Gonzales MF [1] first classified intracranial tumors according to their gross appearance. Zülch KJ [2] was the first to classify brain tumors according to their cellular constituents and introduce the term ‘glioma’. The first classification of brain tumors was formulated by Bailey and Cushing in [3]. In the years that followed the introduction of Bailey and Cushing’s classification, the diversity of histological appearances in primary neuroepithelial tumors even within one diagnostic category was widely recognized. Bailey and Cushing in [3] first used by the term “medulloblastoma” described a series of tumors found in the cerebella of children which was used synonymously with MSRCT. Bailey and Cushing [3], Russell DS et al. [4] attempted to classify tumors on the basis of their morphology and histopathological grade. Their system was based mainly upon autopsy material and correlated histological features to clinical prognosis. Even though these classification systems are generally adequate for the descriptions and diagnosis of most brain tumors their underlying concepts are not fully tenable in light of current knowledge. To overcome this, Zulch and an international team published the first WHO classification of tumors of the CNS in 1979 in their book “Histological Typing of Tumors of the Central Nervous System”, which was revised in 1985 and in 1993, the World Health Organization (WHO) published a revision. This was a significant revision from the original work, issued first in 1979.Kleihues and Cavenee in 1997 released a book [5] combining pathology and genetics with clear definition and grading of each tumor entity of the nervous system was published, subsequent modification was done in 2000 by them and their international team.

CLASSIFICATION OF MSRCT IN CNS (COMPILED FROM WHO-2000)

Embryonal tumors

Medulloblastoma (MB)

Supratentorial primitive neuroectodermal tumor (sPNET)

Atypical teratoid / rhabdoid tumor (AT/RT)

Ependymoblastoma

Medulloepithelioma

Pineal Parenchyma Tumors

Pineoblastoma

Neuroblastic Tumors

Olfactory neuroblastoma (esthesioneuroblastoma)

Germ Cell Tumors

Germinoma

Embryonal carcinoma

Yolk sac tumor (endodermal sinus tumor)

Lymphomas and Haemopoietic Neoplasms

Malignant lymphomas

Plasmacytoma

Glial tumors of Uncertain origin

Astroblastoma

Mixed Gliomas and Astrocytic Tumors

Anaplastic (malignant) oligoastrocytoma

Small cell GBM

Metastatic tumors

MIMICS OF MSRCT (Histopathological)

·       Gangliocytoma/Ganglioglioma

·       Desmoplastic Infantile Ganglioglioma

·       Central Neurocytoma

·       Paraganglioma

·       Pineocytoma

Brain Tumor Grading

The Ringertz classification first published in 1950 is a three grade system where grade I is the same as the WHO classification, but WHO grades II, III and IV are split between Ringertz grades II and III.

The St Anne/Mayo system from 1988 is also known by the names of hits authors, Daumas and Duport [6]. This system is based on four criteria—atypia, necrosis, mitosis and endothelial proliferation. There is a potential score of 0 4 in this system.

The Table shows both WHO histologic typing and ICD-O 6^th digit Grade

BIOLOGICAL GRADING OF CNS TUMORS

The diagram summarizes the main features of tumors grouped together by grade. Grade I tumors are circumscribed (encapsulated or not) and exhibit moderate cellularity, reflecting slow growth. Grade II tumors also have moderate cellularity, but their margins are poorly-defined or diffuse. Grade III tumors contain one or more “anaplastic” foci that have developed within a pre-existent low grade tumor (I or II). Grade IV tumors are characterized by very marked anaplasia that may be generalized (up to the margins of the tumor mass) or focal (within a pre-existent tumor of lower grade).

Brain Tumor Staging

Basically, all brain tumors are considered localized unless they cross the midline or the tentorium or unless they are described as having “drop” metastases in the spinal cord.

There was a TNM staging for brain tumors in the fourth edition of the AJCC Manual for Staging of Cancer55 based heavily on the tumor grade, but this was withdrawn in subsequent editions.

TNM

None in 5^th or 6^th editions.

The Collaborative Staging System uses two fields to code the extent of disease for tumors of the brain and cerebral meninges. The extension field includes a code for benign brain tumors to meet the needs of cases that will be reported as of 2004.

WORKING CLASSIFICATION

(for clinician can be derived from the following grouping)

Supratentorial Tumors

Hemispheric – Astrocytoma, Sarcoma, Meningiomas

Midline – Craniopharyngioma, Optic glioma, Pineoloma, Ependymoma.

Infratentorial Tumors

Cerebellar and Fourth ventricle – astrocytoma, medulloblastoma

Brain stem glioma

Metastatic tumors

Generalized disease with brain tumor component – von Recklinghausen’s disease, Tuberous sclerosis

AETIOLOGY OF CNS TUMORS

Unknown (most tumors)

Developmental abnormality

Teratomas, teratoid tumors, dermoid, epidermoid cysts, craniopharyngiomas, chordomas.

Ganglioneuromas, gangliogliomas, nasal gliomas.

Hamartomas, lipomas, angiomas (hamartomas of blood vessel origin),

Hereditary

Haemangioblastomas in von Hippel-Lindau’s disease

Tumors in neurofibromatosis

(von Recklinghausen’s disease)

Tumors in tuberous sclerosis

(Bourneville-Pringle disease)

Immunosuppression

Lymphomas, gliomas? (Previous TB)

Carcinogenic substances (Experimental)

Often mixed type glioma, meningiomas, nerve sheath tumors.

Virus induced (Experimental)

Medulloblastomas, neuroblastomas, choroid plexus papillomas, gliomas, sarcomas.

Irradiation

Meningiomas, sarcomas, glioblastomas (In monkeys), giant cell

glioblastomas

Note:  No apparent association exists between smoking and brain tumor [7]

SEX

Male predominance (M: F = 1.4) except for meningiomas.

Approach to Diagnosis of CNS Tumors

Relevant History

Patient Age

Most central nervous system (CNS) tumors show an age predilection, and patient age has been shown to predict survival in many malignant CNS neoplasms. With diffusely infiltrating astrocytic tumors, age followed by histologic grade represent the 2 strongest prognostic indicators for patient outcome, with patient age older than 50 years and high-grade tumors serving as negative indicators.

Duration of Symptoms

(Acute or Chronic).—A long clinical history of CNS symptoms or seizures prior to the diagnosis of a CNS tumor favors a slowly growing neoplasm that is more likely to be benign. A rapidly progressive neurological deficit of sudden onset is more consistent with, but not always indicative of, a high-grade malignant tumor.

Extent of Resection

For most CNS tumors, the amount of tumor removed (total, subtotal, or partial resection) is an important predictor of patient outcome [8].

Tumor Location and Size

The extent of surgical resection possible is determined by tumor location and size.

• Location – intra-axial vs extra-axial
• Site CPA, Convexity, intraventricular etc.
• Number single vs multiple,
• Radiologic features- enhancing vs non-enhancing
• Is it abnormal? / Is it tumor or non-neoplastic disease?/ If tumor, is it primary or metastatic?

Previous Diagnosis

Knowledge of the presence or absence of extracranial disease, that is, a history of immunosuppression or a history of a primary malignant neoplasm outside the CNS, can be critical in the correct interpretation of biopsy material.

Previous CNS Biopsies

History of radiation or radiosurgery

Knowledge of prior radiation therapy or radiosurgery can help in interpreting specimens in which there are large areas of radiation change (eg, coagulative necrosis, gliosis, vascular hyalinization). Central nervous system tumors noted to arise in a field of prior irradiation include meningiomas, meningeal sarcomas, astrocytomas, primitive neuroectodermal tumors, and gliosarcomas. Radiation therapy of diffusely infiltrating astrocytomas has been shown to increase survival.

Family History of Cancer or Primary CNS Tumors.           

Relevant Findings

Imaging Features (density; enhancement pattern; well-circumscribed or infiltrative borders; cyst formation; calcification; location [intraventricular]; white matter, gray matter, or both).—Recognition of characteristic imaging patterns and locations of CNS tumors is important in correct interpretation of biopsy specimens, for example, low-grade infiltrating astrocytomas usually do not enhance, whereas high-grade ones do. Tumor enhancement and peritumoral edema in infiltrating astrocytomas are associated with a worse prognosis, and diffuse tumors have been shown to have a poorer prognosis than focal ones.

Specimen Unfixed/Fixed

Cytologic Material. — Cytologic preservation in cerebrospinal fluid depends on the time interval before processing, especially for hematopoietic and some neuroepithelial cells.

Biopsy or Resection

Cellular detail is very important for interpreting CNS neoplasms, and previously frozen tissue is suboptimal, especially for grading and subclassifying gliomas. Make every attempt to retain tissue that has not been previously frozen for permanent sections. Avoid using sponges in cassettes because they produce angular defects, which resemble vascular/luminal spaces in the final sections. Wrapping small biopsies in lens paper prior to placing them in cassettes is recommended [9].

Cytologic Material Submitted for Microscopic Evaluation

Cytospin slides or liquid-based monolayer cytology, both air-dried Romanowsky-stained and fixed Papanicolaou-stained slides, as well as unstained slides, should be prepared from fluid specimens, especially cerebrospinal fluid, meningeal fluid, and tumoral cyst fluid.

Special Studies

It may be necessary to divide biopsy/resection tissue into portions for the following procedures

Squash, touch, or scrape preparations

Unfrozen permanent paraffin sections

Frozen sections, if requested

Electron microscopy (Retain a small portion in 3% glutaraldehyde or “embed and hold” for electron microscopy if necessary)

Other (microbiology, flow cytometry, cytogenetics, molecular diagnostics)

Molecular diagnostic studies

Frozen tissue, if requested (freeze fresh tissue as soon as possible and store at −70°C), especially for possible future molecular diagnostic studies

Squash Preparations

Squash preparations are prepared by placing a tiny (1–2 mm) fragment of tissue onto a glass slide, placing another glass slide over it, pressing the slides together, squashing the tissue between them, then sliding the 2 slides past each other, dragging squashed tissue across each slide. Slides are then rapidly placed into fixative in the same rack used for frozen sections and stained as for frozen sections [3].

Molecular diagnostic testing is playing an increasingly important role in the diagnosis, staging, and treatment of tumors.

Comment

Correlation of clinical and radiographic information should be critically reviewed before final sign-out of the biopsy diagnosis [10].

After patient age, tumor histology and grade have been shown to be the strongest predictors of clinical course [11]. Several grading systems have been proposed, based on their ability to define distinct patient groups with significantly different survival curves. Both 3-tiered and 4-tiered systems are currently in use and have been reviewed [12]. Two examples of popular grading systems are shown below. For a complete review and comparison of these systems, including the 3-tiered system such as the Ringertz system and modifications thereof, the reader is referred to the review by Kleihues P et al. [13] Comparison of the WHO and St. Anne/Mayo Grading Systems for Astrocytomas.

Other Pathologic Features

Hemosiderin deposition, calcification, and microcyst formation are nonspecific findings that occur in both malignant and benign CNS neoplasms. The presence of gemistocytes, vascular proliferation, and necrosis represent negative prognostic indicators. Malignant and atypical meningeal tumors often invade brain substance [13].

Immunohistochemical (IHC) staining [14]

Most immunocytochemistry is used to investigate cellular differentiation in tumors. Diagnostic immunocytochemistry is best performed using a panel of antibodies, particularly for tumors which are difficult to classify using standard tinctorial methods

Electron Microscopy [15]

Electron microscopy has a rather limited role to play in the practical diagnosis of CNS tumors and is hampered by the constraints of time, expense, specialized fixation, and the expertise required for ultrathin section preparation.

Special investigations

• Evaluation of proliferative index – MIB-1 best, DNA Topoisomerase II a, PCNA,Ki-67
• Molecular genetics
• Alterations in oncogenes / Tumor suppressor genes
• Protein product alterations
• Markers of invasion
• Markers of angiogenesis

This is a prospective study as well as retrospective study of MALIGNANT SMALL ROUND CELL TUMOR of the Central Nervous System at our Grant medical college over a period of 10 years from 01/01/1997 to 10/10/2006.

In this category of MSRCT’S of CNS, we have included all the tumors which histologically present as “Cellular Blue Tumors”. Going through the WHO classification, we realized that there are many tumors which can be included in this category and pose problem in their accurate diagnosis.

MIMICS OF MSRCT (Histopathological)

·           Gangliocytoma/Ganglioglioma

·           Desmoplastic Infantile Ganglioglioma

·           Central Neurocytoma

·           Paraganglioma

·           Pineocytoma

The clinical data compiled and summarized in the following form:-

What history is available?

Age/Sex

Location-Intraaxial/Extraaxial

Site-CPA/Convexity, Intraventricular etc

Number- Single/Multiple

Radiologic features (CT/MRI)

Enhancing/Non-enhancing

Is it abnormal?

Is it a tumor or non-neoplastic lesion?

If tumor, is it primary or metastatic?

Histology of all of these cases was reviewed meticulously under the following headings:-

Routine H/E stain used for-

Areas of Haemorrahage and Necrosis

Pattern

Difuse / Focal

Cohesive / Discohesive

Rosette formation / Type of Rosettes

Neural tube seen / not seen

Perivascular pattern

Sheets / Glandular / Alveolar

Cellular Morphology

Size of cell

Monomorphism/Pleomorphism

Amount and character of cytoplasm

Evidence of differentiation

(e.g. rhabdoid, squamoid, adenamatoid)

Nuclear details

Nuclear membrane

Nuclear chromatin / Distribution

Nucleoli-size

Mitotic activity

Retic stain

Pattern useful for diagnosis of

Desmoplastic Medulloblastoma / MBEN

Lymphoma

Metastasis

PTAH stain

For evidence of glial differentiation in Medulloblastoma

Confirm glial / non glial origin of tumor

Negativity favored Metastasis

Bilchowsky stain

For neuronal/ganglionic origin

Immunohistology

Was not done, except for few cases of Lymphomas. Utilizing the above criterias we have attempted to subcategorize MSRCT’S of CNS.

This study was undertaken with a view of evaluating and sub-characterizing the broad category of Malignant Small Round Cell Tumor of the CNS. Our findings are completely based upon histological diagnosis.

Incidence of MSRCT

Our study includes total of 129 cases of MSRCT in last 10 years which constitute 6.80% of all the brain tumors received in our department. (TABLE NO- 1). This incidence is in concordance with the study done by CBTRUS-2004 [37] who has recorded the incidence of 6 - 7%.

Out of the total number of tumor cases (=1897) in our neuropathology department between 1996-2006, Embyonal/Primitive/ Medulloblastoma constituted 4.3% as against 1.8%, lymphomas constituted 0.95% against 3.3%, germ cell tumor 0.42% against 0.6% and metastasis constituted 0.42% against 0.5% of total number of brain tumor (TABLE NO-2). The above is quoted by the study conducted in the West by Central Registry [3].

Age Incidence

The maximum number of cases were in the young age group (0-20 yrs) followed by middle age(21-50yrs) constituting 54.3% and 35.4% respectively (TABLE NO-3), (TABLE NO- 5); this is in concordance with study by central US registry and Kleihues, WHO [5].

The Mean age group of presentation of MSRCT in the CNS is 23 years in our study, this has not been stated anywhere in Western and Indian literatureIn our study, majority of cases in the younger age groups were Medulloblastoma and sPNET with few rare cases like pineoblastoma, ependymoblastoma, germ cell tumor and Atypical Teratoid/Rhabdoid Tumor), (TABLE NO- 6).

However surprisingly though MSCRT is supposed to be uncommon in elderly age group(>50yrs) we encountered around 9.3% (TABLE NO- 3) of MSRCT in this age group which is higher as compared to 4%-5% quoted by CBTRUS-2004 [37].

The peak incidence in our study was in the middle age group (21-40yrs) that was 11/18 cases (61%), followed by elderly and then young age, implying our patient had died before these tumor developed due to severe complications of HIV infection, including oppurtunistic infection, most commonly Tuberculosis, in INDIA [18].

Sex Incidence

In our study M: F was 3:1(96 males against 33 females) indicating higher prevalence in the male (TABLE NO-4). (TABLE NO-5) as against 1.5-2:1 calculated from the study by Central Brain tumor registry, United States in the year 1997-2001.

Location

Of the 129 cases reviewed the most common location of involvement of MSRCT in the CNS is infratentorial accounting to 49% followed by supratentorial, (40%) spinal (9%), scalp (2%) and nasal (1%) respectively (TABLE NO-7,8). This is because most of our cases were medulloblastomas which are cerebellar (infratentorial) in location [19]. For the same reason most of our patient presented clinically with cerebellar signs viz. Headache, Vomiting and Ataxia which appeared as a most usual clinical manifestation in our patients (TABLE NO-9)

As far as the radiological correlation is concerned we found that radiodiagnosis (CT/MRI) showed excellent correlation with medulloblastoma (TABLE NO-10.

MEDULLOBLASTOMA

Incidence

Medulloblastoma is the most common type of MSRCT encountered in our study. We reviewed a total of 57 cases of Medulloblastoma, this accounted to 44.19% of MSRCT and 3.00% of total number of CNS tumor cases we received in our neuropathology department (TABLE NO-2).

Age and sex distribution (TABLE NO-6)

The overall mean and median age at diagnosis for MBs is 13 years and 11 years respectively, with the peak age of occurrence being around 9 years.The study in West by F.Giangaspero [20] states that medulloblastomas occur in children younger than 16 years and the peak occurrence is at 7 years.Of the adult patients, majority (80%) are in late adolescence or early adulthood (range 21 to 47 years with median of 25 years) the findings are similar to the one quoted by WHO.These tumors rarely occur beyond the fifth decade of life.

Of the 57 cases of MBs in our study 41 were males and 16 were females (M: F=3-3.5:1).So, our study males constituted around 71% which correlates with 65% stated by WHO [5].

Location (TABLE NO-7, 8)

Of the total of 57 cases of medulloblastoma 42 were from cerebellar vermis accounting to 76.36 % (TABLE NO-11). This is in concordance with WHO study [5] that states MBs in 75% of cases arise in the cerebellar vermis.Of the 42 cases 38 were seen in children less than 21 years of age constituting to 90%.Rest of the 15 cases showed involvement of cerebellar hemispheres and all these cases were seen in adults.This is in concordance with Joo KM et al. [21]  who have quoted that ” hemispheric or lateral location is more common in older children, adolescents and adults”

Radiodiagnosis

CT/MRI of 52 out of 57 cases (91.23%) of Medulloblastomas showed excellent correlation with histopathological diagnosis. (TABLE NO -10). About 77.19% of MBs were located in midline in the cerebellum vermis.93% of Medulloblastomas showed marked contrast enhancement in CT scan. 89.47% of Above parameters are in concordance with the studies done by Blaser SI, Harwood-Nash DC [22].

Histopathological Features

Of the 57 cases of medulloblastoma, classical medulloblastoma contituted 68.42 % (39/57cases), desmoplastic 26.32 % (15/57 cases) and few cases were of Medulloblastoma with extensive nodularity of 5.26 %. (3/57 cases) (TABLE NO-13). The clinical outcome depends upon histological type-nodularity indicates better prognosis [Kleihues P, Cavenee WK [13].

Classic Medulloblastoma (Fig-1)

The classic medulloblastomas were composed of densely, packed cells with round to oval or carrot-shaped nuclei and scant cytoplasm.

Desmoplastic Medulloblastoma (Fig-2)

This variant of medulloblastoma was characterized by a dense intercellular network of reticulin fibres with lucent, reticulin free islands which contain tumor cells.

Medulloblastoma with Extensive Nodularity (Fig-3)

There is increasing evidence that clinical outcome may, to some extent, depend on the histological type of medulloblastoma. Our findings are consistent with studies in the west conducted by Lantos P et al. [28]; Kleihues P, Cavenee WK [5]; quotes ‘Desmoplastic medulloblastomas were associated with a somewhat better outcome in some series, but with poor prognosis in others’.

Primary CNS lymphomas

Incidence (TABLE NO-2)

Of the total of 129 cases of MSRCT we came across 18 cases of CNS lymphomas accounting to 13.95% of MSRCTs in the CNS and 0.95% of total number of CNS tumors received in our department in last 10 years (Table No- 2). All our cases were immunocompetent, non HIV/AIDS associated cases. Our study is in concordance with another study in India [Shankar] who studied 11 patients with PCNSL and none of them were associated with HIV/AIDS.

In contrast, the reason of increasing percentage of lymphomas in Western countries is due to HIV/AIDS¹ and the fact that patients survive due to anti retro viral therapy [16] state-Previously, a rare tumor accounting for less than 2% of cerebral neoplasms, PCNSL is being seen with increasing frequency in immunocompetent patients, patients with AIDS, and transplant recipients, accounted for 2.7% of all primary brain tumors diagnosed in the United States from 1995-1999 (CBTRUS 2002-2003). In India, we notice less number of cases of the CNS LYMPHOMAS associated with HIV because most of our patient had die at a young age due to severe complications of HIV infection, including oppurtunistic infection, most common of which is Tuberculosis [18].  

Age and sex distribution (TABLE NO-6)

Primary CNS lymphomas affect all ages, the peak incidence in our study was in the middle age group (21-40yrs) that was 11/18 cases (61%), followed by elderly and then young age; this is unlike Western studies where maximum number of cases were seen in elderly age group for obvious reasons as already stated above. Of the 18 cases of lymphomas 16 were males and 2 were females. (M: F =8: 1). We found male preponderance like other studies but the ratio was not in accordance with any of the studies in West, W. Paulus and collegues [17] by WHO that states male: female ratio of 3:2 and 140) Maher EA, Fine HA states it to be 2:1.

Location (TABLE NO-7, 8)

About 66% of primary CNS lymphomas involve the supratentorial space (12/18cases), including the frontal (5/12), parietal (2/12) lobes, basal ganglia / periventricular regions (3/12) and corpus callosum (1/12), the posterior fossa (3/12), and the spinal cord (3/12) (TABLE NO -14) .1 case was having bi-thalamic involvement. Frontal lobe was commonest site for involvement in our study. Our study is in accordance with studies done by W. Paulus and collegues [16] by WHO.

Radiodiagnosis

CNSLymphoma is one of the most underdiagnosed tumor on neuroimajing, this could be due to that fact that it mimics any any grade IV tumor. Only 3 out of 18 cases showed radiological correlation accounting to 16.67% (TABLE NO -10). No data of this kind of comparison was found in the Western literature.

Histopathological Features (Fig-4, 5, 6, 7)

Of the 18 cases of lymphomas, the diffuse large cell lymphomas was the commonest in our case 14/18 (77.8%), 1 case of lymphoblastic lymphoma. These were high grade lymphomas which could be classified as per the REAL and WHO classification. Of large cell lymphomas, in only 7 cases immunohistochemistry was done and showed expression of pan – B markers.Interestingly we had 3 cases(16.7%) of small cell lymphoplasmacytic lymphoma(TABLE NO -15 ) .

Our study correlates with the Western studies done by many authors [16]^, as well as Indian authors.

All our 14 cases of large cell Lymphoma showed that diffuse infiltration of brain parenchyma in an angiocentric pattern forming collars of tumor cells within concentric perivascular reticulin deposits.

B-cell lymphomas

Immunohistochemistry was done in 7 cases and were all found to be positive for pan-B markers Approximately 98% of primary CNS lymphomas are B-cell lymphomas with immunohistochemical expression of pan – B markers such as CD20 [24]. Lantos P, Louis DN, Rosenblum MK, Kleihues P [25]; Kleihues P, Cavenee WK [16] state that “Most tumors correspond to diffuse large B- cell Lymphoma of the REAL classification.”, they also state that “the vast majority of primary CNS lymphoma in immunocompetent patients is diffuse large B-cell lymphoma”

T-cell lymphomas

We did not come across any case of T-cell lymphomas.

Plasmacytoma (Fig-12)

We came across 3 cases of plasmacytoma in our study and none of which were intracranial.All our cases involved the spinal cord.     

Angiotropic lymphoma

We did not come across any case of Angiotropic lymphoma.

Hodgkin disease

The diagnosis of Hodgkin disease rests upon the identification of Reed – Sternberg cells or their variants in the appropriate background of non-neoplastic haematopoietic cells (lymphocytes, plasma cells, histiocytes, eosinophils.

MALT lymphoma of the dura

We did not come across any case of MALT lymphoma.

SUPRATENTORIAL PRIMITIVE NEUROECTODERMAL TUMORS (sPNET)

Incidence (TABLE NO-2)

Of the total of 129 cases of MSRCT, sPNET were 15 in number i.e. 11.6% of MSRCT and 0.8% of the total number of CNS neoplasms (Table No-) this is much less than the 3.6-6% mentioned in different literature in West -10 out of 178(5.6%) (Rorke, unpublished observation) [16].

Age and sex distribution (TABLE NO-6)

Of the 15 cases the commonest age of presentation was between 0-10 yrs 7/15 (around 45%) followed by 21-30 4/15 around 26% (Table No-). The mean age of presentation was more than that in the West i.e 15.5 yrs as against the Western data that states the age range for cerebral-suprasellar PNETs is 4 weeks to 10 years, with a mean of 5.5years

Of the 15 cases 14 were males and 1 was female as against Western studies which state the male: female ratio is 2:1. This is probably because the number of cases in our case were n<30.

Location (TABLE NO-7,8)

As the terminology, these tumors are found in the supratentorial space occupied by the cerebrum or suprasellar region.

Neuroimaging (TABLE NO -10)

In all our cases CT / MRI together were effective in diagnosing sPNET in around 26.67% of cases i.e only 4 out of 15 cases (Table No-10).as this is a recently categorised entity by WHO.

Histopathology (Fig-8)

Light microscopic features of cerebral sPNETs are basically similar to medulloblastomaThe primitive cells were observed growing in sheets or cords of dense cellularity with increased mitotic index and increased nuclear-cytoplasmic ratio or even angular configurations of nuclei. Nucleoli were seen in few cases. Our findings are consistant with studies in the west conducted by, Lantos P, Louis DN, Rosenblum MK, Kleihues P [28]; Kleihues P, Cavenee WK [13].

PINEOBLASTOMA

Incidence (TABLE NO-2)

In our study we received 7 cases of Pineoblastomas of 129 MSRCT accounting to 5.4% of MSRCT and 0.4% of total number of CNS neoplasms (Table No-). This is slightly higher than CBTRUS-2001 which states the incidence to be 0.2%. This could be due to small sample size (<30) in our case.

Age and sex distribution (TABLE NO-6)

We came across patients with age groups ranging from 6 months to 40 years with the mean age of 21 years with a peak between 12-20 years (Table No-6). This is in concordance with the study done in the West by Peter Lantos, Paul Kleihues [28]. They state the preponderance to be more in the first 2 decades and few cases in late adulthood.

Of the 7 cases reviewed in our study were 4 males and 3 females (Table No-6), hereby indicating slight male preponderance, this is in accordance with most of the studies which states males are more commonly affected [16].

Neuroimaging (TABLE NO -10)

On T1 weighted MRI scan, pineoblastomas the hypo-to-isointense but are heterogeneous upon contrast administration. The high sensitivity and specificity has been also stated by Neuwelt EA, Glasberg M [26].

Histopathology (Fig-9)

All our cases of Pineoblastomas were highly cellular neoplasms resembling other small cell, embryonal and primitive neuroectodermal tumors of the CNS, composed of patternless sheets of densely packed small cells with round to irregular nuclei and scant cytoplasm. Pineocytomatous rosettes were lacking in all our case, although Homer-Wright and Flexner-Wintersteiner rosettes were seen in few. Necrosis was a common feature in our cases but mitotic activity was variable. Our findings are consistant with studies in the west conducted by Kleihues P [5]; Neuwelt EA, Glasberg M, [26], Kleihues P, Cavenee WK [16].

CNS GERM CELL TUMORS [27]^\

Incidence (TABLE NO-2)

In our study we received 8 cases of Germ cell tumor of 129 MSRCT accounting to 6.2% of MSRCT and 0.4% of total number of CNS neoplasms. In the West, they constitute only 0.3-0.6% of all primary intracranial neoplasms [16].

Age and Sex distribution (TABLE NO-6)

We came across patients with age groups ranging from 1 year to 31 years with the mean age of 20 years with a peak at 10 years (TABLE NO-6). This is in concordance with the study done in the West Paul Kleihues [16]. They state that the CNS germ cell tumors are primarily neoplasms of the young approximately 90% afflict those younger than 20 years. (Peak 10-12 years).

Of the 8 cases we studied, there were 5 males and 3 females thereby indicating slight male preponderance. This is in concordance with the study in the West by many authors. In the West when the CNS as a whole is considered, the male to female ratio is 2-2.5:1 however, the regional distribution of these tumors varies according to sex [28, 16].

Location (TABLE NO-7,8)

In noted that all our cases of Germ cell Tumor were midline in location. Out of the 8 cases of germ cell tumor 7 were above the third ventricle and 1 below it [4 suprasellar, 3 pineal and 1 posterior fossa] (TABLE NO -16).

This corresponds to 87.5% of tumors above third ventricle. This is in concordance with the study done by Rosenblum MK et al. [29] who found germ cell tumors above third ventricle in 80% of their cases.

Neuroimaging (TABLE NO -10)

Radiological diagnosis of germ cell tumors in our study was made only in 2 out of 8 cases which account to be 25% only (low specificity). This is due to the fact that the neuroradiological profiles of CNS germ cell tumors are largely non-specific, and definitive histological subclassification requires tissue examination [30, 31].

Histopathology (Fig-10)

Germinoma / dysgerminoma, embryonal carcinoma, and Yolk sac tumor are considered here as they form differential of MSRCT.

Germinoma

All our cases of germinoma showed large undifferentiated cells resembling primodial germinal elements composed of uniform tumor cells resembling primitive germ cells, with large, vesicular nuclei, prominent nucleoli and a clear, glycogen-rich cytoplasm.

Yolk Sac Tumor

Our case was composed of loose, variably cellular primitive appearing epithelial cells in solid sheets representing yolk sac endoderm around a conspicuously myxoid matrix. Schiller – Duval bodies were not seen in our case. Our findings are consistant with studies in the west conducted by Lantos P, Louis DN, Rosenblum MK, Kleihues P [28], Kleihues P, Cavenee WK [13].

Embryonal Carcinoma

We did not come across this variant of Germ Cell Tumor.

OLFACTORY NEUROBLASTOMA

Incidence, age and sex distribution (TABLE NO-2), (TABLE NO-6) 

In our study we came across 4 cases of olfactory neuroblastoma accounting to 3.1% of MSRCT and 0.2% of total number of CNS tumors referred to our department in last 10 years (Table No-). The exact prevalence of this tumor is not known as a relatively uncommon neoplasm, Kleihues P, Cavenee WK, eds. [5].

The age of those affected ranges from 20 to 60 years (Table No-) as against 2 to 90 years quoted by , Prasad N, et al., [32]. As in there study we also noted a bimodal age distribution, with cases tending to cluster around ages 20 and 50 years (Table No-).

Localization

All our cases of Olfactory neurobastoma involved the cribrirform plate.1 of our case showed infiltration of adjacent structures involving the paranasal sinuses, oro-nasopharynx, the base of skull, and even the cerebral frontal lobes. This kind of presentation is also stated by Prasad N, et al., [32].

Histopathology (Fig-11)

The typical microscopic appearance of olfactory neuroblastoma in our cases were that of a cellular tumor composed of uniform small cells with scant fibrillar cytoplasm and around dark nuclei. Tumor cells were arranged in lobules, containing scattered rosettes of the Homer-Wright type, less commonly, the tumor showed Flexner rosettes and other characteristics more typical of classic neuroblastoma. In contrast to neuroblastic growth pattern, olfactory neuroblastic growth pattern showed larger cells with distinct cytoplasm that have a solid growth pattern and impart a distinct epithelial quality. This basic pattern was modified by the presence of intersecting band of collagen leading to lobulation and Zell Ballen types of cellular organization, reminiscent of that of paraganglioma. Our findings are consistant with studies in the west conducted by, Lantos P, et al. [28], Kleihues P, Cavenee WK [5].

MEDULLOEPITHELIOMA

Age and Sex Distribution (TABLE NO-6) 

Although Molloy PT, et al. [33] observed that medulloepitheliomas typically affect children between 6 months and 5 years, with rare reports of congenital tumors. We came across 2 cases of this tumors in the age group of 41 to 50 years (TABLE NO-2).

Location (TABLE NO-7,8) 

We found 1 case in suprasellar and the other in spinal location. Molloy PT, Yachnis state that majority of medulloepitheliomas are located in the periventricular region and the remaining in the cerebral hemispheres. Isolated examples have been described in the cauda equina, presacral areas, posterior fossa and pons.

CT/MRI scan (TABLE NO -10)

Variable and non specific. No correlation was made out in our cases.

Histopathological (Fig-13)

Both the tumors had a very typical cytoarchitecture closely resembling embryonic or primitive neural tube. They were characterized by papillary, tubular and trabecular arrangements of the neoplastic pseudostratified neuroepithelium, having a external limiting membrane resting on a delicate reticulin framework. Mitoses were abundant and tend to be located more on the non-ciliated, reticulin-free luminal surface. Our findings are consistant with studies in the west conducted by Lantos P, Louis DN, Rosenblum MK, Kleihues P [28], Kleihues P, Cavenee WK [16].

EPENDYMOBLASTOMA

Age and sex distribution (TABLE NO-6)

We came across 2 cases (10 months and 25 years) of ependymoblastoma in our 10 year study (TABLE NO-2). Radkowski MA et al. [34] quote that the ependymoblastoma occurs in young children including neonates.

Location (TABLE NO-7,8)

Both our cases were large and located supratentorially. Mork SJ, Rubinstein LJ, [35] states that these neoplasms are often large and supratentorial.

Histopathology (Fig-14)

Diagnostic features were those of a central primitive neuroectodermal tumor with distinctive multilayed rosettes, with cells in the outer rim of the rosette merging with the surrounding undifferentiated neuroectodermal cells. The chief histological characteristic of ependymoblastoma was the dense cellularity with distinctive and numerous rosettes. Our findings are consistent with studies in the west conducted by Lantos P, Louis DN, Rosenblum MK, Kleihues P [5], Kleihues P, Cavenee WK [16].

AYPICAL TERATOID / RHABDOID TUMOR (AT/RT)

Incidence (TABLE NO-2)

We came across 2 cases (0.1%) of ATRT in last 10 years. Accurate data relative to incidence are difficult to obtain since this tumor has been generally misdiagnosed until the past few years. A total of188 cases had been reported by Giordana MT, et al. [38]. In total, 2.1% of a group of 930 primary CNS tumors in children 18 years or less, diagnosed at the Children’s Hospital of Philadelphia between July 1979 and June 1999, were AT/RT (Rorke, unpublished observation).

Age and sex distribution (TABLE NO-6)

Of the 2 cases observed in last 10 year 1 was an infant of 3 months female and 1 case of 54 years male. Rorke, unpublished observation state of 188 cases observed to date, 184 have been infants or children, 94% of whom were five years of age or less at diagnosis. The average age of the four adults was 32years (21-41 years). The male to female ratio in paediatric cases is 1.4:1; males were also predominant among the small group of adults, 3:1.

Location (TABLE NO-7,8)

Both of our cases were supratentorial in location. Rorke states that the location of the 184 primary childhood AT/RTs is as follows - posterior fossa, 52% (cerebellum, cerebello-pontine angle, and/or brainstem); supratentorial, 39% (cerebral or suprasellar); pineal, 5%, mulatifocal 2%, spinal, 2%.

Neuroimaging (TABLE NO -10)

Neither CT nor MRI was useful in our case. Findings on both computerized tomography (CT) and magnetic resonance imaging (MRI) are similar to those seen in patients with medulloblastoma.

Histopathology (Fig-15)

These were the tumors containing rhabdoid cells, with additional, variable components of primitive neuroectodermal, mesenchymal and epithelial cells.

Mesenchymal fields appeared as loose arrangements of small spindle cells. The epithelial tissue formed an adenomatous pattern suggestive of adenocarcinoma and may be confused with choroids plexus carcinoma. Our findings are consistant with studies in the west conducted by Lantos P, Louis DN, Rosenblum MK, Kleihues P [28], Kleihues P, Cavenee WK [5].

MALIGNANT MELANOMA (Fig-16) [16] (TABLE NO-6)                      

Of the 129 cases of MSRCT we came across 1 case (26 years Male) of Malignant Melanoma constituting to 0.1% of all CNS tumors received in our department in last 10 years (TABLE NO-2). Lantos P, Louis DN, et al. [28] states that malignant melanoma is a rare tumor in the CNS.

Our case showed considerable pleomorphism with large and bizarre tumor cells including multinucleated giant cells and a variable amount of melanin pigment. Also was seen high mitotic rate and necrosis, hemorrhage and invasion of brain or spinal cord parenchyma are common. Findings are consistant with Kleihues P, Cavenee WK [13].

ANAPLASTIC OLIGODENDROGLIOMA (Fig-17) [13] (TABLE NO-6)

Of the 129 cases of MSRCT we came across 1 case (26 years Male) of Recurrent Anaplastic Oligodendroglioma constituting to 0.1% of all CNS tumors received in our department in last 10 years (TABLE NO-2). Lantos P, et al. [28] states that “estimations of the incidence of anaplastic oligodendroglioma are diffcult because many studies do not clearly differentiate between WHO grade 11 oligodendroglioma and anaplastic oligodendroglioma.”

METASTATIC TUMORS OF THE CNS (Fig-18, 19) (TABLE NO-6)

Of the 129 cases of MSRCT we came across 8 cases of metastasis accounting to 6.2% of all CNS tumors received in our department in last 10 years (TABLE NO-2). Under this category we have included only those cases of metastasis which did not show any squamous or adenomatous differentiation and showed histological picture simulating MSRCT’S.

Lantos P, Louis DN, Rosenblum MK, Kleihues P [28], Kleihues P, Cavenee WK [5]  mention that the incidence of CNS metastases increases with age.We also noted the age in 6 out of 8 cases was more than 40 years of age. The male: female ratio for cerebral metastasis in our case was 1.67:1 (5 males and 3 females), 7 of our cases had cerebral metastasis and 1 had intraspinal metastasis (14 year male).as against study by Kleihues P, Cavenee WK [5], they state male: female ratio for cerebral metastasis is 1.36:1 while for intraspinal metastases a ratio of 1.16:1. The most common site of metastasis in our study was cerebrum followed by others (TABLE NO -17).

The distribution of metastasis to the brain in our cases was as follows oat cell carcinoma of Lung (1 case 50 years male), carcinoma Prostate (1 case 61 years male), Germ cell tumor (1 case 14 years male), undifferentiated carcinoma (52 years male) and 4 cases (1 male and 3 female) were kept under broad category of MSRCT (TABLE NO -18). Delattre JY, Krol G, Thaler HT [39] state that the most common primary cancers metastasizing to the brain are lung cancer (50%), breast cancer (15%-20%), cancer of unknown primary site (10%-15%), melanoma (10%), and colon cancer (5%).

MIMICS OF MSRCT (Fig-20)

The question is “What do we mean by mimics of Malignant Small Round Cell Tumors in CNS?” We have included this category as we encounter many tumors in neuropathology especially stereotactic biopsies where the tumor is composed of small cells without any differentiation. This category includes Central Neurocytomas, Paragangliomas and Pineocytomas.The other category is the one where the embryonal component is composed of small cells with focal ganglio-neuronal differentiation this includes Ganglioglioma, Gangliocytoma and DIG. The importance lies in the fact that the mimics form grade 1 tumors with excellent prognosis in contrast to MSRCT which are grade 4 neoplasms.

This is a prospective study as well as retrospective study of MALIGNANT SMALL ROUND CELL TUMOR of the Central Nervous System at our Grant medical college over a period of 10 years from 01/01/1997 to 10/10/2006.

Traditionally, Malignant Small Round Cell Tumors (MSRCT) of the CNS are synonymous with Medulloblastomas.Histologically they are characterised by cellular blue tumor.There is no broad category of MSRCT in WHO classification. The other aspect of the study was to identify the category of mimics which are grading 1 neoplasm simulating “Cellular Blue Tumors” on histology.

Intraoperative diagnosis using squash/frozen and postoperative diagnosis using histopathology still remains a primary diagnostic modality, with judicious and meticulous examination of the pattern,cytoplasmic and cellular morphology it is possible conclusively to sub characterize MSRCT on histology alone . Our findings are completely based upon histological diagnosis except for few cases of lymphoma which have been confirmed by immunohistochemistry.

Incidence of MSRCT

• Our study includes total of 129 cases of MSRCT in last 10 years which constitute 6.80% of all the brain tumors received in our department.
• Out of the total number of tumor cases (=1897) in our neuropathology department between 1996-2006, Embyonal/Primitive/ Medulloblastoma constituted 4.3% as against 1.8%, lymphomas constituted 0.95% against 3.3%, germ cell tumor 0.42% against 0.6% and metastasis constituted 0.42% against 0.5% of total number of brain tumor.
• Unlike the Western literature where lymphomas form the majority of the cases of MSRCT, we noticed that majority of our cases were embryonal tumors (Medulloblastoma).

Age Incidence

• The maximum number of cases were in the young age group (0-20 yrs) followed by middle age(21-50yrs) constituting 57% and 35% respectively.
• The Mean age group of presentation of MSRCT in the CNS is 23 years in our study, this has not been stated anywhere in Western and Indian literature.
• In our study, majority of cases in the younger age groups were Medulloblastoma and sPNET with few rare cases like pineoblastoma, ependymoblastoma, germ cell tumor and Atypical Teratoid/Rhabdoid Tumor. The mixture of the cases were seen in the middle age group that included medulloblastomas, sPNET,lymphomas and rare ones like pineoblastomas,germ cell tumors and olfactory neuroblastoma.
• MSCRT is supposed to be uncommon in elderly age group(>50yrs) we encountered around 9% of MSRCT in this age group which is higher as compared to 4%-5%.
• Primary CNS lymphomas affected all ages, the peak incidence in our study was in the middle age group (21-40yrs) that was 11/18 cases (61%), followed by elderly and then young age, implying our patient had died before these tumors developed due to severe complications of HIV infection, including opportunistic infection, most commonly Tuberculosis, in INDIA.
• We encountered one case each of adult Atpical Rhabdoid/Teratoid Tumor, Ependymoblastoma and Medulloepithelioma.These tumors are very rare in elderly age group.

Sex Incidence

• In our study M: F was 3:1(96 males against 33 females) indicating higher prevalence in the male.

Location

Of the 129 cases reviewed the most common location of involvement of MSRCT in the CNS is infratentorial accounting to 49% followed by supratentorial, (40%) spinal (9%), scalp (2%) and nasal (1%) respectively.

Radiological correlation

As far as the radiological correlation is concerned we found that radiodiagnosis (CT/MRI) showed excellent correlation with histopathology in medulloblastomas and on a contrary the latter showed maximum discrepancy with Lymphoma, sPNET and Germ cell tumors.

MEDULLOBLASTOMA

Incidence

Medulloblastoma is the most common type of MSRCT encountered in our study. We reviewed a total of 57 cases of Medulloblastoma, this accounted to 44.19% of MSRCT and 3.00% of total number of CNS tumor cases we received in our neuropathology department.

Age and sex distribution

• The overall mean and median age at diagnosis for MBs is 13 years and 11 years respectively, with the peak age of occurrence being around 9 years
• Of the 57 cases of MBs in our study 41 were males and 16 were females (M:F=3-3.5:1).

Location

• Of the total of 57 cases of medulloblastoma 42 were from cerebellar vermis accounting to 73.7%.
• Of the 42 cases 38 were seen in children less than 21 years of age constituting to 90%. Rest of the15 cases showed involvement of cerebellar hemispheres and all these cases were seen in adults.

Radiodiagnosis

• CT/MRI of 52 out of 57 cases (91.23%) of Medulloblastomas showed excellent correlation with histopathological diagnosis.
• About 77.19% of MBs were located in midline in the cerebellum vermis.93% of Medulloblastomas showed marked contrast enhancement in CT scan. 89.47% of MBs were hypointense on pre-gadolinium T1-weighted images. Other associated changes included marked hydrocephalus seen in 59.65% cases. About 3.51% showed areas of hemorrhage and 12.28% showed cystic areas most of them being in adolescent age group and hemispherical in location.

Histopathological Features

• Of the 57 cases of medulloblastoma, classical medulloblastoma contituted 68.42%(39/57cases), desmoplastic 26.32% (15/57 cases) and few cases were of Medulloblastoma with extensive nodularity of 5.26%. (3/57 cases)
• We did not come across any case of large cell anaplastic medulloblastoma and other rare embryonal tumors like melanotic medulloblastoma and medullomyoblastoma.

Primary CNS lymphomas

Incidence

• Of the total of 129 cases of MSRCT we came across 18 cases of CNS lymphomas accounting to 13.95% of MSRCTs in the CNS and 0.95% of total number of CNS tumors received in our department in last 10 years.
• All our cases were immunocompetent, non HIV/AIDS associated cases.
• We did not do EBV correlation.
• We have notice less number of cases of the CNS LYMPHOMAS associated with HIV probably because most of our patient died at a young age due to severe complications of HIV infection, including opportunistic infection, most common of which is Tuberculosis

Age and sex distribution

• Primary CNS lymphomas affect all ages, the peak incidence in our study was in the middle age group (21-40yrs) that was 11/18 cases (61%), followed by elderly and then young age.
• Of the 18 cases of lymphomas 16 were males and 2 were females. (M:F =8: 1 ).

Localization

About 66% of primary CNS lymphomas involve the supratentorial space(12/18cases), including the frontal (5/12), parietal (2/12) lobes, basal ganglia / periventricular regions (3/12) and corpus callosum (1/12), the posterior fossa (3/12), and the spinal cord (3/12). 1 case was having bi-thalamic involvement. Frontal lobe was commonest site for involvement in our study.

Radiodiagnosis

CNSLymphoma is one of the most underdiagnosed tumors on neuroimajing, this could be due to that fact that it mimics any any grade IV tumor. Only 3 out of 18 cases showed radiological correlation accounting to 16.67%.

Histopathological Features

• Of the 18 cases of lymphomas, the diffuse large cell lymphomas was the commonest in our case 14/18 (77.8%), 1 case of lymphoblastic lymphoma. Interestingly we had 3 cases (16.7%) of small cell lymphoplasmacytic lymphoma.
• In only 7 cases immunohistochemistry was done and showed expression of pan – B markers.
• All our 14 cases of large cell Lymphoma showed that diffuse infiltration of brain parenchyma in an angiocentric pattern forming collars of tumor cells within concentric perivascular reticulin deposits. This was one of the major criteria’s besides cell morphology and mitosis which we considered in the diagnosis of large cell Lymphoma.
• We did not come across any case of T-cell lymphomas.
• We came across 3 cases of plasmacytoma in our study and none of which were intracranial. All our cases involned the spinal cord.

SUPRATENTORIAL PRIMITIVE NEUROECTODERMAL TUMORS (sPNET)

Incidence

• Of the total of 129 cases of MSRCT, sPNET were 15 in number i.e. 11.6% of MSRCT and 0.8% of the total number of CNS neoplasms
• This discrepancy could be as the precise statistics of incidence are difficult to determine because of differing viewpoints regarding classification, nomenclature and also due to inadequate sample size i.e. less than 30.

Age and sex distribution

Of the 15 cases the commonest age of presentation was between 0-10 yrs 7/15 (around 45%) followed by 21-30 4/15 around 26%. Of the 15 cases 14 were males and 1 was female.

Localization

These tumors are found in the supratentorially.

Neuroimaging

In all our cases CT / MRI together were effective in diagnosing sPNET in around 26.67% of cases i.e only 4 out of 15 cases,as this is a recently categorised entity by WHO. Hence, the need for clinicians and radiologists to note the difference in the imaging criteria’s.

Histopathology

Light microscopic features of cerebral suprasellar PNETs are basically similar to medulloblastoma.

PINEOBLASTOMA

Incidence

In our study we received 7 cases of Pineoblastomas of 129 MSRCT accounting to 5.4% of MSRCT and 0.4% of total number of CNS neoplasms.

Age and sex distribution

• We came across patients with age groups ranging from 6 months to 40 years with the mean age of 21 years with a peak between 12-20 years.
• Of the 7 cases reviewed in our study were 4 males and 3 females hereby indicating slight male preponderance.

Neuroimaging

In all our cases CT/MRI could diagnose pineoblastoma preoperatively. This was possible as these tumors are typically pineal location and are large lobulated, poorly demarcated, homogeneous mass, that is hyperdense after contrast enhancement. On T1 weighted MRI scan, pineoblastomas the hypo-to-isointense but are heterogeneous upon contrast administration.

Histopathology

All our cases of Pineoblastomas were highly cellular neoplasms composed of patternless sheets of densely packed small cells with round to irregular nuclei and scant cytoplasm. Pineocytomatous rosettes were lacking in all our case, although Homer-Wright and Flexner-Wintersteiner rosettes were seen in few.

CNS GERM CELL TUMORS

Incidence

In our study we received 8 cases of Germ cell tumor of 129 MSRCT accounting to 6.2% of MSRCT and 0.4% of total number of CNS neoplasms

Age and Sex distribution

• We came across patients with age groups ranging from 1 year to 31 years with the mean age of 20 years with a peak at 10 years
• Of the 8 cases we studied, there were 5 males and 3 females thereby indicating slight male preponderance.
• In our study the entire pineal region germ cell tumor were seen in males (3/3) and majority of suprasellar germ cell tumors are encountered in females (Male to female 1: 3).

Localization

In noted that all our cases of Germ cell Tumor were midline in location. Out of the 8 cases of germ cell tumor 7 were above the third ventricle and 1 below it [4 suprasellar, 3 pineal and 1 posterior fossa], i.e. 87.5% of tumors were above third ventricle.

Neuroimaging

Radiological diagnosis of germ cell tumors in our study was made only in 2 out of 8 cases which account to be 25% only (low specificity). This is due to the fact that the neuroradiological profiles of CNS germ cell tumors are largely non-specific, and definitive histological subclassification requires tissue examination.

Histopathology

Germinoma / dysgerminoma, embryonal carcinoma, and Yolk sac tumor are considered here as they form differential of MSRCT.

OLFACTORY NEUROBLASTOMA

Incidence, age and sex distribution

In our study we came across 4 cases of olfactory neuroblastoma accounting to 3.1% of MSRCT and 0.2% of total number of CNS tumors referred to our department in last 10 years.

The age of those affected ranges from 20 to 60 years

We noted a bimodal age distribution, with cases tending to cluster around ages 20 and 50 years with Male:Female=1:1

Localization

All our cases of Olfactory neurobastoma involved the cribrirform plate.1 of our case showed infiltration of adjacent structures involving the paranasal sinuses, oro-nasopharynx, the base of skull, and even the cerebral frontal lobes.

MEDULLOEPITHELIOMA

Age and Sex Distribution 

• We came across 2 cases of these tumors in the age group of 41 to 50 years. Though this entity has not been reported in this age group, review of this tumor by 3 pathologists confirmed the diagnosis as they showed a very typical histopathological appearance resembling neural tubes. (Case No-V961,V990:Photograph).
• Of our 2 cases 1 was male and the other was female.

Location 

We found 1 case in suprasellar and the other in spinal location.

CT/MRI scan

Variable and non specific. No correlation was made out in our cases.

Histopathological

Both the tumors had a very typical cytoarchitecture closely resembling embryonic or primitive neural tube.They were characterized by papillary, tubular and trabecular arrangements of the neoplastic pseudostratified neuroepithelium, having a external limiting membrane resting on a delicate reticulin framework. Mitoses were abundant and tend to be located more on the non-ciliated, reticulin-free luminal surface.

EPENDYMOBLASTOMA

Age and sex distribution

We came across 2 cases (10 months and 25 years) of ependymoblastoma in our 10 year study. The late presentation in 1 of our case could be due the non specific symptoms Both our cases were females.

Localization

Both our cases were large and located supratentorially

Histopathology

Diagnostic features were those of a central primitive neuroectodermal tumor with distinctive multilayed rosettes, with cells in the outer rim of the rosette merging with the surrounding undifferentiated neuroectodermal cells. The chief histological characteristic of ependymoblastoma was the dense cellularity with distinctive and numerous rosettes. These rosettes were multi-layered and form concentric cellular rings around small round lumina

AYPICAL TERATOID / RHABDOID TUMOR (AT/RT)

Incidence

We came across 2 cases (0.1%) of ATRT in last 10 years. Accurate data relative to incidence are difficult to obtain since this tumor has been generally misdiagnosed until the past few years.

Age and sex distribution

Of the 2 cases observed in last 10 year 1 was an infant of 3 months female and 1 case of 54 years male.

Localization

Both of our cases were supratentorial in location.

Neuroimaging

Neither CT nor MRI was useful in our case. Findings on both computerized tomography (CT) and magnetic resonance imaging (MRI) are similar to those seen in patients with medulloblastoma.

Histopathology

These were the tumors containing rhabdoid cells, with additional, variable components of primitive neuroectodermal, mesenchymal and epithelial cells.

MALIGNANT MELANOMA

• Of the 129 cases of MSRCT we came across 1 case (26 years Male) of Malignant Melanoma constituting to 0.1% of all CNS tumors received in our department in last 10 years.
• Our case showed considerable pleomorphism with large and bizarre tumor cells including multinucleated giant cells and a variable amount of melanin pigment.

ANAPLASTIC OLIGODENDROGLIOMA

·       Of the 129 cases of MSRCT we came across 1 case (26 year Male) of Recurrent Anaplastic Oligodendroglioma constituting to 0.1% of all CNS tumors received in our department in last 10 years

·       We have included Anaplastic Oligodendrogliomas in the category of MSRCT as the biopsy showed a highly cellular small cell tumor showing marked cytological atypia with high mitotic activity simulating MSRCT, in addition it also showed vascular proliferation with foci of necrosis

METASTATIC TUMORS OF THE CNS

·       Of the 129 cases of MSRCT we came across 8 cases of metastasis accounting to 6.2% of all CNS tumors received in our department in last 10 years.

·       6 out of 8 cases were more than 40 years of age.

·       The male: female ratio for cerebral metastasis in our case was 1.67:1 (5 males and 3 females).

·       7 of our cases had cerebral metastasis and 1 had intraspinal metastasis (14 year male).

·       Under this category we have included only those cases of metastasis which did not show any squamous or adenomatous differentiation and showed histological picture simulating MSRCT’S.

·       The distribution of metastasis to the brain in our cases was as follows oat cell carcinoma of Lung (1 case 50 years male), carcinoma Prostate (1 case 61 years male), Germ cell tumor (1 case 14 years male), undifferentiated carcinoma (52 years male) and 3 cases (1 male and 3 female) were kept under broad category of MSRCT.

MIMICS OF MSRCT

Includes

·       Central Neurocytomas, Paragangliomas and Pineocytomas as they are composed of small cells without any differentiation.

·       Ganglioglioma, Gangliocytoma and DIG component is composed of small cells with focal ganglio-neuronal differentiation.

Importance

·       Mimics form grade 1 tumors with excellent prognosis in contrast to MSRCT which are grade 4 neoplasms.

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