Malignant Pineal Parenchymal Tumors in Adult Patients: Patterns of Care and Prognostic Factors. Neurosurgery 2002, 51, 44–56.
  30. Lee, J.C.; Mazor, T.; Lao, R.; Wan, E.; Diallo, A.B.; Hill, N.S.; Thangaraj, N.; Wendelsdorf, K.; Samuel, D.; Kline, C.N.; et al. Recurrent KBTBD4 small in-frame insertions and absence of DROSHA deletion or DICER1 mutation differentiate pineal parenchymal tumor of intermediate differentiation (PPTID) from pineoblastoma. Acta Neuropathol. 2019, 137, 851–854.
  31. Mena, H.; Rushing, E.J.; Ribas, J.L.; Delahunt, B.; Mccarthy, W.F. Tumors of pineal parenchymal cells: A correlation of histological features, including nucleolar organizer regions, with survival in 35 cases. Hum. Pathol. 1995, 26, 20–30.
  32. Miller, S.; Ward, J.H.; Rogers, H.A.; Lowe, J.; Grundy, R.G. Loss of INI1 Protein Expression Defines a Subgroup of Aggressive Central Nervous System Primitive Neuroectodermal Tumors. Brain Pathol. 2013, 23, 19–27.
  33. Herrick, M.K.; Rubinstein, L.J. The cytological differentiating potential of pineal parenchymal neoplasms (true pinealomas). A clinicopathological study of 28 tumours. Brain 1979, 102, 289–320.
  34. Garibotto, F.; Pavanello, M.; Milanaccio, C.; Gaggero, G.; Fiaschi, P. Management of hydrocephalus related to diffuse leptomeningeal glioneuronal tumour: A multifaceted condition. Child’s Nerv. Syst. 2021, 37, 1039–1040.
  35. Jakacki, R.I.; Burger, P.C.; Kocak, M.; Boyett, J.M.; Goldwein, J.; Mehta, M.; Packer, R.J.; Tarbell, N.J.; Pollack, I.F. Outcome and prognostic factors for children with supratentorial primitive neuroectodermal tumors treated with carboplatin during radiotherapy: A report from the Children’s Oncology Group. Pediatr. Blood Cancer 2015, 62, 776–783.
  36. Farnia, B.; Allen, P.K.; Brown, P.D.; Khatua, S.; Levine, N.B.; Li, J.; Penas-Prado, M.; Mahajan, A.; Ghia, A.J. Clinical Outcomes and Patterns of Failure in Pineoblastoma: A 30-Year, Single-Institution Retrospective Review. World Neurosurg. 2014, 82, 1232–1241.
  37. Tate, M.; Sughrue, M.E.; Rutkowski, M.J.; Kane, A.J.; Aranda, D.; McClinton, L.; Barani, I.J.; Parsa, A.T. The long-term postsurgical prognosis of patients with pineoblastoma. Cancer 2012, 118, 173–179.
  38. Brown, A.E.; Leibundgut, K.; Niggli, F.K.; Betts, D.R. Cytogenetics of pineoblastoma: Four new cases and a literature review. Cancer Genet. Cytogenet. 2006, 170, 175–179.
  39. Miller, S.; Rogers, H.A.; Lyon, P.; Rand, V.; Adamowicz-Brice, M.; Clifford, S.C.; Hayden, J.T.; Dyer, S.; Pfister, S.; Korshunov, A.; et al. Genome-wide molecular characterization of central nervous system primitive neuroectodermal tumor and pineoblastoma. Neuro-Oncology 2011, 13, 866–879.
  40. de Kock, L.; Sabbaghian, N.; Druker, H.; Weber, E.; Hamel, N.; Miller, S.; Choong, C.S.; Gottardo, N.G.; Kees, U.R.; Rednam, S.P.; et al. Germ-line and somatic DICER1 mutations in pineoblastoma. Acta Neuropathol. 2014, 128, 583–595.
  41. Snuderl, M.; Kannan, K.; Pfaff, E.; Wang, S.; Stafford, J.M.; Serrano, J.; Heguy, A.; Ray, K.; Faustin, A.; Aminova, O.; et al. Recurrent homozygous deletion of DROSHA and microduplication of PDE4DIP in pineoblastoma. Nat. Commun. 2018, 9, 2868.
  42. Li, B.K.; Vasiljevic, A.; Dufour, C.; Yao, F.; Ho, B.L.B.; Lu, M.; Hwang, E.I.; Gururangan, S.; Hansford, J.R.; Fouladi, M.; et al. Pineoblastoma segregates into molecular sub-groups with distinct clinico-pathologic features: A Rare Brain Tumor Consortium registry study. Acta Neuropathol. 2020, 139, 223–241.
  43. Liu, A.P.Y.; Gudenas, B.; Lin, T.; Orr, B.A.; Klimo, P.; Kumar, R.; Bouffet, E.; Gururangan, S.; Crawford, J.R.; Kellie, S.J.; et al. Risk-adapted therapy and biological heterogeneity in pineoblastoma: Integrated clinico-pathological analysis from the prospective, multi-center SJMB03 and SJYC07 trials. Acta Neuropathol. 2020, 139, 259–271.
More
Information
Subjects: Oncology
Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register : , , , , , , , , ,
View Times: 55
Revisions: 2 times (View History)
Update Date: 27 Feb 2024
1000/1000