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Epithelial and mesenchymal tumors of uterine corpus
Prakriti GuptaDNB Pathology
Sir Gangaram Hospital, New Delhi
1. Epithelial tumors and related lesions2. Mesenchymal tumors3. Mixed epithelial and mesenchymal4. Gestational trophoblastic tumors5. Miscellaneous tumors6. Hematopoetic and lymphoid tumors
Epithelial tumors and related lesions Endometrial carcinoma Endometroid carcinoma• Villoglandular• Secretory • Ciliated• Variant with squamous differentiation Mucinous Serous Mixed Transitional Squamous Small cell Undifferentiated
Endometrial hyperplasiaNon atypical• Simple• ComplexAtypical• Simple • ComplexEndometrial polypTamoxifen related changes
Mesenchymal tumorsEndometrial stromal tumors
• Endometrial stromal nodule • Endometrial stromal sarcoma, low grade • Undifferentiated endometrial sarcoma
Smooth muscle tumours Leiomyoma, not otherwise specified Histological variants• Mitotically active variant• Cellular variant • Haemorrhagic cellular variant• Epithelioid variant • Myxoid • Atypical variant • Lipoleiomyoma variant
Smooth muscle tumour of uncertain malignant potential Leiomyosarcoma • Epithelioid variant • Myxoid variant
Growth pattern variants• Diffuse leiomyomatosis• Dissectiing leiomyoma• Intravenous leiomyomatosis • Metastasizing leiomyoma Miscellaneous mesenchymal tumours
Mixed endometrial stromal and smooth muscle tumour• Perivascular epithelioid cell tumour• Adenomatoid tumour • Other malignant mesenchymal tumours• Other benign mesenchymal tumours
Mixed epithelial and mesenchymal tumours• Carcinosarcoma (malignant müllerian mixed
tumour; • metaplastic carcinoma) • Adenosarcoma • Carcinofibroma • Adenofibroma • Adenomyoma Atypical polypoid variant
Gestational trophoblastic disease
Trophoblastic neoplasms• Choriocarcinoma • Placental site trophoblastic tumour • Epithelioid trophoblastic tumour Molar pregnancies• Hydatidiform mole • Complete• Partial • Invasive • Metastatic Non-neoplastic, non-molar trophoblastic lesions• Placental site nodule and plaque• Exaggerated placental site
Miscellaneous tumours• Sex cord-like tumours• Neuroectodermal tumours• Melanotic paraganglioma• Tumours of germ cell type• Others
Lymphoid and haematopoetic tumours• Malignant lymphoma (specify type)• Leukaemia (specify type)
Secondary tumours
Endometrium
• The endometrium and the myometrium are of mesodermal origin
Classification of endometrial hyperplasia
Hyperplasia without atypia• Simple hyperplasia without atypia• Complex hyperplasia without atypia
Atypical hyperplasia• Simple atypical hyperplasia (very rare)• Complex atypical hyperplasia
Stroma Atypical endometrial hyperplasia
Well differentiated endometrial carcinoma
Altered fibroblastic Stroma (desmoplastic response
unaltered, same as that of normal endometrium
parallel, densely arranged fibroblasts with more fibrosis than normal endometrial stroma, that disrupts the usual glandular pattern
Stromal cells Basophilic ,naked nuclei appearance
spindle , eosinophilic, wavy
Confluent glandular aggregates without interveningstroma reflect stromal invasion
Complex papillary patterns represent stromal invasionif multiple, branching, fibrous processes lined by epithelium
are present
Tamoxifen related changes
• Enlarged uterus• Endometrial cysts• Polyps – large, sessile, wide base, honeycomb • Bizzare stellate glands• Epithelial and mesenchymal metaplasias• Periglandular stromal condensation ( cambium
layer)• Malignancy – 3%
Endometrial carcinoma
Endometrioid adenocarcinoma• Villoglandular• Secretory• Ciliated cell• Endometrioid adenocarcinoma with squamous differentiation
Serous carcinomaClear cell carcinomaMucinous carcinomaSquamous carcinomaMixed types of carcinomaUndifferentiated carcinoma
Modified World Health Organization and International Society ofGynecological Pathologists Histologic Classification of
Endometrial carcinoma
Feature Type I Type II
Unopposedestrogen
Present Absent
Menopausal status Pre- andperimenopausal
Postmenopausal
Precursor lesion Atypicalhyperplasia
Endometrialintraepithelialcarcinoma
Tumor grade Low High
Myometrialinvasion
Variable, often minimal Variable, oftendeep
Histologicsubtypes
Endometrioid Serous and clear cell
Behavior Indolent Aggressive
Genetic alterations PTEN mutation MicrosatelliteinstabilityK-ras mutation
P53 mutation
incidence 80-85% 10-15%
Endometrioid adenocarcinoma
Glandular or villoglandular structures lined by simple to pseudostratified columnar cells.
As the glandular differentiation decreases and is replaced by solid nests and sheets of cells, the tumour is classified as less well differentiated (higher grade).
Nuclear grade1 nuclei are oval, mildly enlarged,
and have evenly dispersed chromatin
2 Intermediate between 1 and 33 nuclei are markedly enlarged
and pleomorphic, with irregular coarse chromatin,and prominent eosinophilic nucleoli
• Grade 1: 5% non-squamous, non-morular growth pattern• Grade 2: 6-50% non-squamous, non-morular growth pattern• Grade 3: > 50% non-squamous, non-morular growth pattern Note: Squamous/morular components are excluded from grading. Bizarre nuclear atypia should raise the grade by one (i.e. from 1 to 2 or 2 to 3) but may also signify type II
differentiation.
Architectural grade
1 No more than 5% of the tumor is composed of solid masses
2 6–50% of the tumor is composed of solid masses
3 More than 50% of the tumor is composed of solid masses
Villoglandular
Thin, delicate fronds covered by stratified columnar epithelial cells with oval nuclei that generally display mild to moderate (grade 1 or 2) atypia
D/D serous
Secretoryprogestin treatment
Well differentiated glandular pattern
columnar cells, unstratified
subnuclear or supranuclear vacuolization closely resembling day 17–22 secretory endometrium
nuclei are grade 1.
corpus luteum
D/D clear cell
With Squamous differentiation<10% squamous element
Both the glandular and squamous components display grade 2 or 3 nuclear atypia
an increased nuclear cytoplasmicratio
increased mitotic activity
Graded on the basis of glandular component
D/D atypical hyperplasia with squamous metaplasia
Mucinous
Epithelial cells lining the glandsColumnar cells with minimal stratification.Cystically dilated glands filledwith mucin and papillary fronds surrounded by extracellular lakes of mucin, containing neutrophils
Serous complex papillary architecture
short and densely fibrotic or thin and delicate
Cells are cuboidal orhobnail shaped and contain abundant granular eosinophilic or clear cytoplasm
Loosely cohesive marked cytologic atypia nuclear pleomorphism,hyperchromasia, and macronucleoli
Clear cellSolid- masses of clear cells with eosinophiliccells
papillary, tubular and cystic -hobnail-shaped cells with interspersed clear and eosinophilic cells.
Moderate to marked atypia
PAS-positive, diastase resistantintracellular, and extracellular hyaline bodies
Endometroid Serous Clear cell
ER + - -
PR + - -
P53 -/+ + -
P16 - + -
Napsin A - - +
HNF-1 β - - +
Endometrial stromal tumors
Endometrial stromal nodule
Endometrial stromal sarcoma, low grade
Undifferentiated stromal sarcoma
Nature benign Malignant, low grade
Malignant, high grade
age 23-75 , 1/3 rd postmenopausal
42-58, 1/4th premenopausal
55-60
gross Solitary, well deliniated , yellow tan nodule of 0.8 -15 cm. Purely intramural, protrusions upto 3mm
Solitary well deliniated intramural with extensive permeation of myometrium upto serosa
Polypoid , fleshy, grey endometrial mass with hemmorhage and necrosis
Endometrial stromal nodule
ESS, low grade Undifferentiated sarcoma
histology Resemble proliferative phase endometriun supported by a large no. Of thin walled arterioles
Spindled stromal cells in plexiform pattern with a rich network of arterioles infiltrating myometrium
markedly pleomorphic cells with No plexiform pattern or vascular network displacing myometrium
Epitheliod, smooth muscle and sex cord like differentiation
present present absent
Extrauterine extent
absent Cord like in 1/3rd Worm like in vessels of broad ligament and adnexa
Distant metastasis at presentation
Ususal mitosis <3 <3 >10
ESN ESS, low grade
Undifferentiated sarcoma
Somatic genetics
Diploid, low S-fraction
Diploid, low S-fraction
Aneuploid, S-fraction>10%
molecular t(7;17)(p15;q21) JAZF1 - JJAZ1 fusion
t(7;17)(p15;q21) JAZF1 - JJAZ1 fusion
+/-
vimentin + + +/-CD10 + + -ER, PR + + -Desmin and h-caldesmon
-/+ -/+ -
Nuclear B-cateninNuclear WT-1
++
-+
--
ESN with sex cord differentiation
Smooth muscle tumors
Smooth muscle tumours Leiomyoma, not otherwise specified Histological variants• Mitotically active variant• Cellular variant • Haemorrhagic cellular variant• Epithelioid variant • Myxoid • Atypical variant • Lipoleiomyoma variant
Smooth muscle tumour of uncertain malignant potential Leiomyosarcoma • Epithelioid variant • Myxoid variant
Mitotically active leiomyoma
>5 MF/ 10 hpf
If
15 MF/ 10 hpf
Mitotically activeLeiomyoma with limited experience
Cellular
• Cellularity is ‘‘significantly’’ greater than the surrounding myometrium
• < 5% of leiomyomas
Hemorrhagic cellular
Multifocal stellatehemorrhages cellular and containspatchy areas ofhemorrhage and edema. MF mainly within a narrow zone resemblinggranulation tissue around areas of hemorrhage
Atypical leiomyoma• progestins • moderate to severe
cytologic atypia• enlarged
hyperchromatic nuclei with prominent chromatin clumping and smudging
• Large cytoplasmic pseudonuclear inclusions
• Multinucleated tumor giant cells
• 0–4 MF/10 HPF• No tumor necrosis
Epitheloid• Cells are round or
polygonal• Clusters or cords• nuclei are round,
relatively large centrally positioned. There are three basic subtypes Leiomyoblastomaclear cell leiomyoma plexiform leiomyoma
Growth pattern variants
Dissecting Leiomyoma
Benign smooth muscle proliferation with a border marked by the dissection ofcompressive tongues of smooth muscle into the surrounding myometrium and, occasionally, into the broad ligament and pelvis
Intravenous Leiomyomatosis andLeiomyoma with Vascular Invasion
Nodular masses of histologically benign smooth muscle cells growing within venous channels• growth
extends into the vena cava in >10% of patients
Benign Metastasizing Leiomyoma
‘‘Metastatic’’ smooth muscle tumor deposits inthe lung, lymph nodes, or abdomen appear to be derived from a benign leiomyoma of the uterus.MC- Lungs
Disseminated PeritonealLeiomyomatosis
Multiple smooth muscle, myofibroblastic, and fibroblastic nodules on the peritoneal surfacesof the pelvic and abdominal cavities in women of reproductive ageAssociated with pregnancy,granulosa tumororal contraceptive use
Tumor cell necrosis
Cellular atypia mitosis
leiomyoma -
-
None to mild
Diffuse moderate to severeAtypical leiomyoma with low risk of recurrence
< 5≥ 5Mitotically active leiomyoma
STUMP -
-
+
Focal moderate to severe
Diffuse moderate to severeMild
≥5
5-9 atypical MF
<10
Leiomyosarcma(smooth muscle diff)
+
+
Mild
Diffuse moderate to severe
≥ 10
Any level
Myxoid
Epitheloid
leiomyoma leiomyosarcoma
SMA + +
Desmin + +
CD 10 - +/-
PR + -
p16 - +
P53 - +
Ki 67 -/+ +++
Smooth muscle tumorsvs
Stromal tumors
cellular leiomyoma vs ESN
IV TUMOR
IV leiomyoma vs ESS, low grade
Cells
Vasularity
reticulin
Stromal tumors
SmallerLess cytoplasm
Numerous arterioles ( plexiform)
Around individual cells
Smooth muscle tumorsLargerMore cytoplasm
Thick walled vessels
Parallels the fascicles of cells
SMA 0 to ++ ++ to +++
Desmin 0 to + +++
Caldesmon 0 +++
CD 10 + to +++ 0 to +
Mixed epithelial and mesenchymal tumors
Benign epithelium
Malignant epithelium
Benign mesenchyme
AdenofibromaAdenomyoma ( including atypical)
carcinofibroma
Malignant mesenchyme
adenosarcoma carcinosarcoma
Adenofibroma
Adenomyoma
Adenosarcoma
Carcinofibroma
Carcinosarcoma
clinical
Uncommon
elderly
Atypical-premenopausal
15-90yrsIrradiationtamoxifen
uncommon
Postmenopausal Pelvic irradiationtamoxifen
gross Fibrous polyps with cystic spaces
PoypoidalSubmucosalLower uterine segment and upper endocervix
PolypoidFoci of necrosis and hemorrhage--/+ myometrial invasion
Polypoid bulkyNecrosisHemmorrhage Myometrial invasion
Adenofibroma Adenomyoma Adenosarcoma
Carcinofibroma
Carcinosarcoma
histo Club like or papillary lined by epitheliumFibromatous stroma
Benign endometrial gland s in fibromyomatous stroma
Atypical- distorted glands with marked architectural complexityno endometrial stroma around the glandsInterlacing fascicles of benign smooth muscle
leaf like growth like phyllodesMitosis >1/10hpfStromal hypercellularityPeriglandular stromal cuffingAtypia
HomologousHeterologous -10-15%
Epithelial- glandularNon glandular
MesenchymalHomologous-Udiif sarcomaLeiomyosarcomaESS
Heterologous- chondrosarcomarhabdomyosarcoma
Adenofibroma
Adenosarcoma
Periglandular stromal hypercellularity in adenosarcoma
Carcinosarcoma
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