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228 Indian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3
Round Cell Tumors - Classification & Overview
Kush Pathak1, Prachi Nayak2, Asha Karadwal3, Sushruth Nayak4, Satyajit Tekade5
1AssociateProfessor, 2Professor, 3Reader, 4Professor & Head, Department of Oral Pathology & Microbiology,
M. M. College of Dental Science & Research, M.M(Deemed to be) University, Mullana (Ambala), 5Professor &
Head, Department of Oral Pathology & Microbiology, Modern Dental College & Research Centre, Indore (M.P)
Abstract
Round cell tumors from time indefinite have been affecting mankind, not only by their dangerous and life
threatening nature but also by their vast variety. Number of tumors share similar histology, composed of
relatively uniform primitive Small Round Blue Cells. They also share many demographic, radiographic
and clinical similarities, which often lead to misinterpretation and wrong diagnosis. These tumors, although
sharing similar looks which is quite confusing, come from different origin, in different sizes, colors, site of
action & most importantly nature. A few are aggressive and others are latent and benign. In some cases the
etiology is known, however on the other hand a large number of these tumors have an idiopathic etiology.
Whatever the lesion or however the appearance clinically, histopatholgically or cytologically, these round cell
tumors, continue to fascinate and confuse us & lack of a proper classification adds to the misinterpretation.
This review article is thus an attempt to go through this vast variety of tumor thoroughly along with an
attempt to provide a proper classification for the tumor itself.
Keywords - Small round blue cell tumors, Ewings/PNET, Rhabdomyosarcoma, Wilm’s tumor, Lymphoma,
NUT (Nuclear protein in testis) carcinoma
Introduction Classification:
The term small round cells associates to lesions I) According to ROUND CELL PATTERN
having dominant small cell population with basophilic
nuclei and little or complete absence of cytoplasm. A. Diffuse round cell pattern
The large round cell tumors are those which consists 1. Ewing`s sarcoma
relatively larger cells than typical small round cell
tumors. Such round cell tumors present a distinct 2. Primitive neuroectodermal tumor
histological pattern along with immunohistochemical
3. Merkel cell carcinoma
and electron microscopic characters, thus helping with
differential diagnosis.1 4. Embryonal rhabdmyosarcoma
Thus an attempt was made at classifying these 5. Small cell neuroendochrine carcinoma
tumors based on various factors : -
6. Lymphoma
7. Leukemic infiltrate
Corresponding Author:
Dr. Kush Pathak, MDS, B. Septate or lobulated round cell pattern
Associate Professor, Department of Oral Pathology
& Microbiology, M.M.College of Dental Science & Small round cells are divided by fibrous/
Research, M.M(Deemed to be) University, fibrovascular septate
Mullana (Ambala)
Email: dr.kushpathak2011@gmail.com 1. Ewing`s sarcomaIndian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3 229
2. Alveolar Rhabdomysarcoma (ARMS) (NUT), Small cell carcinoma, PNET, Ewing’s
sarcoma, melanoma, ARMS, langerhans cell disease,
C. Alveolar/ Pseudoalveolar round cell pattern
Non Hodgkin’s lymphoma, adenocarcinoma,
Focally placed, with poorly cohesive round cell neuroendocrine carcinoma, merkel cell carcinoma,
population in pseudo alveolar appearance. NBL, nephroblastoma/wilm’s tumor, hepatoblastoma,
retinoblastoma, desmoplastic small round cell tumor.2
1. ARMS
B. Large round cell -Melanoma, Undifferentiated
2. Primitive neuroectodermal tumor (PNET) carcinomas, mesothelioma, large round cell sarcomas
(epitheloid sarcoma, malignant peripheral nerve sheath
D. Round cell pattern with Rosettes
tumor, atypical cellular neurothekeoma), large round
`Rosette’ pattern means flower like arrangement. cell lymphomas (large cell diffuse B-cell lymphoma,
In this pattern a central area is surrounded by radially classical Hodgkin’s lymphoma).3
arranged cells from all the sides.
III) According to the origin -
1. True - Flexner’s(Flexner- Winterstein, true
v Neurogenic origin:
rosettes)-They are composed of tumor cellssurrounding
a lumen of cytoplasmic extensions. Eg. Retinoblastoma 1. Ewing’s sarcoma/ PNET
2. Pseudorosettes - 2. Neuroblastoma
a. Homer Wright rosette- The center has abundant 3. Retinoblastoma
fibrillarmaterial
4. Medulloblastoma
eg .Olfactory neuroblastoma, medulloblastoma,
pinealoblastoma, PNET 5. Merkel Cell Tumor
b. Perivascular pseudorosette 6. Paragangliomas
c. Pineocytomatous/neurocytic pseudorosettes 7. Small Cell Tumor of Lung
d. Ependymal rosettes (ependymoma) v Mesenchymal origin:
E. Round cell pattern with 1. Myogenic differentiation - Embryonal
hemangiopericytomatous vascular pattern Rhabdomyosarcoma, Alveolar Rhabdomyosarcoma
1. Poorly differentiated synovial sarcoma 2. Osteoid differentiation:Small Cell
Osteosarcoma
2. Mesenchymal chondrosarcoma
3. Chondroid differentiation:Mesenchymal
F. Round cell pattern with other components chondrosarcoma
1. Pseudo glands- Poorly differentiated synovial 4. Adipose tissue like differentiation:Myxoid/
sarcoma Round Cell Liposarcoma
2. Cartilage- Mesenchymal chondrosarcoma 5. Malignant Soft Tissue Tumors of Uncertain
Type:Desmoplastic Small Round Cell Tumor, Poorly
3. PNET/Extraskeletal Ewing’s sarcoma(ES)
Differentiated Synovial Sarcoma
II) According to size of round cell –
v Hematolymphoid Origin:
A. Small round cell - Squamous cell carcinoma
ü Lymphoma/ ‘Reticulum Cell Sarcoma’230 Indian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3
According to a study conducted in 2016, Non- and within soft tissues.5
Hodgkins Lymphoma, Neuroblastoma, Ewing/PNET
ES is a primary malignant tumor of bone, composed
and Rhabdomyosarcoma were the most frequent Round
primarily of small undifferentiated round cells of
cell tumors. It was also confirmed that Neuroblastoma,
uncertain histogenesis and can also occur within soft
Retinoblastoma, Wilms Tumor, Hepatoblastoma
tissue (extraosseous ES) whereas PNET is a soft tissue
have presentations in early childhood while
tumor.6,7 Data obtained from recent studies show that in
Rhabdomyosarcoma are seen throughout childhood.4
most cases of ES, features aresimilarto neuroectodermal
Following the above study only the most common origin.8
round cell tumors along with a few important ones are
PNETs, despite their name, are slightly less primitive
discussed in detail below.
than ES and show features of neural differentiation.
EWING’S SARCOMA & PNET PNET is a small round cell malignancy of primitive,
neuroectodermal tissue or pluripotential, migratory
ES & PNET, are opposite ends of spectrum of
neural crest cells that arises from the soft tissue or bone,
primitive neural tumors. They share a variety of clinical,
commonly affecting older children and adults.8
morphological, cytologic differentiation and are one of
the commonest tumors of childhood and occur in bone
Table 1: Features include9 :-
Ewing’s sarcoma9 PNET9
Histopathology -
Histopathology -
1. Irregular cells
1. Uniform round cells
2. Coarse chromatin
2. Fine chromatin
3. Prominent nucleoli
3. Pin point nucleoli
4. Scanty glycogen
4. Abundant glycogen
5. HW rosettes & Sometimes FW rosettes
5. Rosettes absent
IHC
IHC
1. Shows positivity to Neural markers- Neuron specific
1. Shows positivity to NSE, AE1/AE3 (epitheloid pattern)
enolase, S-100, synaptophysin, chromogranin. The positivity
to atleast two neural markers is required to give a diagnosis
2. Positive to CD99 (90%), Vimentin, Neuron specific enolase
of PNET.
Special Stains:
2. Positivity to CD99 (90%), Vimentin, Neuron specific
Abundant intracellular glycogen - PAS positive (More
enolase.
intense than PNET)
Special Stains:
Abundant intracellular glycogen - PAS positive
Merkel Cell Carcinoma & epidermis. They have close association to peripheral
nerve ending & function as sensory touch receptors. They
It is a malignancy of cutaneous region and
consists of neuroendocrine granules in the cytoplasm.10
neuroendocrine origin. Local recurrence and distant
metastasis is commonly seen. It is caused due to UV radiation, long term
immunosuppression and Merkel cell polyomavirus
Merkel cells which are the cells of origin, are clear
(MCPyV). MCPyV is the only polyomavirus associated
cells seen in basal & suprabasal layer of oral mocosa
with human cancer. Typically, healthy individuals areIndian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3 231
not affected, however catastrophic diseases can occur in Rhabdomyosarcoma was proposed. 17,18
immunocompromised hosts. This mainly happens due to
International Classification system for childhood
MCPyV genome getting integrated within the precursors
Rhabdomyosarcoma18
of MCC. Virus-positive MCC often occur with specific
mutations in tumor suppressing genes and tumor A) Superior Prognosis
oncogenes.This combination of an innocuous virus with
exceedingly rare integration pattern may account for i. Botryoid
rarity of MCC. Although the exact percentage of MCC
ii. Spindle cell
tumors containing MCPyV is not known, there is an
estimate of about 80% cases by several reports.11 B) Intermediate Prognosis
Studies have shown that MCPyV does not play a i. Embryonal
major role, but immunosuppression as well as the use of
C) Poor Prognosis
tobacco and alcohol increases the risk.12
i. Alveolar
Head & neck and extremities are common sites of
occurrence. Intraorally lip is common site followed by ii. Undifferentiated Sarcomas
floor of mouth, buccal mucosa, tongue& hard palate.
Clinically it appears as plaque like advanced lesion with D) Subtypes whose prognosis is not presently
ulcer, haemorrhage and rapid growth. evaluable
Histologically MCC are divided into three types: i. RMS with Rhabdoid features
Trabecular, intermediate and small cell.13Cells in the
The latest WHO classification for myogenic tumors,
trabecular type are arranged compactly in a trabeculae,
published in 2013, created the SCRMS and SRMS as a
showing abundant cytoplasm with few mitoses. It
new specialized subgroup based primarily on experience
has the best prognosis and is infrequent. On the other
with adult tumors.19
hand solid and diffuse growth pattern, less abundant
cytoplasm, frequent mitoses and focal necrosis is noted Benign -
in intermediate type. It is the most frequent and clinically
Rhabdomyoma, adult type
aggressive subtype. Whereas, small cell type presents
itself in clusters and solid sheets of cells. Clinically it is Rhabdomyoma, fetal type
equally aggressive to intermediate type.10
Rhabdomyoma, genital type
RHABDOMYOSARCOMA [RMS]
Malignant -
It is a malignant neoplasm of skeletal muscle origin
but can also arise in tissues where striated muscles are Embryonal Rhabdomyosarcoma
not normally found like urinary bladder. It is the most
Alveolar Rhabdomyosarcoma
common soft tissue sarcoma in children, accounting
for 4.5% of childhood cancers14and is the third most Pleomorphic Rhabdomyosarcoma
common neoplasm after neuroblastoma and wilm’s
Spindle cell/Sclerosing
tumor among extra cranial solid tumors of children. It
Rhabdomyosarcoma
can occur anywhere but most common site is head &
neck followed by genitourinary tract. Males are more Embryonal rhabdomysarcoma [ERMS]
commonly affected than females with a ratio of 1.3-1.4:
1.15,16 As there was no overall agreement on the standard Approximately 60% of all newly diagnosed RMS
classification given by Horn & Enterline in 1958, an are of embryonal type, and usually happen in younger
international classification system for childhood RMS, children20.The incidence is highest in children between232 Indian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3
1-4 years. The most commonsiteis orbit. In oral cavity, in the extremities of adult males and is very aggressive.
tongue followed by soft palate, hard palate and buccal Age range was between 28.4 - 92.8 years with 71.5 years
mucosa are commonly affected. 21 to be median age. The median survival ratein patients
with localized (n=32, 71.1%) and metastatic disease
Alveolar rhabdomyosarcoma [ARMS]
(n=13, 28.9%) was 12.8 months. 26
It constitutes roughly around 20 to 30% of all RMS
Histopathologically, PRMS is composed of large,
tumors, mainly affecting olders and has worse prognosis
heterogeneous, polygonal pleomorphic rhabdomyoblasts
than other types.It commonly affects head and neck,
with abundant eosinophilic cytoplasm. These large
urogenital tracts, torso and extremities of both males and
rhabdomyoblasts are often found as clusters, plates,
females. ARMS is an aggressive subtype with a higher
or scattered individual cells. Predominating cells are
rate of metastasis. It is derived from the precursor cells
atypical showing vesicular nuclei with prominent
present within the muscles. Multiple events of genetic
nucleoli. Shape of the rhabdomyoblasts vary from round
recombination act together developing the fusion
to spindled. Three morphological variants of PRMS
protein, which then finally leads to dysregulation of
have been proposed and should be positive with atleast
transcription, thus acting as an oncogene. 22
one specific skeletal muscle marker in addition to other
PAX3-FOXO1 (Positive in~60% cases),PAX7- muscle markers.27
FOXO1(positive in 20%) are the two main fusion
Type I or “classic PRMS”
proteins that can be associated with ARMS and 20%are
fusion negative ARMS cases.23 Type II, also termed “round cell PRMS”
Histopathology (ERMS vs ARMS) - ERMS looks Type III, or spindle cell PRMS
similar to embryonic muscle & comprises of round or
Botryoid Rhabdomyosarcoma - It is a subtype of
spindle shaped cells, whereas ARMS presents a distinct
embryonal RMS. An aggressive malignancy arising from
alveolar architecture. Small round undifferentiated cell
embryonal rhabdomyoblasts.17 It can arise anywhere in
aggregates are separated by dense hyalinized fibrous
the body from muscle tissue, but specifically in Botryoid
septa. Despite of high muscle differentiation marker in
form. It tends to hollow organs with a mucosal lining
ARMS, there is lack of mature muscle characteristics.
such as the bladder, uterus and vagina. Female infants
This alveolar structure is absent in some solid ARMS
and young children are commonly affected.It is mainly
variants and histological features overlapping ERMS
asymptomatic with urination & vaginal symptoms. Gross
might be seen. Recently introduced cytogenic &
characteristic appearance are only present in sarcoma
molecular screening has improved the diagnosis.24
botryoides and they present themselves as a polypoidal
According to a study conducted in 2017, PTAH mass. Mainly affecting the genital and urinary tract, this
stain was not having any added value to confirm the is a macroscopic morphological feature of the embryonal
diagnosis of RMS, thus makingthe use of IHC a useful type.28
and important step as confirmation test for all cases
NEUROBLASTOMA [NBL]
suspected to be RMS.25
Neuroblastomas are rare and affect 1 in 8000 live
Thus only IHC was discussed further on in the
births & represent 6-10% of all childhood tumors.29They
article. However, other special stains that could be
are commonest extracranial solid tumors of childhood
used in this case are Iron haematoxylin, Masson
with neoplastic expansion of neural crest cells in
Trichrome(Rhabdomyoblasts).
developing sympathetic nervous system. They most
Pleomorphic Rhabdomyosarcoma [PRMS] frequently arise from adrenal gland. Prognosis varies
-Mainly affects older patients. A 19 year long extensive widely from regressing on its own to wide metastases
study revealed that clinically, PRMSpredominantly arises and resistance to treatment leading to mortality. It canIndian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3 233
be sporadic or nonfamilial in origin30 and constitutes 5% with “unfavorable” histology demonstrate higher
of malignancies of sinonasal tract. Adults are commonly degrees of anaplasia with association to poor prognosis
affected with age ranging between 5th - 6th decade and and survival.34
a smaller peak in 2nd decade of life. Nasal obstruction,
MESENCHYMAL CHONDROSARCOMA
epistaxis, anosmia are most common symptoms.
[MC]
Histopathological examination reveals NBL
It accounts for 2–10% of all chondrosarcomas.
comprised primarily of immature neuroblasts, which are
This histological subtype occurs in both osseous and
small, undifferentiated and round shaped sympathetic
extraosseous tissues.36Extraaxial MC is an aggressive
cells with little cytoplasm, dark nuclei & small
neoplasm with poor prognosis.37
indistinct nucleoli. Seldom, clusters of cells, termed as
Homer-Wright rosettes are formed which are typical Bishop et al in their 24 year long study concluded
characteristic of NBL.31 it is a rare malignant cartilaginous tumor composed of
two components, sheets of primitive mesenchymal cells
Wilm’s tumor
& interspersed islands of well differentiated hyaline
Nephroblastoma or Wilms’ tumor is an embryonic cartilage38. Females are more affected than males with
tumor derived from primitive renal epithelial and median age of 14.5 years and a range of 1.2 - 19.7 years.
mesenchymalcomponents.32 It is common among Orbit is most commonly affected in head & neck region.
children with renal cancer and accounts for 6% of all Other sites are maxillary sinus, soft tissue of face &
malignancies.33 Although the causes are unknown, it neck, chest wall, intra abdominal and lumbar para spinal
is believed that they occur due to genetic alterations areas. Metastases was also noted to lung parenchyma.
dealing with normal embryological development of the Pain, swelling, proptosis were common symptoms.
genitourinary tract. It is also most common abdominal Radiographs showed soft tissue mass with calcified
cancer and fourth most common pediatric cancer areas, followed by bony destruction of primary structures
overall. Typically presenting between 3 to 5 years, or with variable patterns of postcontrast enhancement.38
90% occurring in less than six years of age34. There is a Histological examination characterizes MC by a biphasic
slight female predilection. 35 pattern, composed mainly of undifferentiated small
round cells blended with islands of well-differentiated
Wilm’s tumor is also associated with syndromes like
hyaline cartilage. Hemangiopericytoma-like pattern is a
WAGR syndrome (50% chance of developing Wilm’s
common finding.39,40
tumor), Denys-Drash syndrome/ Drash syndrome(90%
chances), Beckwith-Wiedemann syndrome (5-10% SYNOVIAL SARCOMA (POORLY
chances).34 Association with several other syndromes DIFFERENTIATED)
can be found, but the ones stated here are most common.
Synovial sarcoma is a rare soft tissue tumor
Common symptoms include abdominal pain, commonly involving the extremities of young adults.
hematuria, urinary tract infections, hypertension or
Poorly differentiated formhas a poor prognosis
hypotension, fever, anemia. Sometimes lung metastases
which is negatively affected by histology, advanced
presenting with dyspnea or tachypnea may be seen.34
age and increased size. Theymake up for only 20%-
Histopathologically it can be divided into 36% of synovial sarcomas. They are rarely seen in older
“favourable” (90% cases) and “unfavourable” histologies. individuals with only 10% seen above 60.Although it is
“Favorable” histology commonly has a better prognosis. very uncommon in the joint cavities and in areas of clear
It shows a triphasic pattern of blastema, epithelial, and association without synovial structures, it is a clinically
stromal tissues. Blastema is most malignant component and morphologically well-defined entity. It occurs
comprising of bundles of small, round blue cells with primarily in close association with tendon sheaths &
high mitotic activity and overlapping nuclei.Tumors joint capsules.Hypopharynx, postpharyngeal region and234 Indian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3
parapharyngeal space in head & neck region followed with cranial nerve involvement. Radiographic features
by mandible are commonly affected sites. Male are more showed aggressive opaque mass involving the skull base
commonly affected.41 Histopathologically sheets of which may extend into the orbits or brain. Rapid growth,
neoplastic cells with nuclear pleomorphism, increased poor prognosis, regional recurrence & distant metastases
mitotic rate along with interspersed atypical forms, zones were noted 49.
of necrosis, and negative margins were observed.41
Histopathologically, nests, trabeculae, ribbons
SMALL CELL NEUROENDOCRINE & sheets of medium sized polygonal cells often with
CARCINOMA an organoid appearance are seen. Pleomorphic &
hyperchromatic round to oval nuclei are seen. The
It is a high grade neuroendocrine neoplasm
chromatin varies from diffuse to coarsely granular &
resembling anaplasticsmall cell carcinoma of other
the nucleoli is typically large. Individual cell necrosis
organs/lung. They arise from multipotent stem cells42.
& central necrosis of cell nests,with increased mitotic
Patients between 3rd-5th decade are affected43. They are
activity is present. Occasional severe dysplasia or
most frequently found in lungs with about 4% cases in
carcinoma insitu of surface epithelium is seen. Invasion
extrapulmonary sites. Parotid, minor salivary glands,
of lymphovascular and perineural areas are common.50
larynx, sinonasal region, hard palate, maxillary sinus are
the areas getting affected. Symptoms include hematuria, LYMPHOMAS
back pain or abdominal pain44. It is very aggressive
According to studies performed in 2013 & 2019, it
withmedian survival between 8 - 20 months45.
was found that non-hodgkins lymphoma is one of the
Radiographic features show medullary location and
most common round cell tumors, comprising of about
lack of central necrosis in a large tumor46. Often local
15% cases.51,52
or distant metastases is seen.Histopathology revealed
fibrocollagenous tissue invaded by small round cells 5% of Head and neck malignanciesare NHL /
having hyperchromatic nuclei and scanty cytoplasm. extranodal natural killer / (NK) T-cell lymphomas and
Focally, rosettoid arrangement of cells were noted.47 have a variety of manifestations. This occurs because
of immunosuppressioncaused by T-cell function, loss
SINONASAL UNDIFFERENTIATED
of control of latent EBV infection and chronic antigen
CARCINOMA [SNUC]
stimulation.53
It is a rare, poorly differentiated and
Histological pattern seen in non-hodgkin’s
aggressivemalignancy of the nasal cavity and paranasal
lymphoma can either be nodular or diffuse. In the
sinuses.48 It appears to be undifferentiated neoplasm
nodular pattern, neoplastic cells collect in large clusters.
with varying degrees of neuroendocrine differentiation.
The diffuse pattern is characterized by a monotonous
It’s pathogenesis includes EBV & loss of retinoblastoma
distribution of cells, without nodularity or germinal
tumor suppressor gene function. Both young and older
center formation and complete destruction of the lymph
patients are affected. A case report showed 60 year old
node structure.6
smoker with one or more symptoms like facial pain, nasal
obstruction, proptosis, epistaxis, periorbital swellingIndian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3 235
TABLE 2: OTHER ROUND CELL TUMORS INCLUDE:
Small cellosteosarcoma 54
Malignant tumor whose cells produce
NUT carcinoma (Squamous cell
bone.
carcinoma)54
Mucosal melanoma54 M=F
NUTM1 gene rearrangement-
Variable Morphologies present within Generally spontaneous, but post
shows abrupt evidence of squamous
a single tumor. radiation and pagets d/s act as etiologic
differentiation.
agents.
Abrupt keratinization present.
Histopathology -
l Neoplastic cells are anaplastic
Histopathology -
Histopathology - and pleomorphic polygonal to
l Undifferentiated small round blue
Cells range from undifferentiated to epitheloid cells set within the
cells.
epitheloid, spindled, plasmacytoid and bony matrix.
l Areas of necrosis.
rhabdoid in same tumor. l Bone remodeling and destruction
l Areas of abrupt squamous
at periphery of tumor.
differentiation.
l Immature lace like osteoid to
more sclerotic & mineralized
bone.
TABLE 3: Immunohistochemistry
Merkel Cell Carcinoma12 Positive -CK20, Chromogranin A, Synaptophysin, NSE, CD56
Positive -Desmin (solid variant of ARMS), Myoglobin (Specific), Myogenin
Rhabdomyosarcoma55
(Sensitive & Specific), MyoD1, Vimentin
Positive- Ki67 (High in embryonal cells), Synaptophysin/GFAP (neural
Neuroblastoma56
markers), Neurofilament protein, NB84
Positive -(Most sensitive-90% cases, CD56,CD57, CK22,CK18, CK8, EMA,
Wilm’s tumor/Nephroblastoma57,58,59
SMA, Actin, Dermin, PAX8, Cyclin D1, Vimentin, BCL2, CD34.
Positive -Vimentin & CD99(+ undifferentiated cells), S100 (+ cartilaginous
Mesenchymal Chondrosarcoma60,61,62
component), Sox9 (nuclear positivity)
Positive - CD99 (91% cases), CD56 (100%), Calretinin (56-71%), TLE1 (80-
Synovial Carcinoma (Poorly
90% cases, specific & sensitive), CK (90%), EMA, BCL2, NY-ESO-1, SYT
differentiated)63
(87% - strong nuclear staining)
Positive - NSE (62%), CD56 (76%), Synaptophysin (95%), Chromogranin A
Small cell Neuroendocrine carcinoma64
(62%), p53, BCL2, S100
Positive - Pancytokeratin (AE1/AE3), CK7, CK8, CK19, p63, epithelial
Sinonasal undifferentiated carcinoma65
membrane antigen, NSE
CD45RB, cytoplasmic CD3, cytotoxic markers, CD56.
Non Hodgkin’s lymphoma54
Multiple Myeloma66 CD138, CD38, MUM1, EMA, CD56, Cyclin D1236 Indian Journal of Forensic Medicine & Toxicology, July-September 2021, Vol. 15, No. 3
Conclusion neuroectodermal tumor of the orbit. Indian J
Ophthalmol. 2009;57(5):391–3
Being one of the most confusing and least explained,
9. Rekhav K, D P, L A, B S AK, M P, Prasanna K.
round cell tumors will continue to fascinate us for a
Histological diversity and clinical characteristics
long time. This review article was a mere step towards
of Ewing sarcoma family of tumors in children:
explaining and clearing out the thin line between these A series from a tertiary care center in South India.
tumors. Use of immunohistochemistry, FNAC, reverse Indian J Cancer. 2015;52(3):331
transcriptase PCR is crucial for early differentiation and 10. Hendrikx SMGA, de Wilde PCM, Kaanders
diagnosis of this group of tumors, which can further JHAM, Blokx WAM, Poorter RL, Merkx MAW.
help in accurate treatment procedures. However, further Merkel cell carcinoma in the oral cavity: A case
studies and reviews are needed to completely understand presentation and review of the literature. Oral
the mechanism of action and etiology of these tumors. Oncol Extra. 2005;41(9):202–6.
Only then can we eradicate the misdiagnosis which often 11. DeCaprio JA. Merkel cell polyomavirus and
comes in handy with these round cell tumors. Merkel cell carcinoma. Philos Trans R Soc Lond B
Biol Sci. 2017;372(1732):20160276.
Conflict of Interest - None
12. Islam MN, Chehal H, Smith MH, Islam S,
Ethical Clearance - Since it was a review article, Bhattacharyya I. Merkel cell carcinoma of the
buccal mucosa and lower lip. Head Neck Pathol.
no ethical clearance was needed.
2018;12(2):279–85.
Source of Funding - Self 13. Gould VE, Moll R, Moll I. Neuroendocrine
(Merkel)cells of the skin: hyperplasias, dysplasias,
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