round cell tumors final
TRANSCRIPT
![Page 1: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/1.jpg)
ROUND CELL TUMORS
Presented by:
Dr. Kush Pathak
![Page 2: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/2.jpg)
Contents Introduction Classification Description of individual round cell tumorsEwing’s SarcomaPrimitive neuroectodermal tumorMerkel cell carcinomaRhabdomyosarcomaSmall cell carcinomaLymphomaSmall cell osteocarcinomaMesenchymal Chondrosarcoma
![Page 3: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/3.jpg)
Round cell liposarcomaDesmoplastic small round cell tumorSynovial Carcinoma
![Page 4: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/4.jpg)
Introduction
The term small round cells are used to describe the
lesions in which dominant population consists of
relatively small cells with basophilic nuclei and little or
no cytoplasm.
The large round cells tumors are those which consist
relatively larger cells than typical small round cell
tumors.
These round cells tumors have several histological
pattern, immunohistochemical & electronmicroscopic
features that can help in differential diagnosis.
![Page 5: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/5.jpg)
Classification ROUND CELL PATTERN
Diffuse round cell pattern
Ewing`s sarcoma
Primitive neuroectodermal tumor
Merkel cell carcinoma
Embryonal rhabdmyosarcoma
Small cell carcinoma
Lymphoma
Leukemic infiltrate
![Page 6: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/6.jpg)
Septate or lobulated round cell pattern
Small round cells are divided by fibrous/fibrovascular
septate
Ewing`s sarcoma
Alveolar Rhabdomysarcoma
Alveolar/ Pseudoalveolar round cell pattern
Focal, poor cohesion of the round cell population resulting
in pseudo alveolar appearance
Alveolar Rhabdomyosarcoma
Primitive neuroectodermal tumor
![Page 7: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/7.jpg)
Round cell pattern with Rosettes
A `rosette’ is like a flower, with the cells being arranged
radially around a central area.
Flexner’s( also called Flexner- Winterstein, true rosettes)-
contain clearly delineated empty central lumen.
e.g. Neuroblastoma
Primitive neuroectodermal tumor( PNET)
Homer Wright rosette-center has no lumen,but abundant
fibrillary material
e.g. Neuroblastoma
![Page 8: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/8.jpg)
Round cell pattern with hemangiopericytomatous vascular pattern
Poorly differentiated synovial sarcoma
Mesenchymal chondrosarcoma
Round cell pattern with other components
Pseudo glands- Poorly differentiated synovial sarcoma
Cartilage- Mesenchymal chondrosarcoma
Primitive Neuroectodermal tumor( PNET)/ Extraskeletal
Ewing’s sarcoma
( ES)
![Page 9: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/9.jpg)
II) According to size of round cell:
Small round cell – Squamous cell carcinoma, PNET,
Ewing’s sarcoma, melanoma, rhabdomyosarcoma,
langerhans cell disease, lymphoma, adenocarcinoma,
neuroendocrine carcinoma, merkel cell carcinoma,
olfactory neuroblastoma
Large round cell - Squamous cell carcinoma,
adenocarcinoma, melanoma, rhabdomyosarcoma,
lymphoid tumors, paraganglioma.
![Page 10: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/10.jpg)
Neurogenic origin:
• Ewing’s sarcoma/ PNET
• Neuroblastoma
• Retinoblastoma
• Medulloblastoma
• Merkel Cell Tumor
• Paragangliomas
• Small Cell Tumor of Lung
![Page 11: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/11.jpg)
Mesenchymal origin:
• Myogenic differentiation
Embryonal Rhabdomyosarcoma
Alveolar Rhabdomyosarcoma
• Osteoid differentiation:
Small Cell Osteosarcoma
• Chondroid differentiation:
Mesenchymal chondrosarcoma
• Adipose tissue like differentiation:
Myxoid/ Round Cell Liposarcoma
![Page 12: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/12.jpg)
Hematolymphoid Origin
Lymphoma/ ‘Reticulum Cell Sarcoma’
Malignant soft tissue tumors of uncertain
type
Desmoplastic small Round cell tumor
Poorly differentiated synovial sarcoma
![Page 13: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/13.jpg)
Small Blue Round cell tumor
Desmoplastic small round cell tumor
Ewing’s Sarcoma/ PNET
Neuroblastoma
Medulloblastoma
Rhabdomyosarcoma
Wilm’s Tumor
Retinoblastoma
Small cell lymphomas
Hepatoblastoma – only the anaplastic form has round blue
cells, the more common fetal and embryonal types do not
![Page 14: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/14.jpg)
Primitive (undifferentiated) nerve cells
Retinoblastoma:
o Flexner- Wintersteiner rosettes: 1891 and 1897
o Knudson’s two hit hypothesis 1970
Medulloblastoma:
o 1973 WHO – posterior fossa PNET
Merkel cells - touch receptors 1875
Ewing’s sarcoma
o John Ewing – 1920
o Established a ‘new’ bone tumor; not a lymphoma
![Page 15: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/15.jpg)
Age/ Gender Site
Retinoblastoma Bilateral – 13 months; unilateral-24 months; M=F
Eye…….. Long bones
Neuroblastoma 2 to 5 yrs; congenital; M:F=1.22:1
Distribution of symp ganglia: base of skull, pelvis, adr medulla
Medulloblastoma Childhood; common 3 to 8 yrs; M > F
Cerebellum
Ewing’s/ PNET Adolescents/ young adults;
M>F
Long bones, extraskeletal – upper thigh and arm, shoulder/ paravertebral, chest wall
Paraganglioma 4th to 5th decades Abdomen (85%), thorax –(12%), H&N (3%) - Carotid body, vagus, larynx
Small Cell carcinoma of Lung
4th decade and above Hemithorax, mediastinum, lymph node metastases
Merkel Cell Carcinoma 7th to 8th decade; M:F=1:4 Skin - periorbital
![Page 16: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/16.jpg)
Clinical Features
Retinoblastoma Familial or de novo. White reflexes, strabismus; 2nd primary neoplasms in adolescence
Neuroblastoma 25% Congenital, non-specific symp, nodular swelling; cutaneous blue-red metastases, MIBG labeling; osteolytic bone lesions – skull, femur, humerusIncreased serum catecholamines, ferritin
Medulloblastoma Headaches, vomiting, visual impairment, nystagmus, muscular in coordination/ weakness, slurred speech
Ewing’s/ PNET Rapidly growing mass, 33% painful, sensory/ motor disturbance if nerves involved
Paraganglioma Multifocal , 10% familial – autosomal dominant, von Hippel Lindau disease; Painless, slowly growing, mobile , bruit (CBP); arteriography – enlarged, tortuous, vessels, displacement of bifurcation; Carney’s complex, MEN types I and II
Small Cell Carcinoma Lung
Smokers; cough, haemoptysis, dyspnoea, chest pain, loss of weight
Merkel Cell Carcinoma
Red/pink/blue nodular tumors; sun exposed surfaces; rapid invasion
![Page 17: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/17.jpg)
Histopathology Prognosis
Retinoblastoma Round cells in true (FW) and pseudo (Homer-Wright) rosettes
90% if optic nerve uninvolved; 20 to 40% if involved; surgery and chemotherapy
Medulloblastoma Round, primitive cells, scant cytoplasm, hyperchromatic nuclei; HW rosettes
30% to 70% 5 yr survival;
Surgery, radiation, chemotherapy
Neuroblastoma sheets- round cells; lobules; no cytoplasm, deep blue cytoplasm; calcifications; HW rosette
Variable: spontaneous remission to poor prognosis;
Surgery - usually
Ewing’s/ PNET Uniform round/ ovoid nuclei; sheets or rosettes; scant cytoplasm, i/c glycogen
65-70% with chemotherapy.
Metastatic disease is 25-30%.
Paraganglioma Nests of cells – round nuclei, abundant cytoplasm, arranged in nests around vascular space (zellballen)
Good for resectable lesions; fatal if not resected 28% 5yr survival; surgery
Small cell carcinoma Lung
Small cells (< lymphocytes), scant cytoplasm, granular chromatin; sheets; EM: neurosecretory granules
5 yr survival 5% to 10%;
Radiation, chemotherapy
Merkel Cell Carcinoma
Large, closely packed round cells, min cytoplasm; nests pattern
H&N with nil node: good prognosis ~80% 5yr survival; node +ve ~20%; surgery
![Page 18: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/18.jpg)
IHC
Retinoblastoma NSE, GFAP, (Synaptophysin) SYN, NF
Medulloblastoma NSE, GFAP, SYN, S100
Neuroblastoma CD99 & GFAP–ve; NSE, Protein gene product (PGP) 9.5, VIP, Chromogranin, SYN, weak catecholamine +ve ; NB-84
Ewing’s/ PNET NSE, GFAP, SYN, CD99, Leu-7, PGP 9.5, Chromogranin, HMB 45, NF
Paraganglioma NSE, Leu/ Met –enkephalin, somatostatin, VIP, subst P, ACTH, Calcitonin, Neurotensin
Small Cell Carcinoma of Lung
NSE, SYN, cytokeratins, EMA, chromogranin
Merkel Cell Carcinoma
NSE, SYN, Low mol wt CK (ck20); CrA, NCAM, Map2; CD99
![Page 19: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/19.jpg)
A: Retinoblastoma
B: Medulloblastoma
C: Neuroblastoma
A B
C
![Page 20: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/20.jpg)
PARAGANGLIOMA
SMALL CELL CARCINOMA MCC
![Page 21: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/21.jpg)
Ewing’s Sarcoma/ PNET Ewing’s
• Age <30• Site: paravertebral
region, chest• H/P:
– Uniform, round cells– Fine chromatin– Pin-point nucleoli– Abundant glycogen– Rosettes absent
CD99 positive & CD45 negative
PNET• Age - <25• Site: U/ L extremities-
upper thighs, shoulder• H/P:
– Irregular cells– Coarse chromatin– Prominent nucleoli– Scant glycogen– HW rosettes;
sometimes FW
![Page 22: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/22.jpg)
PNET EWING’s SARCOMA
![Page 23: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/23.jpg)
Rhabdomyosarcoma
Most common soft tissue tumor in children
Histological classification:
Modified Horn and Enterline classification:
○ Embryonal (ERMS)
Botryoid
○ Alveolar (ARMS)
○ Pleomorphic
○ Other
![Page 24: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/24.jpg)
Age: infants, children
Embryonal type: 8 yrs
Alveolar type: 16 yrs
M > F (1.3:1.0);
Alveolar type: M=F
Sites:
Head and neck: orbit, nasal cavity, palate, mouth,
pharynx/ nasopharynx
Trunk
Extremities
![Page 25: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/25.jpg)
Deep-seated, rapid enlargement, symptoms sec.
to pressure effect, no bony erosion
Metastases: lung, lymph node, bone marrow,
heart, brain, pancreas, liver, kidney
![Page 26: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/26.jpg)
Embryonal Rhabdomyosarcoma
A type having alternating loosely cellular areas with
myxoid stroma and densely cellular areas with spindle
cells, seen mainly in infants and small children.
Resemble embryogenesis of skeletal muscle
Varying degrees cellularity; Myxoid matrix
Small, undifferentiated, hyperchromatic round or spindle
cells
Rhabdomyoblasts:
Strap/ ribbon/ tadpole shaped; ‘broken-straw’ pattern
One or two nuclei; prominent nucleoli
Cross-striations
![Page 27: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/27.jpg)
Spider cells’ – i/c glycogen – multivacuolated cells
Cartilaginous differentiation - genitourinary tract and peritoneal
Botryoid type:
A type of cancer that arises from rhabdomyoblasts which are
immature muscle cells. The tumors can occur arise from muscle
tissue almost anywhere in the body but in the Botryoid form, tends
to hollow organs with a mucosal lining such as the bladder, uterus
and vagina. Symptoms depend on size and location of the tumor.
Symptoms:
Asymptomatic
Vaginal lump
![Page 28: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/28.jpg)
Polypoid growth Mucosal cavities
Sites: vagina cervix urinary bladder nasopharynx biliary tract
HistopathologyHypocellular with mucoid stroma, cambium layer
D/D – Pelvic neuroblastoma Burkitt Lymphoma
![Page 29: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/29.jpg)
BOTRYOID TYPEERMS
Varying degrees cellularity; Myxoid matrix, Small, undifferentiated, hyperchromatic round or spindle cells, Rhabdomyoblasts are Strap/ ribbon/ tadpole shaped; ‘broken-straw’ pattern, One or two nuclei; prominent nucleoli
Immature muscle cells, Hypocellular with mucoid stroma, cambium layer
![Page 30: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/30.jpg)
Alveolar Rhabdomyosarcoma
A type having dense proliferations of small round cells
among fibrous septa that form alveoli, seen mainly in
adolescents and young adults.
Ill-defined aggregates – round or oval cells
Central loss of cohesion – ‘alveolar spaces’
Dense fibrous septae.
‘solid’ type – at periphery; active stage of tumor
Clear-cell rhabdomyosarcoma
Rhabdomyoblasts uncommon
Multinucleated giant cells
![Page 31: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/31.jpg)
ALVEOLAR RHABDOMYOSARCOMA
Dense proliferations of small round cells among fibrous septa, round or oval cells, Dense fibrous septae, Multinucleated giant cells, Rhabdomyoblasts uncommon
![Page 32: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/32.jpg)
Special stains:
Not routinely used
Trichrome
PTAH (Phosphotungustic acid hematoxylin)
PAS
IHC:
desmin, muscle-specific actin, myoglobin, MyoD1; CD99
Prognosis:
Favourable: younger age, orbital location, small size, botryoid
type, nil lymph node metastases
Unfavourable: adults, non-orbital H&N/ abdomen, large size,
alveolar type (PAX3/FKHR), parameningeal site, lymph node
metastases
![Page 33: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/33.jpg)
Pleomorphic Rhabdomyosarcoma A type having large cells with bizarre hyperchromatic
nuclei, seen in the skeletal muscles, usually in the limbs of
adults.
Historically, Stout first introduced pleomorphic
rhabdomyosarcoma (PRMS) into the literature in 1946 as
"classical" rhabdomyosarcoma
In 1958, Horn and Enterline outlined four subtypes of
rhabdomyosarcoma and called the classical ones
"pleomorphic rhabdomyosarcoma.“
It is an aggressive sarcoma.
Arises predominantly in the extremities of adult males with
a mean age of 49 years.
![Page 34: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/34.jpg)
Pleomorphic rhabdomyosarcoma (classic variant; left) and diffusely positive desmin reactivity (right; A); myoglobin positivity (B); MyoD1 (nuclear, left) and fast myosin (cytoplasmic, BI) positivity (C); and myogenins myf 3 (nuclear, left) and myf4 (nuclear, BI) positivity (D).
![Page 35: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/35.jpg)
According to Mary A Furlong (2001) et al. there are 3 morphologic
variants:
Type I or "classic PRMS" is defined morphologically by sheets of
large, atypical polygonal, pleomorphic rhabdomyoblasts (PRMB).
Type II, also termed "round cell PRMS," was composed
morphologically of these large PRMB among medium sized slightly
pleomorphic round rhabdomyoblasts.
Although one may consider this morphologic variant to have
similarities to embryonal rhabdomyosarcoma, there are several
reasons why these cases are better classified as the round cell variant
of pleomorphic rhabdomyosarcoma. These tumors are all in adults.
The round cells are larger than the round cells of embryonal
rhabdomyosarcoma, and there are more numerous and more atypical
pleomorphic rhabdomyoblasts within these tumors.
![Page 36: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/36.jpg)
Type 1 (classic variant) pleomorphic rhabdomyosarcoma, with sheets of atypical, bizarre, large, polygonal pleomorphic rhabdomyoblasts with abundant eosinophilic cytoplasm
Type 2 (round-cell variant) pleomorphic rhabdomyosarcoma, with scattered pleomorphic rhabdomyoblasts among a background of medium sized, slightly angulated round-to-epithelioid rhabdomyoblasts (A).
Higher magnification of this variant (B, left); note the geographic necrosis (common to all morphologic variants; B, right).
![Page 37: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/37.jpg)
Type 3 (spindle cell variant) pleomorphic rhabdomyosarcoma, with scattered large polygonal pleomorphic rhabdomyoblasts and a spindled, storiform background of rhabdomyoblasts (A–B, left); the atypia, atypical mitoses, and bizarre giant cells are common to all variants (B, right).
![Page 38: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/38.jpg)
Solid alveolar rhabdomyosarcoma subtype can be
distinguished from this round cell variant of PRMS by its
t(2;13) or variant t(1;13) chromosomal translocations
Type III, or spindle cell PRMS, was composed of large,
atypical pleomorphic rhabdomyoblasts with highly spindled
and often storiform backgrounds.
Histopathology
They are composed of large, atypical, polygonal
pleomorphic rhabdomyoblasts with abundant eosinophilic
cytoplasm.
![Page 39: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/39.jpg)
These large rhabdomyoblasts are often arranged in clusters,
sheets, or scattered individual cells.
Atypical, vesicular nuclei with prominent nucleoli predominate.
The rhabdomyoblasts in the background that surround the large,
pleomorphic rhabdomyoblasts vary from round to spindled.
Immunohistochemistry
Immunohistochemical antibodies were applied to these tumors
in the early 1980s, predominantly using myoglobin, desmin,
creatinine kinase subunit M, and various actins to detect
skeletal muscle differentiation.
In 1993, fast myosin, a skeletal muscle-specific marker, was
added to the repertoire for PRMS
![Page 40: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/40.jpg)
MyoD1 was applied in 1995
Myf4, a skeletal muscle-specific myogenin, has only been
studied on four cases of PRMS in the literature
Differential Diagnosis:
Malignant fibrous histiocytoma (MFH) - Occasionally
express both desmin and MSA. But should not express other
specific skeletal muscle markers, such as MyoD1, fast skeletal
muscle myosin, myf4, or myoglobin.
Pleomorphic leiomyosarcoma - a myoid tumor with
desmin expression, morphologically has intersecting fascicles,
lacks the presence of large polygonal rhabdomyoblasts, and
also does not express skeletal muscle specific markers.
![Page 41: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/41.jpg)
Small Cell Osteosarcoma
First described 1979 (Sim et al) 1.3% of osteosarcoamas Location:
Usually long bones Rarely simultaneous multiple bone involvement Pulmonary metastases – common
Symptoms: Pain Swelling Neurological symptoms due to pressure effects
X-ray: Intra-medullary lytic bone lesion; peripheral
sclerosis
![Page 42: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/42.jpg)
Histopathology:
Round to oval cells
Nuclei
○ Varied nuclear size
○ Hyperchromatic
○ Prominent/ absent nucleoli
○ Coarse chromatin
Glycogen in cells
Multinucleated giant cells
Stroma:
○ Dense fibrous or myxoid or mixed
○ Osteoid production – ‘lace-like’ or hemangio-pericytomatous
![Page 43: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/43.jpg)
Immunohistochemistry:
Osteonectin and osteocalcin positivity
Ultrastructural findings:
Precalcification stage seen as flocculent
extracellular material
Prognosis:
Low-grade >90% survival (5yrs)
Lung metastases ~30% survival (5yrs)
![Page 44: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/44.jpg)
Mesenchymal Chondrosarcoma
First described 1959 – Lictenstein and Bernstein
Clinical features:Young adults – 15 to 35 yrs.Site:
○ Head and neck: orbit, dura mater, occiput○ Lower extremities: thigh○ Pleura, peritoneum
Painless, slowly enlarging masses
X-rays:Soft tissue mass with radiopaque flecks or
streaks
![Page 45: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/45.jpg)
Pathologic findings:
Sheets of round or oval cells and nodules of
cartilage
Cells:
○ Hyperchromatic nuclei
○ Scant cytoplasm
○ Hemagiopericytomatous pattern
Blending of islands of cartilage with cellular
areas
![Page 46: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/46.jpg)
MESENCHYMAL CHONDROSARCOMA
![Page 47: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/47.jpg)
IHC:
+ve : S100, NSE, Leu-7, CD99
-ve : desmin, actin, cytokeratin
Prognosis:
5 year survival rate 54.6%
Early metastases – lung
![Page 48: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/48.jpg)
Round Cell Liposarcoma
Liposarcoma : most common sarcoma among
adults
Spectrum: myxoid and round cell liposarcoma
Myxoid/ round cell types – 50%
Clinical features:
5th decade
Site: thigh, popliteal region
![Page 49: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/49.jpg)
Histopathology:Myxoid type:
○ Low cellularity; round/ fusiform cells; lipoblasts○ Myxoid matrix – hyaluronic acid○ Haemorrhage, cartilaginous, osseous,
leiomyomatous fociRound cell type:
○ Loss of differentiation from myxoid type○ Sheets of primitive round cells
as a foci in the myxoid type or pure round cell type
○ High nuclear/cytoplasmic ratio○ No intervening myxoid stroma○ Occasional lipoblast: multi- or uni- vacuolar
cells
![Page 50: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/50.jpg)
ROUND CELL LIPOSARCOMA
![Page 51: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/51.jpg)
Cytogenetics and molecular studies:
Reciprocal translocation t(12;16)(q13;p11)
CHOP-TLS – 3 types fusion transcripts
○ Type II identified in myxoid/ round cell type
○ Unresponsive to adipogenic stimulation
○ Loss of contact inhibition
Prognosis:
Depends on % of round cell population
>25% RC = metastasis to lung, bone, soft tissues
and poor prognosis
![Page 52: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/52.jpg)
Desmoplastic small round cell tumor Multiphenotypic differentiation
Malignant soft tissue tumors of uncertain type
Uncommon
Clinical features:
Age: 15 to 35 yrs; any age
M:F = 4:1
Site: abdominal or pelvic
Complaints: pain, distension and constipation
![Page 53: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/53.jpg)
Histopathology:Nests of small round/ oval cellsCells:
○ Hyperchromatic nuclei○ Scant cytoplasm○ Few cells – paranuclear hyaline inclusion
- intermediate filament○ Rare – signet cells○ Occasional nuclear atypia
Cellular arrangement:○ Large nests – central necrosis○ Tubular○ Zellballen○ Cords
Abundant fibrous connective tissue stroma
![Page 54: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/54.jpg)
DESMOPLASTIC SMALL ROUND CELL TUMOR
![Page 55: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/55.jpg)
IHC:Cytokeratin and EMA ~100%Myogenic antigens
○ Desmin 90% - perinuclear dot-like staining○ MyoD1 –ve
Neural antigens:○ NSE ~82%○ Leu-7 ~49%○ CD99 ~34%○ NB84 ~50%
CA-125 +ve; a mucinous glucoprotein also seen in ovarian carcinomas and breast adenocarcinomas
![Page 56: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/56.jpg)
Cytogenetics:
Translocation t(11;22)(p13;q12)
EWS-WT1 fusion transcript
Transcript induces PDGF – mitogenic
Poor prognosis
![Page 57: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/57.jpg)
Wilm’s tumor Also called nephroblastoma. Is cancer of kidneys. Typically occurs in children, rarely in adults. First described by Dr. Max Wilms, german surgeon
(1867 - 1918). Malignant tumor containing metanephric blastema,
stromal and epithelial derivatives. Presence of abortive tubules and glomeruli
surrounded by spindled cell stroma is the characteristic feature.
Mesenchymal component may include cells showing rhabdomyoid differentiation. (malignancy – rhabdomyosarcomatous Wilms)
![Page 58: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/58.jpg)
Clinical Features:• Abnormally large abdomen• Abdominal pain• Fever• Nausea and vomiting• Blood in the urine• High B.P. in some cases
Histopathology:May be separated into 2 prognostic groups based on pathological characteristics.
• Favorable – Contains well developed components mentioned above.
• Anaplastic – Contains diffuse Anaplasia (poorly developed cells)
![Page 59: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/59.jpg)
• Malignant small round (blue) cells – 2x the size of resting lymphocyte (blastema component)
• Tubular structures/ rosettes (epithelial component)• Loose paucicellular stroma with spindle cells (stromal
component)
![Page 60: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/60.jpg)
![Page 61: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/61.jpg)
Synovial Sarcomaa
Uncertain histogenesis
Microscopic resemblance to developing synovium
Clinical features:
Age: 15 to 40 years
M:F = 1.2:1
Complaints:
Deep-seated swelling; pain or tenderness
Functional disturbance – poorly differentiated type
h/o trauma
![Page 62: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/62.jpg)
Site: Lower extremities > upper extremities > head and neck
> trunk Head and neck: neck, pharynx, larynx
X-ray: Superficial bone erosion Multiple, small, spotty radiopacities
Histopathology: Histological subtypes:
○ Biphasic type: Epithelial and spindle cell morphologies
○ Monophasic type:Fibrous type, i.e. spindle cell typeEpithelial type
○ Poorly differentiated round cell type
![Page 63: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/63.jpg)
Poorly differentiated round cell type:
3 types:
○ Large cell
○ Small round cell
○ Spindle cell
Rich vascularity; thin walled vessels
Intra-cytoplasmic hyaline inclusions
![Page 64: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/64.jpg)
POORLY DIFFERENTIATED SYNOVIAL SARCOMA
![Page 65: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/65.jpg)
IHC:
CK and EMA usually +ve; but –ve in round cell type
S100 +ve
CD99 +ve
CD34 –ve
Cytogenetics:
Reciprocal translocation t(X;18)(p11;q11)
SYT-SSX1/ SSX2
Poorly differntiated type associated with poor
prognosis
![Page 66: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/66.jpg)
Differential DiagnosisEwing’s Sarcoma/ PNET
Neuroblastoma
ARMS
Urinary catecholamine
CD99 -ve
Alveolar pattern Rhabdomyoblasts MyoD1
![Page 67: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/67.jpg)
Metastatic Small Cell Carcinoma -
Lung
Older age Radiograph – lung
involvement
Merkel Cell Carcinoma
Older age CD99 -ve
Differential DiagnosisEwing’s Sarcoma/ PNET
![Page 68: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/68.jpg)
Differential DiagnosisEwing’s Sarcoma/ PNET
Mesenchymal Chondrosarcoma
Presence of cartilage
Absence of cartilage Dx difficult; similar IHC
Small Cell Osteosarcoma
Presence of osteoid
Similar IHC
![Page 69: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/69.jpg)
Differential Diagnosis
Poorly Differentiated
Synovial Sarcoma
Round cells arranged around hemangio-pericytoma like vasculature
IHC similar
DSRCT Young adults; males Dense fibrous stroma Polyphenotypic
profile
Ewing’s Sarcoma/ PNET
![Page 70: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/70.jpg)
Differential DiagnosisEwing’s Sarcoma/ PNET
Non-Hodgkin’s Lymphoma
Absence of glycogen
Lymph node involvement – rare in ES/ PNET
![Page 71: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/71.jpg)
Differential Diagnosis
Rhabdomyoblasts Poorly differentiated angiosarcomas
Small cell carcinomas
Melanoma ES/PNET group
Rhabdomyosarcoma
PAS-diastase digestion
Melanoma Synovial Sarcoma Lymphoma
![Page 72: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/72.jpg)
Differential DiagnosisRhabdomyosarcoma
MyoD1 Neuroectodermal tumors
Leiyomyosarcoma Melanoma Lymphoma Synovial Sarcoma Small Cell Carcinoma
![Page 73: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/73.jpg)
The EWS gene• Location: 22q12
• EWS codes - nuclear protein; unknown function
Ewing’s Sarcoma– EWS translocation with ETS group of transcription factors
• FLI1 (11q24)
• ERG (21q22)
• ETV (7p22)
• E1AF (17q12)
– ETS group regulate expression of various genes; regulate epithelial-mesenchymal interactions; oncogenesis – can activate MMP’s
– EWS/ETS fusion transcript – telomerase activity in Ewing’s sarcoma
![Page 74: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/74.jpg)
DSRCT WT1 – tumor supressor geneIn DSRCT – poor prognosis; fusion transcript
potent mitogen
Myxoid LiposarcomaRare fusionGood response to chemotherapy, rapid
recurrence and very primitive round cells
![Page 75: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/75.jpg)
Extraskeletal myxoid chondrosarcoma
EWS/TEC [t(22;9)(q12;q22)]
TEC - tyrosine kinase gene family
WS/TEC transcript – oncogenic; activation
of transcription of target genes involved
in cell proliferation.
![Page 76: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/76.jpg)
Round cell tumor of Hematolymphoid Origin
Lymphoma
Malignant neoplasms resembling stage of normal
lymphocyte differentiation
Hodgkin’s and Non-Hodgkin’s type
Primary Lymphoma of Bone
Hodgkin’s lymphoma:
○ ~100% nodal
○ Reed-Sternberg cells
![Page 77: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/77.jpg)
Non Hodgkin’s Lymphoma:67% nodal and 33% extra nodalB cell, T cell/ NK cell neoplasms
Burkitt’s lymphoma childhood., rare- adults -Maxilla, mandible African –swelling of infected jaw -Loosing of teeth -Lymphadenopathy -Sporadic- abdominal tumors
![Page 78: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/78.jpg)
Primary Lymphoma of bone Identified in 1939 by Parker and Jackson
Termed Reticulum Cell Lymphosarcoma by James
Ewing
Primary Lymphoma of Bone – 1963 by Ivins and Dahlin
94% NHL and 6% HL
Clinical features:Age: 2nd to 8th decadesM:F = 1.5:2.1Complaints: swelling and pain
![Page 79: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/79.jpg)
Diagnostic criteria:
Primary bone focus
Histologic confirmation
No evidence of nodal of soft tissue involvement
at time of presentation
X-ray:
Lytic bone lesion
Periosteal reaction
osteomyelitis
![Page 80: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/80.jpg)
Histopathology:
Non-Hodgkin's lymphoma
○ Large round cells
○ Irregular cleaved nuclei and prominent nucleoli
○ Reticulin fibers.
○ Commonest subtype is diffuse histiocytic lymphoma.
Hodgkin's lymphoma
○ plasma cells, lymphocytes, histiocytes and
eosinophils. Reed-Sternberg cells
![Page 81: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/81.jpg)
Burkitt’s lymphoma:Histopathology: B-cell proliferation- diffuse pattern-Burkitt cells-Starry sky appearance
Immunohistochemistry:
Non Hodgkin’s lymphoma : Positive: Cyclin D1, CD5, CD43, CD20, CD45. Negative: CD23.
Hodgkin’s lymphoma:CD45-, CD30+, CD15+/-
![Page 82: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/82.jpg)
Burkitts lymphoma:Mature B-cells- CD 10 & surface immunoglbulinGenerally strongly express markers of B cell
differentiation (CD20, CD22, CD19) as well as CD10, and BCL6. The tumour cells are generally negative for BCL2 and TdT. The high mitotic activity of Burkitt lymphoma is confirmed by nearly 100% of the cells staining positive for Ki67.[
Causative organism:EBV, HIV
![Page 83: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/83.jpg)
Hodgkin’s lymphoma - mixed cellularity type.
![Page 84: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/84.jpg)
Burkitts lymphoma - medium size lymphoid cells, starry sky" appearance - due to scattered tingible body-laden macrophages. Tumor cells possess small amount of basophilic cytoplasm. The cellular outline usually appears squared off.
Non Hodgkin’s lymphoma - Monomorphic small lymphoid cells less than twice the size of a resting lymphocyte, Abundant mitoses.Sclerosed blood vessels.Scattered epithelioid histiocytes.
![Page 85: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/85.jpg)
References
1. Sharon W. Weiss and John R. Goldblum. Enzinger and
Weiss’s Soft Tissue Tumors. Mosby; Fourth Edition.
2. Kumar, Abbas and Fausto. Robbins and Cotran Pathologic
Basis of Disease. Elsevier, Seventh Edition.
3. Douglas R. Gnepp. Diagnostic Surgical Pathology of the
Head and Neck. W. B. Saunder’s; 2000.
4. Dyer and Bremner.The Search For The Retinoblastoma Cell
Of Origin. Nature Reviews Cancer 2005;5: 91-101.
5. Mc Manus et al. The molecular pathology of small round-
cell tumours-relevance to Diagnosis, prognosis, and
classification. Journal of pathology 1996; 178: 116-121.
![Page 86: Round Cell Tumors Final](https://reader035.vdocuments.us/reader035/viewer/2022062219/5540f0ab55034691638b4567/html5/thumbnails/86.jpg)
6. Nakajima et al.Small Cell Osteosarcoma of Bone - Review of 72 cases.
Cancer 1997;79:2095–106
7. Pinkerton et al. Small Round Cell Tumors of Childhood. The Lancet
1994; 344: 725-29
8. Stein et al. Primary Lymphoma of Bone - A Retrospective Study.
Oncology 2003;64:322-327
9. Gregorio A, Corrias MV, Castriconi R, et al. (July 2008).
"Small round blue cell tumours
: diagnostic and prognostic usefulness of the expression of B7-H3 surfac
e molecule"
. Histopathology 53 (1): 73–80.
10. Mary A Furlong M.D., Thomas Mentzel M.D. and Julie C Fanburg-
Smith M.D. Pleomorphic Rhabdomyosarcoma in Adults: A
Clinicopathologic Study of 38 Cases with Emphasis on Morphologic
Variants and Recent Skeletal Muscle-Specific Markers. Mod Pathol
2001;14(6):595–603