Small round cell Tumors are a group of cytomorphologically similar neoplasm with varied orgin. 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. (Reshma Et al. Small round cell tumor of head and neck region.International journal of oral and maxillofacial pathology.2014)

1. Round Cell Tumors
-Aldrin Jerry.J
Dr.Aldrin Jerry

2. content
• Introduction
• Classification of round cell lesions
• Description of individual round cell tumors
• Conclusion
• References
Dr.Aldrin Jerry

3. Introduction:
• The term ‘small round-cell tumour’ (SRCT) traditionally describes a group of
undifferentiated paediatric tumours that can present diagnostic difficulty because they may
be indistinguishable using light microscopy. [Aidan P. Mcmanus, Barry A. Gusterson. The Molecular Pathology Of
Small Round-cell Tumours-relevance To Diagnosis, Prognosis, And Classification. Journal Of Pathology, Vol. 178: 116--121 (1996)])
• Small round cell Tumors are a group of cytomorphologically similar neoplasm with
varied orgin. 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. (Reshma Et al. Small round cell
tumor of head and neck region.International journal of oral and maxillofacial pathology.2014)
• Heterogeneous group of neoplasms featuring primitive, undifferentiated round-cell
morphology
• Therefore often lacking any particular morphological features that would allow precise
identification.
Dr.Aldrin Jerry

4. • Children (20% of the solid tumors), adolescents and young adults
• Skeletal system or soft tissue
• Immunophenotypic and genetic analysis
• Diagnostic uncertainty
Dr.Aldrin Jerry

5. Working Classification
Dr.Aldrin Jerry

6. Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th editionDr.Aldrin Jerry

7. Classification based on size:
Small round cell lesions:
• Neuroblastoma
• Ewing’s sarcoma/PNET
• Rhabdomyosarcoma (embryonal
type)
• Merkel cell carcinoma
• Mesenchymal chondrosarcoma
• Small cell osteosarcoma
• Squamous cell carcinoma
• Adenocarcinoma
• Melanoma
• Lymphomas
Large round cell lesions:
• Squamous cell carcinoma
• Adenocarcinoma
• Melanoma
• Rhabdomyosarcoma
• Lymphomas
• Paraganglioma
Based On: AIDAN P. Mcmanus*, Barry A. Gusterson. The Molecular Pathology Of Small Round-cell Tumours-relevance To
Diagnosis, Prognosis, And Classification. Journal Of Pathology, Vol. 178: 116--121 (1996)Dr.Aldrin Jerry

8. Classification based on orgins:
Neurogenic origin
• Ewing’s sarcoma and primitive neuroectodermal tumor
• Neuroblastoma
• Merkel cell tumor
• Paraganglioma
• Retinoblastoma
• Medulloblastoma
• Small cell tumor of lung
Mesenchymal origin
• Myogenic differentiation - Rhabdomyosarcoma
• Osteoid differentiation - Small cell osteosarcoma
• Chondroid differentiation - Mesenchymal chondrosarcoma
• Adipose tissue like differentiation - round cell liposarcoma – thigh & popliteal
Malignant soft tissue tumors of uncertain types
• Desmoplastic small round cell tumor – abdominal & pelvic
• Poorly differentiated synovial sarcoma
Hematolymphoid origin - Lymphoma
Based On: AIDAN P. Mcmanus*, Barry A. Gusterson. The Molecular Pathology Of Small Round-cell Tumours-relevance To Diagnosis,
Prognosis, And Classification. Journal Of Pathology, Vol. 178: 116--121 (1996)
Dr.Aldrin Jerry

9. EWING’S SARCOMA
AND
PRIMITIVE NEUROECTODERMAL
TUMOR (PNET)
Dr.Aldrin Jerry

10. EWING’S SARCOMA AND PRIMITIVE
NEUROECTODERMAL TUMOR (PNET)
• distinct clinicopathological entities
• higher degree of neural differentiation in PNETs
• ESFT
• primitive neural crest cells
• spectrum of round-cell sarcomas
Dr.Aldrin Jerry

11. Ewing’s sarcoma: (James Ewing in 1921)
• 6% of all malignant bone tumors
• Site: Primarily affects skeletal system
-4% of Ewing’s sarcoma – head & neck
-1% - jaws – ramus of mandible
• Age: Ewing’s Sarcoma-children & young adults – 5 to 30 yrs
-PNET has broader age range than Ewing’s sarcomas
• Gender : Males > Females
• Symptoms: Painful swelling, aggressive behaviour, rapid growth; Mandible –
loosening of teeth, paraesthesia, otitis media
Dr.Aldrin Jerry

12. Neville. Oral and maxillofacial pathology 1st south asia edition
Dr.Aldrin Jerry

13. Radiographic features:
• non-specific, poorly defined osteolytic lesion and cortical erosion
• Sun-ray spicules of peri-osteal bone
• Onion-skin reaction – laminar periosteal response – rare in jaw bones
Dr.Aldrin Jerry

14. Ewing’s sarcoma:
Monotonous
proliferation of loosely
cohesive round cell
with scant, pale
cytoplasm, round
nucleus, distinct nuclear
membrane, fine
granular chromatin, one
or two nucleoli
Dr.Aldrin Jerry

15. PNET :
Cells with eosinophillic
cytoplasm, vesicular
nuclei and prominent
nucleoli surround a
central fibrillary core
(Homer Wright rosettes).
Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th editionDr.Aldrin Jerry

16. Strong membranous
CD99 immunoreactivity
Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th edition
Dr.Aldrin Jerry

17. Dr.Aldrin Jerry

18. Immunohistochemical findings
• Ewing’s Sarcoma – Neuron specific enolase (NSE), AE1/AE3
• PNET - Neural markers - NSE, S-100, synaptophysin, chromogranin positivity –
at least two neural markers for diagnosis
• CD 99 – 95% cases are positive
Dr.Aldrin Jerry

19. Treatment and prognosis : multimodality treatment.
• Hematogenous spread / lung metastasis
• Prognosis – poor – 60% 5 year survival rates
• Jaw bones – better prognosis than long bones
Dr.Aldrin Jerry

20. MERKEL CELL CARCINOMA
• Cutaneous malignancy of neuroendocrine origin
• 1st described by Toker in 1972
• Age : elderly (>65 yrs)
• Etiology : exposure to solar radiation, immunodeficiency
• Site : head & neck (55%), extremities
• Intra oral- lip is common site, floor of mouth, buccal mucosa, tongue, hard palate
Dr.Aldrin Jerry

21. Clinical features
• Reddish-purple plaque/solitary, painful, rapidly growing nodule
• Advanced lesion- ulcer & hemorrhage and lymphadenopathies
• Occurs in patients with history of multiple skin tumors
• AEIOU
Dr.Aldrin Jerry

22. Pablo Santos Gorjóna,, Ana Cristina Morales Martínb. Merkel Cell Carcinoma: A Presentation of 5 Cases and a Review o the Literature. Acta
Otorrinolaringol Esp. 2011;62(4):306---310
Dr.Aldrin Jerry

23. Histopathology – 3 types
• Trabecular or classic
• Intermediate cellular - most common - existence of a circular
arrangement in nests or rosettes of intermediate cells, accompanied by
a peripheral trabecular pattern
• Small-cell pattern - diffuse infiltrate of neoplastic cells in sheets
• Surface epithelium is intact. Moderately sized, uniform,
undifferentiated basophillic cells in dermis and subcutaneous fat.
Tumor cells have scant cytoplasm, indistinct cell borders, prominent
nuclei.
Dr.Aldrin Jerry

24. • Cells with vesicular nuclei are
observed among the small
round blue cells
Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th edition
Dr.Aldrin Jerry

25. Cells with CK 20
dot like positivity
Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th editionDr.Aldrin Jerry

26. Dr.Aldrin Jerry

27. OLFACTORY NEUROBLASTOMA
• Also known as Esthesioneuroblastoma; Origin : Neuroectodermal cells
• Site: Follows distribution of sympathetic fibers in anterior portion of
nasal cavity
• Age : 5th – 6th decade and 2nd decade
• Symptoms : Nasal obstruction, epistaxis
• Radiographic feature : spotty calcification in tumor
Dr.Aldrin Jerry

28. Dr.Aldrin Jerry

29. Low power view
showing nests of
uniform, small,
round cells in a
fibrovascular
stroma.
Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th editionDr.Aldrin Jerry

30. Poorly differentiated
neuroblastoma.
Small round/ ovoid
cells with
hyperchromatic
nuclei, scant
cytoplasm and
Homer Wright
rosettes
Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th editionDr.Aldrin Jerry

31. Immunohistochemical studies
• Positive for markers for neural or neuroendocrine differentiation
• CK, EMA- in areas with epithelial differentiation-focal
• CD 99 – negative
• Cytogenetic: t (11;22)(q24;q12)
Dr.Aldrin Jerry

32. RHABDOMYOSARCOMA (RMS)
• Commonest soft tissue sarcoma in children (50%)
• 2-5% of adult sarcomas
• Age: bimodal
• Types
-Botyroid RMS (2%)
-Spindle cell RMS
-classical embryonal RMS (71%)
-Alveolar RMS (17%)
-Undiffferentiated RMS
• Gender : Males > Females
• Site : Head and neck- 40%
-Orbit ,nasal cavity, nasopharynx
-Intra oral sites : tongue, lip
• Age : Embryonal: birth – 15 yrs
-Alveolar: 10 – 25 yrs
-Pleomorphic: adults
Dr.Aldrin Jerry

33. Neville. Oral and maxillofacial pathology 1st south asia editionDr.Aldrin Jerry

34. Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th edition
Dr.Aldrin Jerry

35. Botyroid RMS
•Sparsity of cells and
abundance of mucoid stroma
‘Cambium layer’ –
subepithelial condensation
of tumor cells separated
from intact surface
epithelium by a zone of
loose stroma
Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th edition
Dr.Aldrin Jerry

36. Alveolar RMS
• Ill-defined aggregates of poorly differentiated round tumor
cells
• Aggregates of cells are separated by hyalinised fibrous septa
• Cells show loss of cellular cohesion and formation of
irregular ‘alveolar’ spaces
• ‘Solid’ forms without alveolar patterns – similar to embryonal
RMS (regular arrangement of fibrous septa, more uniform
cellular picture)
Dr.Aldrin Jerry

37. Single layer of
neoplastic cells
adheres to dense
fibrous septa with
central loss of
cellular cohesion.
Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th edition
Dr.Aldrin Jerry

38. Fibrovascular
septa lined by a
single layer of
round cells and
loss of cellular
cohesion
Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th editionDr.Aldrin Jerry

39. `
Dr.Aldrin Jerry

40. Embryonal / Alveolar Rhabdomyosarcoma
Special stains
• PAS - abundant intracellular glycogen regardless of type
• Iron Haematoxylin
• Masson Trichrome
Immunohistochemical studies
• Desmin, Myoglobin- well differentiated cells
• Vimentin, CK, S-100- undifferentiated cells
• MyoD1, Myogenin- early stage of skeletal muscle differentiation
Dr.Aldrin Jerry

41. SMALL CELL OSTEOSARCOMA
• Variant of osteosarcoma
• Composed of small cells and varying amount of osteoid.
• Very rare bone tumor - 1% to 1.5% of all osteosarcomas
• Age : All ages; slightly older age group as compared to conventional forms
• Site : majority of tumors - metaphysis of long bones
• Clinical features : local pain/swelling/both
• Radiographic features:
-Mixed lytic and blastic pattern
-Destroys cortex and often extends into the soft tissue
-Mineralized matrix present in most tumors - distinctive feature to
differentiate small cell osteosarcoma from other small, blue cell tumors,
radiographically.
Dr.Aldrin Jerry

42. Uma K, Cherian G, Nayak V, Patil S. Small cell osteosarcoma of the mandible: Case report and review of its diagnostic aspects. J Oral
Maxillofac Pathol 2011;15:330-4.
Dr.Aldrin Jerry

43. Osteosarcoma composed
predominantly of small round cells
adjacent to bands of osteoid
Microscopically
Small cells identical in size to
Ewing/PNET cells and a lace-like
osteoid stroma.
Majority - round tumor cells; rare cases
- short spindle cells
Cytoplasm – scant; Nuclei - round to
oval, fine to coarse chromatin, show
abundant mitoses.
Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th edition
Dr.Aldrin Jerry

44. Immunohistochemistry
• Positive - Vimentin, Osteocalcin, Osteonectin
• Negative - Conventional lymphoid markers
Prognosis: Slightly worse than conventional osteosarcoma.
Management: Surgery with additional chemotherapy
Dr.Aldrin Jerry

45. MESENCHYMAL CHONDROSARCOMA
• 1st described by Lichtenstein and Bernstein, 1959
• 3-9% of all chondrosarcomas
• Malignant cartilaginous tumor- two components
• Tumor of bone & soft tissue- bimorphic histopathological pattern
• Age- 15-35yrs
• Site: head & neck- maxilla and mandible (25-30%)
-1/3rd to 1/4th arise in soft tissues than bone
• Presents as a pain/painless mass
• Radiographically, circumscribed radiolucency, infiltrative margins, stippled
calcifications
Dr.Aldrin Jerry

46. Neville. Oral and maxillofacial pathology 1st south asia editionDr.Aldrin Jerry

47. Neville. Oral and maxillofacial pathology 1st south asia editionDr.Aldrin Jerry

48. Histopathology:
Sheets of patternless masses of small, undifferentiated round cells
Surrounding discrete nodules of well differentiated cartilage
Non-cartilaginous component similar to Ewing’s sarcoma,
hemangipericytoma
Dr.Aldrin Jerry

49. Immunohistochemical studies - non specific
• S-100 positivity- Cartilaginous portion; but negative for areas devoid
of cartilaginous areas
• CD 99 –positive (50%)
• Neuron specific enolase - positive
• Sox9 - a transcription factor – master regulator of chondrogenesis,
primitive mesenchymal cells & cartilagenous tissue - nuclear staining;
negative for all other round cell sarcomas
Dr.Aldrin Jerry

50. Burkitt’s lymphoma
• Age: childhood, rare-adults
• Site: Maxilla, mandible
Clinical features
• African –swelling of infected jaw
• Loosing of teeth
• Lymphadenopathy
Etiology
• t(8;14)(q24;q32)
• HIV,
• EBV
Dr.Aldrin Jerry

51. Histopathology: Low power, numerous pale macrophages producing a “starry sky” appearance.
High power, tumor cells have multiple small nucleoli and high mitotic index. The lack of
significant variation in nuclear shape and size lends a monotonous appearance
Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th edition
Dr.Aldrin Jerry

52. • IHC=CD45, CD 20
Dr.Aldrin Jerry

53. Hogdkin’s lymphoma
Age: Bimodal; young (15-34yrs), Older (>55yrs)
Clinical features: Painless- cervical lymphadenopathy
Site: Usually extranodal, Axilla, Waldeyer ring
Mandible & overlying alveolar mucosa
Etiology - HIV, EBV
Dr.Aldrin Jerry

54. Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th edition
Dr.Aldrin Jerry

55. Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th editionDr.Aldrin Jerry

56. • IHC= CD 15, CD 30
Dr.Aldrin Jerry

57. SQUAMOUS CELL CARCINOMA (POORLY
DIFFERENTIATED)
• Etiology: Tobacco, alcohol, radiation, immunosuppression,
malnutrition etc
• Site :base of tongue, floor of mouth, buccal mucosa, lips, gingiva
• Painless, indurated masses or ulcers with everted margins
• IHC – cytokeratin: +ve; HMB 45 & S100: -ve
Dr.Aldrin Jerry

58. Histology:
-Sheets of cells
-Pleomorphism & hyperchromatism
with many mitotic figures
• -
Squamous cell carcinoma (poorly differentiated)
Dr.Aldrin Jerry

59. MALIGNANT MELANOMA (SMALL CELL VARIANT)
• Variant of Melanoma
• Skin,UV
• Head & neck- sinonasal tract, oral cavity
• Age: above 40yrs
• Brown, bluish polypoid masses
Dr.Aldrin Jerry

60. Neville. Oral and maxillofacial pathology 1st south asia editionDr.Aldrin Jerry

61. Histological:
•small cells, hyperchromasia,
prominent nucleoli, and a large nuclear
to cytoplasmic ratio
•IHC – HMB 45 & S100 +ve;
cytokeratin: -ve
Enzinger and Weiss SW, Goldblum JR. Soft tissue tumors. 5th edition
Dr.Aldrin Jerry

62. LESION ORGIN HISTOPATHOLOGY IHC
EWING’S SARCOMA Neural ectoderm Monotonous proliferation in sheets or
lobular
CD 99,NSE,AE1/AE3
PRIMITIVE
NEUROECTODERMAL TUMOR
Neural ectoderm Homer Wright Rosettes CD 99, NSE, S-100,
synaptophysin,chromogranin
(any 2 makers)
MERKEL CELL CARCINOMA Neuroendocrine Psedoglandular, Trabecular, Cribriform
(swiss cheese) and Sheets
CK 20, EMA and AE1-AE3,
NSE, chromogranin,
synaptophysin
OLFACTORY NEUROBLASTOMA Neuro ectodermal Sheets, Lobular, Homer Wright Rosette,
Psedorosette
Dr.Aldrin Jerry

63. Conclusion
Round-cell lesion certainly represent the model of how the
integration of different diagnostic tools (morphology,
immunohistochemistry, molecular genetics) may impact on the accurate
diagnosis and classification of tumours.
Dr.Aldrin Jerry