International Journal of Oral & Maxillofacial Pathology. 2013;4(2):24-33 ISSN 2231 – 2250

Available online at http://www.journalgateway.com or www.ijomp.org

Review Article

Small Round Cell Tumor of the Head and Neck Region: A Review

Reshma V, Kavita Rao, Priya NS, Umadevi HS, Mohsin G, Sreelatha Hosthor

Abstract

Small round cell tumors configure a heterogeneous group of malignant neoplasms that present clinical predominance in children and young adults. It encompasses a wide variety of
undifferentiated primitive neoplasms which have in common the ability, with varying frequency, to present as a nondescript proliferation of round cells with high nuclear cytoplasmic ratio and
hyperchromatic nuclei by light microscopy. Their differential diagnosis is influenced by the age of
the patient, their site of occurrence, and slight degrees of differentiation exemplified by minor architectural and cytoplasmic features. All tumour types have special treatment modalities and the prognosis is dependent on the exact histological diagnosis confirmed by adjuvants like immunohistochemistry and cytogenetics. This article reviews some of the most common small round cell tumors involving the head and neck region which includes Ewing’s sarcoma, rhabdomyosarcoma, neuroblastoma, and lymphomas.

Keywords: Cytogenetics; Head Neck; Immunohistochemistry; Small Round Cell; Undifferentiated

Tumors.

Reshma V, Kavita Rao, Priya NS, Umadevi HS, Mohsin G, Sreelatha Hosthor. Small Round Cell Tumor of the Head and Neck Region: A Review. International Journal of Oral & Maxillofacial Pathology; 2013:4(2):24-

33. ©International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta

Software Private Limited. All Rights Reserved.

Received on: 27/04/2013 Accepted on: 09/08/2013

Introduction

Small-round-cell tumors (SRCTs) are a group of cytomorphologically similar
neoplasms with varied origin. The neoplastic
elements include undifferentiated, uniform, small round to oval closely packed cells with a solitary hyperchromatic nucleus and a high nuclear cytoplasmic ratio. The nucleoli may
or may not be prominent.1,2
They lack any particular morphological features that would allow precise identification and represent a diagnostic challenge when examined by light microscopy alone. Thus their diagnosis requires an integrated approach which includes immunophenotypic and genetic
analysis.3 Immunohistochemistry is now successfully integrated into the diagnostic routine, as they give valuable
complementary information.4 SRCTs occur
mostly in children and young adults. They tend to involve the skeletal system or soft tissue.3
The most common neoplasms capable of presenting as a SRCT are Ewing's family of tumors, rhabdomyosarcoma, neuroblastoma, lymphomas, and desmoplastic small round cell tumor
(DSRCT).2,5,6,7 DSRCT is predominantly an intra-abdominal tumor which sometimes
includes pleura and tunica vaginalis.3 The
present article selectively reviews the salient histopathological, immunohistochemical and cytogenetic features of small round cell tumors in the head and neck region.

Ewing’s sarcoma Family of Tumors

(ESFTs)

ESFTs are those group of highly malignant
SRCTs which are characterized by phenotyphic heterogeneity i.e. lack of overt differentiation along a single pathway, non- specific histotypic markers or complex patterns of multi-lineage differentiation with co-expression of neural, mesenchymal and
epithelial traits.8 ESFTs comprise osseous and extra osseous Ewing’s sarcoma (ES), peripheral primitive neuroectodermal tumor
(pPNET), and Askin tumor of the thorax.
Roessner et al classified them into three subgroups, namely typical Ewing’s sarcoma (TES), atypical Ewing’s sarcoma and peripheral neuroectodermal tumor (PNET).9
ES and PNET are closely related tumors with the same t(11:22)(q24;q12) translocation. They represent opposite ends of ES family of tumors that ranges from undifferentiated neoplasms (ES) to morphological evidence of neural
differentiation (PNET).10 In the Intergroup
Ewing’s Sarcoma Study (IESS)
approximately 4% of the primary bone tumors arose in the bones of the head and neck.11 Bone and soft tissue EFTs in the

©2013 International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved

ISSN 2231 – 2250 Small Round Cell Tumor of the... 25

head and neck have been reported to represent anywhere from 1–7% of EFTs in some studies.13

Histopathology: Conventional: The bone marrow is filled with monotonous population of round blue cells that acquire a nested, sheet-like or solid pattern without any intervening stroma (Fig 1). As the tumour invades soft tissues or periosteum, the stroma consists of reticular network and abundant vasculature and presents a filigree pattern (lace-like rest of tumoral cells enveloped in a dense fibrillar matrix). It shows three types of cells with transitional forms between them:

a) Principal / tumoral cells: small blue round cells, cell contours are less defined with scarce cytoplasm.
b) Dark cells: condensed chromatin and
scarce cytoplasm conforming apoptotic figures.
c) Clear cells with poorly defined cytoplasmic borders filled with abundant amounts of glycogen which is
considered a specific marker.14,15
Vessels with hyalinised walls, surrounded by a rim of neoplastic cells are associated with necrosis which may be focal or extensive. Inflammatory cells are usually absent. Parallel rims of reactive bone consisting of osteoblasts, chondroblasts and giant osteoclasts are seen deposited in onion skin lamellar pattern.

Atypical: As compared to conventional ES, the cells are larger in size (20-24µm) and heterogeneous in morphology with better delimited cell contours. The cells consist of eosinophilic cytoplasm with irregular,

grooved nuclei. 14,15

PNET or ES with neuroectodermal differentiation:14 Morphological features are similar to conventional ES with at least one

third of the tumor showing Homer-Wright rosettes or pseudorosettes (includes a group
of six to ten cells oriented towards a central
core filled with fibrillar material). The nuclei of cells is round or elongated with condensed chromatin. In another pattern, a fibrillary background which may adopt a lobulated configuration intermingled with less densely packed cell population may be seen. Nests of tumoral cells remain within the collagen bundles.

Immunohistochemistry: Both ES and

PNET express the membrane antigen
p30/32MIC2/HBA71/CD99 or 12E7/O13; a MIC2 gene product. P30/32 and 12E7 are different epitopes on MIC2 gene product. Although, CD99 is not specific for ES/PNET (expressed even by lymphoblastic leukemias, weakly by alveolar rhabdomyosarcoma etc), combination with other markers like Friend Leukemia Integration 1 Transcription Factor (FLI1) - a gene product belonging to E-twenty six (ETS) trascription factor, Human Natural Killer 1 (HNK1)- a neuronally expressed adhesion molecule and caveolin-1 a product of a gene CAV 1 that encodes slowly inactivating L-type voltage-dependent calcium channel in skeletal muscle cells, gives more accurate diagnosis and helps to avoid erroneous diagnosis. Neuronal markers like neuron-specific-enolase, S-100, etc are positive in PNET but the cells are negative for chromogranin and
synaptophysin.14,16,17

Cytogenetics: Translocation, t(11;22) (q24;q12) i.e., fusion between the 5’end of the EWS gene from chromosome band

22q12 with the 3’ portion of the 11q24 FLI1 gene is seen. This EWS/ETS fusion protein blocks the differentiation of pluripotent marrow stromal cells. Rest 10-15% of the cases have t(21;22) (q22;q12) fusing EWS
to a closely related ETS gene.16

Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is composed of neoplastic mesenchymal cells showing
varying degrees of striated muscle cell
differentiation. It accounts for about 5% to
10% of all childhood malignancies.18 Head and neck RMS when compared to other
parts of the body have a distinct prognostic and biologic behaviour. They are
anatomically divided into two categories:
Parameningeal -- consisting of RMS of nose, nasopharynx, paranasal sinuses, middle ear, mastoid, infratemporal fossa and pterygopalatine fossa. Non-parameningeal -- consisting of RMS of the scalp, orbit, parotid
gland, oral cavity, oropharynx and larynx.18
Horn and Enterline (1958) described four histologic subtypes of RMS: Pleomorphic, Embryonal, Alveolar and Botryoid types. Only embryonal RMS (generally seen in children) and alveolar RMS (common in adults) belong to the family of small round
cell tumors.10
The intergroup rhabdomyosarcoma studies have shown that in head and neck region
71% of tumors were of embryonal type and

26 Reshma V, et al. ISSN 2231 - 2250

13% of alveolar type.19 According to a study by J. Hicksa and C. Flaitz, primary head and neck rhabdomyosarcomas occur in 35% of children.20

Embryonal Rhabdomyosarcoma: (E-RMS) According to the World Health Organization, E-RMS is “a variant of rhabdomyosarcoma featuring sheets of primitive round and differentiating rhabdomyoblasts admixed in

various proportions”.10 (Fig 2) This lesion is named for its remarkable resemblance to
developing muscle in embryos and foetus. Just as embryonal skeletal musculature
appears to condense out of a primordial soup of gelatinous matrix and primitive
mesenchyme, so is embryonal
rhabdomyosarcoma and is typified by alternating areas of cellular condensation and laxity.21 The tumor cells vary from being
small undifferentiated round or spindle shaped cells to number of differentiated cells with eosinophilic cytoplasm characteristic of rhabomyoblasts floating in a sea of primitive mucous ground substance. Cross-striations
are discernible in 50–60% of cases.1,21
The tumor cells vary from being small undifferentiated round or spindle shaped cells to number of differentiated cells with eosinophilic cytoplasm characteristic of rhabomyoblasts floating in a sea of primitive mucous ground substance. Cross-striations
are discernible in 50–60% of cases.1,21

Alveolar rhabdomyosarcoma: (A-RMS) Most of these tumors are composed of round cells with scanty cytoplasm and nuclei that is uniform in size and shape with coarse chromatin. Sometimes it consists of one or two prominent nuclear folds. Nuclear necrosis and pyknosis with high mitotic

activity is usually observed.10 A-RMS usually consists of two patterns:
1. Classic: Are highly cellular, poorly differentiated, and aggressive-appearing
lesions that typically form nests separated by a prominent framework of
fibrovascular septa. From this fibrous
buttress hang rows of tumor cells, with loss of tumor cell cohesion in the periphery of the alveolar nests and increased cohesion in their central
portions. 10,21
2. Solid: These variants show crowded, highly cellular, undifferentiated round cell without fibrovascular septa. Solid alveolar rhabdomyosarcomas have biological features and clinical behaviour
identical to those of typical alveolar rhabdomyosarcomas.21

Immunohistochemistry: Cells are positive for desmin and muscle-specific actin. A more sensitive maker for this tumor is MAB

5.8A, which recognizes the MyoD1 gene product. MYoD1 is a DNA-binding phosphoprotein that binds to the enhancer sequence of muscle-specific genes, regulating their transcription. Another specific marker is myogenin which is detected at the early stage of myogenic
differentiation.22

Cytogenetics: Alveolar RMS shows t(2;13)(q35;q14) translocation. The genes involved are PAX3 (paired box gene) on chromosome 2 and FKHR (Forkhead domain) on chromosome13. Embryonal RMS are usually hyper-diploid and do not show t(2;13). There is loss of heterozygosity for 11p15 region. The neoplasms have extra

copies of chromosome 2,8,9,11,12 and 13.8

Olfactory Neuroblastoma

Primary pediatric head and neck
Neuroblastoma is rare, with metastatic disease being the more common mode of involvement in this anatomic region.25
Esthesino neuroblastoma (ENB) or Olfactory neuroblastoma is an uncommon malignant neoplasm of the nasal vault which was first described in 1924, in French literature. ENB represents about 5% of all nasal malignant
tumors.24
Skolnik et al. were able to find only about
100 reported cases in the world literature up to the year 1966. More recently, Broich and colleagues have found about 1000 new cases of ENB being reported.25 According to
a study, the mean age at presentation was
53 years, (range: 40-70years) with a moderate male predominance (male:female ratio being 55:45).47

Histopathology: ENB is thought to originate from basal cells of olfactory epithelium which express neural cell adhesion molecule and the mammalian homologue of Drosophila-

achaete-scute (MASH) gene.25 Cantrell et al described characteristics of ENB as a lesion
which is compartmentalized into lobules by
slender vascular fibrous septa. The lobules contain cells with almost nonexistent cytoplasm, round nuclei with sharply defined chromatin and plexiform intercellular fibrils. True rosettes/ Flexner-Wintersteiner rosettes (consists of spaces lined by columnar cells

ISSN 2231 – 2250 Small Round Cell Tumor of the... 27

with nuclei oriented radially around the space) and pseudorosettes / Homer Wright rosettes are seen (Fig 3). Cytoplasm shows secretory granules similar to catecholamine
granules.24,25 Robert et al classified this tumor into three different types considering
its clinical and histopathological appearance:

1. Pattern I: A tumor with sheets of small, round cell separated by connective tissues septa; pseudorosettes or Homer Wright rosettes are seen.

2. Pattern II: Consists of cells with round to oval nuclei with clear nuclear membranes, scanty cytoplasm and indistinct cell borders. True rosettes or Flexner-Wintersteiner are seen.

3. Pattern III: Pattern similar to neuroblastoma with production of neuropil, a wispy, light pink, fibrillar material produced by undifferentiated neuroblasts. Rosettes are seen with abundant haemorrhage, fibrosis and hemosiderin deposition. Clusters of lymphocytes and islands of dystrophic

calcification are seen.24

Immunohistochemistry: The cells are positive for neuron specific enolase and neural filament protein. S-100 and vimentin

are positive in sustentacular cells.22

Cytogenetics: In nineteenth century, ENB tumours were found to express HASH, the human homologue of the MASH gene. The demonstration by RT-PCR of HASH gene expression, although still investigational, could become the diagnostic procedure of

choice to detect ENBs.25

Malignant Lymphomas

Lymphomas are the heterogeneous group of clonal malignant disease that share the single characteristic of arising as the result
of somatic mutation in a lymphocyte
progenitor. A lymphoma may arise in lymph nodes or any organ, either by spread from lymphatic sites or as a manifestation of primary extranodal disease.26 According to
studies done by Pecorari et al and Eisenbud et al, Lymphomas are the third most frequent malignant tumor of the maxillofacial region following squamous cell carcinoma and salivary gland neoplasms. According to Epstein et al it is the second most common
malignant disease in the oral region.27 Most of the head and neck lymphomas are of B- cell origin.28 Traditionally, the lymphomas are
divided into Hodgkin’s (HL) - shows
presence of Reed-Sternberg cells and Non- Hodgkin’s lymphomas (NHL) - no Reed Sternberg cells are seen because of their difference in histology and pattern of
behaviour.27,29

Non-Hodgkin’s lymphoma

NHLs are much less predictable than
Hodgkin’s disease and have a far greater predilection to disseminate to extra nodal tissues.27 Lymphomas account for 50% to
59% of the head and neck malignant
neoplasms in children. A decided majority of non-Hodgkin’s lymphomas arise in lymph nodes, 24% of these malignancies arise in extra nodal sites. Lymphomas arising within the oral cavity accounts for less than 5% of all oral malignancies and approximately 85% of the lesions involve the tonsils and
palate.29 To date, only 12 cases of the non- Hodgkin’s lymphoma of the tongue has been mentioned in the literature.30 Diffuse large
lymphomas is most frequently encountered type27 and comprised of 50% of oral lymphomas in one series of study.26
The frequent lymphomas occurring in nasopharynx and Waldeyer’s ring are small B-cell lymphomas such as small lymphocytic lymphoma, mantle cell lymphoma, natural killer (NK)/T cell lymphomas and follicular lymphoma. In salivary glands, mucosa associated lymphoid tissue (MALT) lymphomas are common. The other types include plasmablastic lymphoma and
Burkett’s lymphoma.31 In a study, diffuse large cell lymphoma (Fig 4) was diagnosed
in 38% and small cell lymphoma in 27.4% of cases. The rest of the cases include
plasmacytoma, Immunoblastic lymphomas and Burkett’s lymphoma.29 Increasing number of HIV cases present with oral lymphomas especially plasmablastic lymphomas.31,32 Some of the features of commonly found NHL in head and neck region along with IHC and cytogenetic
features are elicited in Table 1.

Hodgkin’s Lymphoma (HL):

Characterized histologically by infiltration of the involved organ with Reed-Sternberg or
Hodgkin’s cells in an appropriate cellular
background.34
Hodgkin’s cells:37 Neoplastic large ovoid cells with indistinct cell borders, indented vesicular nucleus with thick nuclear membrane and huge hyperchromatic intensely acidophilic nucleolus.

28 Reshma V, et al. ISSN 2231 - 2250

Reed-Sternberg cell: (RS cells): Large cell with two or more often mirror-image nuclei, each containing a single prominent nucleolus. The nucleoli are typically large and round and often resemble inclusion bodies. Chromatin is usually condensed at
the nuclear membrane, giving rise to a thickened nuclear border and a clear halo- like space around the nucleolus. The cytoplasm is abundant and slightly
eosinophilic.42

Sl

no

Tumor

Histopathology

Immunohisto

chemistry

Cytogenetics

1.

Diffuse large B cell lymphoma

Large irregular or lobated nuclei, size equal to or exceeding the nuclei of normal macrophage with scant cytoplasm. Two types:

A. Germinal centre like DLBCL.

B. Activated peripheral blood B-cell type33

Positive for CD20, CD45 and monotypic Ig.

Positive for CD20, CD 10, BCL 6

t(14;18)(q32;2)

Trisomy gains of

3q, 18q21-q22 and loss of 6q21-

22. Increased expression of NF

2.

Small lymphocytic lymphoma

(SLL)

Proliferation of non-activated, mature looking small lymphocytes selectively involving the interfollicular regions or B-zones of the node. The para-immunoblasts and pro-lymphocytes are hallmark of SLL. 34

CD 20 +ve, weak monotypic surface Ig. Ki 67 index is

low

Deletions of

13q14.

3

Follicular lymphoma

Nodular growth of monotonous cells. Three types: 1.

Contains small cells (size of normal lymphocyte) 2. Has large cells (2 to 3 times the size of normal lymphocyte, resembles mitotically active germinal centre cell) 3. Intermediate (contains both small and large lymphocytic cells). Internodular and intercellular reticulin is more

abundant. 35-37

CD19, CD20, CD10, BCL-2 positive.

t(14;18)(q32;q2)

4.

Mantle cell lymphoma

Medium to large sized monomorphic round neoplastic cells, arranged in diffuse or nodular pattern, hyalinised small blood vessels, and scattered epithelioid cells. 31

Positive for CD5,

CD20, CD43, BCL

1, negative for

CD10, BCL 6

t(11;14)(q13;q32). Increased cyclin D1 expression.

4.

Plasma cell neoplasias

Three types: Multiple myeloma (multiple bones involved), solitary bone plasmacytoma, and extramedullary plasmacytoma. Shows proliferation of

mature and immature plasma cell (eccentrically placed nuclei with cartwheel appearance), bone marrow plasmacytosis, osteolytic lesions, M-protein in serum, and Bence-Jones protein in urine. 38,39

To identify monoclonal immune-globulins i.e., Ig G, lambda, Ig kappa.

t(8;14), t(2;8) or t(8;22), translocation between myc and IgH.

5.

Burkitt’s

lymphoma

Three variants:

1. Endemic: refers to Burkitt’s occurring in African

children. Epsten Barr Virus (EBV) + in all most all cases.

2. Sporadic: Occurs in all geographic areas. EBV + in

15%-30% of cases.

3. Immunodifficiency associated: Common in HIV+

patients. May show plasmacytoid differentiation. Uniform or slightly pleomorphic medium sized cells,

moderate amount of cytoplasm, squaring off edges between the neighbouring cells, starry sky pattern due

to admixed tingible body macrophages, high mitotic rate and necrosis. 37,40

Positive for CD

20, CD10, Monotypic Ig

80% with t(8;14) translocation, 20% t(2;8) or t(8;22)

6.

MALT

lymphoma

Observed in salivary glands, thyroid, stomach etc, originate from marginal zone B cells, shows cellular heterogeneity with monocytoid B cells, small

lymphocytes, plasma cells, and occasionally large lymphocytes.

Two variants:

1. Few cases show prominent follicular growth pattern resulting from follicular colonization, absence of lymphoepithelial lesions, centrocyte-like (CCL) cells representing minimal plasma cell differentiation (follicular growth type).

2. Few cases show marginal zone distribution pattern of CCL cells, presence of colonized follicles lymphoepithelial lesions and plasma cells.41

Positive for CD20, and surface Ig D. Negative for CD10, CD5

Trisomy 3, t(11;18) (q21;q21),27-32 t(1;14) (p22;q32),33 and t(14;18) (q32;q21). 34.49

7.

NK/T cell lymphoma

Tissue densely populated by abnormal lymphocytes (small, intermediate and large), areas of necrosis and angiocentric and angiodestructive growth pattern.34

CD56 +ve and

CD2 +ve. Absence of surface CD3 but presence of cytoplasmic CD3.

Lack of TCR genes rearrangements.

8.

Plasmablast ic lymphoma

Found in HIV infected patients, diffuse infiltration of large neoplastic cells in the oral submucosa with eccentrically placed nuclei and paranuclear hof,

CD 4-ve, and CD2-ve. VS38c + ve and CD79a

ISSN 2231 – 2250 Small Round Cell Tumor of the... 29

interspersed with tingible body macrophages. High

proliferative and mitotic activity, apoptotic figures, and single cell necrosis seen.32

+ve.

Table 1: Features of NHL (DLBCL: Diffuse large B-Cell lymphoma, CD: Cluster of Differentiation, NF: Neurofilament, BCL: B-Cell lymphoma, EBV: Epstein-Barr Virus, MALT: Mucosa associated
lymphoid tissue, TCR: T-cell receptor, HIV: Human Immunodeficiency virus, LMP: Latent membrane protein, SLL: Small lymphocytic lymphoma, CCL: Centrocyte-like)

Sl No

Small round cell

tumor

Immunohistochemistry

Cytogenetics

1.

Ewing’s sarcoma

Family of Tumors

P30/32 and 12E7 along with FLI1, HNK, and CAV1

1. t(11;22)(q24;q12) 2. t(21;22) (q22;q12):

10-15% of cases

2.

Rhabdomyosarcoma

MAB 5.8, myogenin

1.t(2;13)(q35;q14)

2.Loss of heterozygosity for 11p15 region

3.extra copies of 2,8,9,11,12 and 13

3.

Olfactory

Neuroblastoma

NSE, NF, S-100

Express HASH gene

4.

Non-Hodgkin’s

Lymphoma

Summarized in table 1

Summarized in table1

5.

Hodgkin’s lymphoma

H-RS positive for CD30, CD15, CD40

Gains of 2p, 9p, 16p, 17q, 19q, 20q, and losses of 6q, 11q, and 13q.

Table 2: Summary of immunohistochemical and Cytogenetic feature of SRCTs

Sl

No

Name of the tumor

Age

Histopathological feature

IHC

Cytogenetics

1.

Small cell ostosarcom a:2,43

Peak in

th

4

decade of life

The cells grow in solid nests or in lobules with densely cellular

central areas and decreasing cellularity with deposition of

more extracellular material

(osteoid) at the periphery

Osteocalcin

Osteonectin

CBFA 1 gene positive.

2.

Round cell liposarcoma

: 2,43

adults, rarely children

Round to angulated small cells

containing one or more lipid droplets, arborizing vasculature, scant myxoid matrix

Vimentin and S-

100 positive.

t(12:16) (q13:p11)

3.

Poorly differentiate d synovial sarcoma:

2,43

Adults

The tumor arises from

pluripotential mesenchymal cells near joints surfaces, tendons -rarely involves head and neck region. Solid small cell areas with round to oval nuclei and scant cytoplasm.

Cytokeratin, EMA

positive.

t(X:18) (p11:q11).

4.

Small cell melanoma:

2,43

Adults

Primitive small cells with scant cytoplasm.

Ultrastructure shows melanosomes.

Positive for S-100, Human Melanoma Black -45 (HMB-

45).

Chromosomes

1, 6, 7, 9, and

10 are preferentially

affected.

5.

Mesenchym al

chondrosarc oma: 43

peak in second decade

Primitive small oval and round cells, hemangiopericytoma vascular pattern, islands of cartilage or hyalinization.

CD 99, S-100 positive and collagen II positive.

Has unique del (13; 21) (q10; q10) translocation.

6.

Small cell

4

carcinoma:

4

Median age 60 years.

Oval to angulated cells with hyperchromatic nuclei and scant cytoplasm, destructive growth pattern, necrosis.

Positive for epithelial

membrane antigen,

cytokeratin, and chromogranin.44

7.

Merkel cell carcinoma:

45

Adults

Tumor originates either from neural crest or stem cell and consists of small blue round cells.

Positive for CK 20 (paranuclear dot),

NSE, NF, EMA, chromogranin, and

synaptophysin.

Table 3: The differential diagnosis summarized in the table form

30 Reshma V, et al. ISSN 2231 - 2250

The Hodgkin’s or RS cells (H-RS cells) are positive for CD30, CD15 (forms paranuclear globule with or without cell membrane staining), HLA-DR, CD25, CD40, CD138 and negative for BCL-6, J-chain and EMA (Epithelial Membrane Antigen). Background cells are usually CD4+ve. Latent membrane protein (LMP) 1 is positive if the patient is
EBV infected.34 Variants of RS cells37 (Fig 5)

1. RS cells of lymphocytic and histiocytic (L and H) type: These RS cells with folded, overlapping nuclear lobes (popcorn) are commonly observed in the lymphocyte predominance type.

2. RS cells of Lacunar type: Characteristic for the nodular sclerosis type of

Hodgkin’s lymphoma, these cells have abundant, lightly acidophilic or water- clear cytoplasm, lobulated nuclei and small nucleoli.

3. RS cells of anaplastic type: Commonly seen in the lymphocyte depletion type, these cells are large and markedly

pleomorphic, with hyperchromatic
bizarre nuclei with prominent nucleoli.

4. RS cells of mummified variant: A degenerated or apoptotic cell that may be seen singly or in clusters. Cells have darkly staining eosinophilic cytoplasm and a dense pyknotic nucleus.


Figure 1: The photomicrograph of hematoxylin and eosin stained section showing Ewing’s sarcoma (a) [Courtesy: Sara Hafezi et al. Ewing’s Family of tumors of the Sinonasal Tract and Maxillary Bone. Head Neck Pathol 2011;5:8-16], poorly differentiated embryonal rhabdomyosarcoma (b) [Courtesy: Enzinger and Weiss. Goldblum JR. Soft Tissue Tumors; 5th edition. China, Mosby, Inc., an affiliate of Elsevier. 2008. 599-618p], True rosettes (c; Arrows) [courtesy:http://www.pathpedia.com/education/eatlas/histopathology/eye_and_ocular_adnexa/reti noblastoma/retinoblastoma], with pseudorosettes [courtesy:http://neuropathology- web.org/chapter7/images7/7-17bl.jpg], diffuse large cell lymphoma (d) [Courtesy: Francisco Vega et al. Extranodal lymphomas of the head and neck. Annals of Diagnostic Pathology: 2005;9:340-

ISSN 2231 – 2250 Small Round Cell Tumor of the... 31

350] and Variants of RS Cells (e): Classical bilobed cell, (f): Popcorn cell, (g): Lacunar variant. [Courtesy: Harry L Ioachim. Lymph node Biopsy. 1st edition, JB Lippincott. 1982.]

Histopathology: WHO classifies Hodgkin’s

lymphomas as:

Nodular Lymphocyte Predominant Hodgkin lymphoma (NLPHL): Multiple crowded or well-separated nodules

consisting of bland-looking small
lymphocytes interspersed with pink- staining histiocytes. L and H cells are found within or in between the nodules. IHC shows L and H cells to be positive for CD 20, BCL-6, J-chain, EMA and CD
40, polytypic B lymphocytes ( Ig M and Ig D +) and CD 3+ T lymphocytes form rosettes around L and H cells.

Classical Hodgkin lymphoma

Nodular sclerosis: Lymph node capsule is thickened with multiple broad birefringent vascularised collagen bands

extending into the parenchyma resulting
in the formation of multiple nodules. The nodules shows presence of lacunar cells arranged singly, in aggregates or in sheets. The background shows small lymphocytes, plasma cells, eosinophils, neutrophils and histiocytes.

Mixed cellularity: The lymphnode is partially or fully effaced and consists of RS cells in the background of eosinophils, neutrophils, lymphocytes, plasma cells and histiocytes.

Lymphocyte rich classical HL: Characterized by diffuse or nodular growth consisting of mononuclear and rare diagnostic RS cells scattered in a

background of small lymphocytes. Do
not show presence of L & H cells.

Lymphocyte depletion: Two types:

o Diffuse fibrosis type: Diagnostic RS cells are rare with background showing disorderly distributed reticular, fibrous and amorphous, proteinaceous material. There is depletion of all cellular elements.

o Reticular Type: Hypercellular with abundance of RS cells but other mature inflammatory cells are sparse. Disordered non-birefringent fibrosis and necrosis are present.34

Immunohistochemistry: The Hodgkin’s or RS cells (H-RS cells) are positive for CD30, CD15 (forms paranuclear globule with or without cell membrane staining), HLA-DR, CD25, CD40, CD138 and negative for BCL-

6, J-chain and EMA. Background cells are usually CD4+ve. Latent membrane protein 1 is positive if the patient is EBV infected. IHC
in NLPHL shows L and H cells to be positive for CD 20, BCL-6, J-chain, EMA and CD 40, polytypic B lymphocytes (IgM and IgD+) and CD 3+ T lymphocytes form rosettes around
L and H cells.35

Cytogenetics: HL is difficult to karyotype, one of the main reason being scarcity of neoplastic RS cells. According to a recent study by Christian Steid et al, copy number alterations found in more than 20% of cases included gains of 2p, 9p, 16p, 17q, 19q, 20q

and losses of 6q, 11q and 13q.44

Conclusion

A precise histological diagnosis of SRCTs was of less relevance when treatment simply
involved resection and radiotherapy, but the continued development of disease-specific
therapeutic strategies, and the concomitant
improvement in prognosis, has rendered accurate tumour diagnosis and classification of paramount importance. Thus, a correct diagnosis is essential for patients with a
small round cell tumour.49 Since these tumors are morphologically similar, a
combination of histopathology, immunohistochemistry and cytogenetics
helps in accurate distinction.

Acknowledgement

We would like to acknowledge Dr. Radhika MB, Prof & Head and Staff members, Department of Oral Pathology, for helping us in preparation of the manuscript.

Author Affiliations

1.Dr.Reshma V, Senior Lecturer, Krishnadevaraya College of Dental Sciences and Hospital, 2.Dr.Kavita Rao, Professor and Head,

3.Dr.Priya NS, Reader, 4.Dr.Umadevi HS, Reader, VS Dental College and Hospital,

5.Dr.Mohsin G, Senior Lecturer, Krishnadevaraya

College of Dental Sciences and Hospital,

6.Dr.Sreelatha Hosthor, Senior Lecturer, Department of Oral Pathology, Rajiv Gandhi

University of Health Sciences, Krishnadevaraya

College of Dental Sciences and Hospital, Bangalore.

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Corresponding Author

Dr. Reshma V

Kluwer business: 2009. P. 313-391.

No 29, MIG, KHB Colony 2nd

stage,

38. Seoane J, Aguirre-Urizar JM, Esparza- Gómez G, Suárez-Cunqueiro M, Campos-Trapero J, Pomareda M. The

Basaveshwarnagar, Bangalore- 560079,

Karnataka State, India. Ph: +91-9916707538

Email: reshmav132@gmail.com

Source of Support: Nil, Conflict of Interest: None Declared.


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