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    Open AcceMethodology The role of immunohistochemistry in medullomyoblastoma – a case series highlighting divergent differentiation Man Updesh S Sachdeva1, Mahesha Vankalakunti1, Aruna Rangan1, Bishan D Radotra1, Rajesh Chhabra2 and Rakesh K Vasishta*1

    Address: 1Department of Histopathology, Postgraduate Institute of Medical Education & Research, Chandigarh, India and 2Department of Neurosurgery, Postgraduate Institute of Medical Education & Research, Chandigarh, India

    Email: Man Updesh S Sachdeva - drmanupdeshpgi@yahoo.co.in; Mahesha Vankalakunti - vkmahesh123@yahoo.co.in; Aruna Rangan - rangan.aruna@gmail.com; Bishan D Radotra - bishanradotra@hotmail.com; Rajesh Chhabra - rajeshchhabra@gmail.com; Rakesh K Vasishta* - r_vasishta@yahoo.com

    * Corresponding author

    Abstract Aims: To analyse the histo-morphology of cases of medullomyoblastoma and identifying its divergent differentiation.

    Methods: A retrospective review of all cases reported as medulloblastoma between the period of Jan 2000 to Dec 2006 was carried out on Hematoxylin and eosin (H & E) stained slides. The cases were screened on light microscopy for primitive neuroectodermal component of a medulloblastoma accompanied by areas of "myoid" differentiation, identified on the basis of presence of strap cells (indicating a clear skeletal muscle differentiation) and/or large anaplastic cells with vescicular nuclei and moderate to abundant amount of eosinophilic cytoplasm. All these cases were subjected to a panel of immunohistochemical stains, including Desmin, GFAP, NFP, HMB45, SMA, S100, CK and EMA. Ultrastructral analysis was done on tissue obtained from paraffin blocks in 2 cases.

    Results: Male predominance (M:F = 5:1) was noted with an incidence of five percent of all cases of medulloblastoma (6 out of 120 cases) over a period of 6 years. Primitive neuroectodermal areas were accompanied with areas of "myoid" differentiation, 5 cases showing strap cells. Two cases with epithelial and cartilaginous differentiation were seen. Three cases showed focal melanocytic differentiation, identified only on HMB45 immunostaining. Four cases showed glial differentiation. Neuronal differentiation again was very focally seen in two cases, of which one was identified only by NFP immunostain. Seventh case is included in the study, however it is not considered to calculate incidence as it occurred beyond the period of 6 years of records search.

    Conclusion: Medullomyoblastoma is a rare childhood tumor of cerebellum. Majority of cases reveal divergent differentiation, which are identified with the help of panel of immunostains indicating multi-potential nature of primitive neuroectodermal cells.

    Published: 25 April 2008

    Diagnostic Pathology 2008, 3:18 doi:10.1186/1746-1596-3-18

    Received: 14 February 2008 Accepted: 25 April 2008

    This article is available from: http://www.diagnosticpathology.org/content/3/1/18

    © 2008 Sachdeva et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Diagnostic Pathology 2008, 3:18 http://www.diagnosticpathology.org/content/3/1/18

    Introduction Medullomyoblastoma (MMB) is a rare cerebellar embryo- nal neoplasm that occurs almost exclusively in children. It has a biphasic histo-morphology, containing myoblastic and primitive neuroectodermal components. MMB arises exclusively in the cerebellum. English literature provides some case reports of this rare tumor and an occasional series of small number of cases [1-11]. In the present series, we present histo-morphological features of 7 cases of medullomyoblastoma and try to find out any divergent differentiation by using a panel of immunostains.

    Materials and methods A retrospective review of all cases reported as medullob- lastoma over the period of 6 years in the department of Histopathology, Post graduate Institute of Medical Educa- tion and Research (PGIMER), Chandigarh, was carried out. Hematoxylin and eosin (H & E) stained slides as well as paraffin blocks of all these cases were available as archi- val material in the department. H & E slides were screened for cases showing primitive neuroectodermal component of a medulloblastoma accompanied by areas of "myoid" differentiation, identified on the basis of presence of strap cells (indicating a clear skeletal muscle differentiation) and/or large anaplastic cells with vescicular nuclei and moderate to abundant amount of eosinophilic cytoplasm. Morphological details on H & E stained slides of the selected cases were carefully noted, with a special mention to any other differentiations accompanying the two com- ponents of primitive neuroectodermal and rhabdomyob- lastic cells. Sections from paraffin embedded tissues of all these cases were subjected to a panel of immunohisto- chemical stains, namely, Desmin, GFAP (Glial Fibrillary

    Acidic Protein), NFP (Neurofilament Protein), HMB45, SMA (Smooth Muscle Actin), S100, CK (Cytokeratin) and EMA (Epithelial Membrane Antigen). Ultrastructural analysis was done on tissue obtained from paraffin blocks in 2 cases.

    Results A total of 120 cases of medulloblastoma were present in the retrospective search of files over the period of 6 years. A retrospective review of H & E stained slides showed 6 cases (5% of all medulloblastomas) which had morpho- logical evidence of "myoid" differentiation accompanying the typical areas of primitive neuroectodermal cells. Three of these cases had been reported as medullomyoblastoma during routine reporting. The clinicopathological data of these cases have been summarized in Table 1. The case no. 7 that is included in the Table 1, was a previously diag- nosed case of medullomyoblastoma, confirmed on ultrastructural analysis in the year 1993. However this case is beyond the period of 6 years of records search. This case was also subjected to same panel of immunhisto- chemical stains.

    Clinical characteristics The patients ranged in age from 3 to 28 years (median age – 6 years). Six patients were male and one was female. The most common presentations were headache and vomit- ing, followed by altered sensorium, ataxia and vertigo (Table 1). In all patients, imaging revealed a posterior fossa space occupying lesion (SOL), involving the cerebel- lum.

    Table 1: Clinical data and histology of Medullomyoblastoma

    Case No. Age#/Sex Presentation Duration of symptoms

    (days)

    Imaging (CT/ MRI)

    Histopathological features

    1 28 y/M Headache, vomiting, ataxic gait

    14 Posterior fossa SOL Predominant areas of PNE cells, nodules of cells showing smooth muscle differentiation, cartilaginous islands

    2 6 mon/F Vomiting, altered sensorium

    15 Posterior fossa SOL, hydrocephalus

    Predominant areas of PNE cells, RMB areas present, focal cartilaginous and epithelial differentiation

    3 4 y/M Recurrent headache, vomiting

    20 Posterior fossa contrast enhancing SOL

    Co-dominant RMB and PNE areas, many strap cells present

    4 3 y/M Headache, vomiting, altered sensorium

    20 Posterior fossa SOL Predominant areas of PNE cells, RMB areas present with strap cells

    5 4 y/M Persistant vomiting 60 Posterior fossa SOL, hydrocephalus

    Predominant areas of PNE cells, RMB areas with strap cells present

    6 8 y/M Headache, vomiting, vertigo

    60 Posterior fossa SOL Predominant areas comprise of larger atypical cells with vesicular nuclei and moderate amount of cytoplasm, no typical strap cells present, rest of the areas show PNE cells

    7 4 y/M Vomiting, altered sensorium

    30 Posterior fossa SOL Predominant areas of PNE cells, RMB areas show strap cells

    PNE – Primitive neuroectodermal; RMB – Rhabdomyoblastic; SOL – Space occupying lesion; Age# y – years & mon-months

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  • Diagnostic Pathology 2008, 3:18 http://www.diagnosticpathology.org/content/3/1/18

    Pathology At low power morphological features in all cases showed undifferentiated areas comprising of primitive neuroecto- dermal cells. These areas did not reveal definite rosette for- mation in any of the 7 cases. All the cases except Case 6 [Table 1] had interspersed hypocellular areas which on higher magnification showed features of rhabdomyoblas- tic differentiation. The cells with "myoid" differentiation had large eccentrically placed vescicular nuclei and mod- erate amount of eosinophilic cytoplasm. Strap cells, con- sidered to be the best morphological indicator of skeletal muscle differentiation, were seen in all cases, except Case 1 and 6 [Table 1]. The areas with rhabdomyoblastic differ- entiation comprised of 20 to 50% of total tumor tissue.

    Case 1 [Table 1] was an extremely rare case of medullomy- oblastoma in adult patient, aged 28 years. On histopatho- logical examination, the tumor predominantly had nodules of primitive neuroectodermal cells with areas of necrosis. Another prominent finding was presence of mul- tiple islands of cartilage located in the centre of the prim- itive neuroectodermal nodules [Fig 1A]. Some of these nodule