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Ovary-Gross & Microscopy
Presenter: Dr Himachal Mishra
Moderator: Dr Shwetha Patil
Assistant Professor, Department of Pathology
Outline
• Normal Structure
• Grossing Techniques
• Non Neoplastic lesions
• WHO Classification of Ovarian Tumors
• Recent changes in WHO Classification
• Approach to Neoplastic lesions
• Neoplastic lesions
• Summary
• References
Structure of the ovary
Grossing Techniques
• Measurement in 3 D and weight
• External surface-smooth or irregular, adhesions, rupture, etc.
Cut surface
• Capsule – thickened or normal, adhesions, hemorrhage, rupture, etc;
• Cortex and Medulla, cysts—location and number,
corpus luteum, appearance, calcification.
papillary structures
nature of contents -colour of contents
• Section along the maximum diameter of the ovary.
Bits
H – One bit routinely to include cortex
and medulla & adjacent cyst wall in case
of a single cyst < 2.5 cm.
J – Cyst wall: 3 bits inclusive of solid
areas (if larger cysts > 2.5 cm).
Ovarian tumors
• Capsule—intact or broken through.
• Surface—nodular or smooth, consistency firm or cystic.
• Section across the greatest dimension.
• Subsequent sections: pass parallel at 0.5-1 cm in thickness
• Cut surface:
Solid or cystic, papillary or otherwise, cysts—uni or multiloculated
Nature of contents, hemorrhage, necrosis, calcification
Invasion of the capsule.
• 3 to 4 bits if the tumor < 5 cm.
• If >5 cm, one block/1 cm of the tumor
taken across its greatest dimension.
Non neoplastic lesions
• Follicular cyst
• Corpus Luteum cyst
• Polycystic ovarian syndrome
• Ovarian stromal hyperplasia
• Pregnancy Luteoma
• Ovarian endometriosis
• Inclusion cyst
• Ovotestis
FOLLICULAR CYST
Corpus Luteum Cyst
D/D
•Pregnancy luteoma
Leydig cell tumor
POLYCYSTIC OVARIAN SYNDROME
D/D
• Pregnancy
• Stromal Hyperthecosis
Stromal hyperplasia and hyperthecosis
D/D
• Luteinized Thecoma
• Fibroma
Ovarian Inclusion Cysts.
D/D:
serous cystadenoma.
Pregnancy luteoma
D/D
• Luteinized Thecoma
ENDOMETRIOSIS
D/D
• Endometrioid Cystadenoma
• Hemorrhagic Corpus Luteum Cyst
Ovotestis in True Hermaphroditism
WHO Classification-2020
Recent Changes
• Rare entities introduced-mesonephric-like carcinoma & mixed
carcinoma.
• Most important novelty- integration of modern diagnostic criteria with
immuno-molecular algorithms.
• Seromucinous carcinoma is now considered a subtype of endometrioid
carcinoma for its analogous molecular features
APPROACH
Association
Primary tumor Associated tumors
Low grade serous carcinoma Serous borderline tumor
Mucinous Cystadenoma Dermoid cyst, Brenner ctumor, clear cell carcinoma, Large cell neuroendocrine carcinoma,
endometrial carcinoma, Sex cord stromal tumor
Borderline Mucinous tumor Dermoid cyst, Brenner tumor, Intraepithelial carcinoma, Mature cystic teratoma,
Pseudomyxoma peritonei
Malignant Mucinous tumor Mature teratoma, Dedifferentiated carcinoma, Neuroendocrine carcinoma, Yolk sac tumor
Benign Brenner tumor Mucinous neoplasm
Malignant Brenner tumor Mucinous adenocarcinoma
Fibroma Gorlin syndrome, Meig syndrome
Sclerosing stromal Tumor Meig syndrome
Sertoli cell Tumor Peutz Jeghers syndrome
Dysgerminoma Gonal dysgenesis, Gonadoblastoma
Struma Ovarii Dermoid cyst, Papillary thyroid CA, Follicular CA
Primary Tumor Associated tumors
Carcinoid tumor Carcinoid syndrome, MEN 1
Adult Granulosa
cell tumor
Endometrial hyperplasia, Endometrial carcinoma
Juvenile Granulosa
cell tumor
Tuberous sclerosis
Mature cystic
teratoma
Gliomatous peritonei
Mixed germ cell
tumor
Gonadoblastoma
Gonadoblastoma Denys drash syndrome, Frasier syndrome, Turner syndrome, Androgen Insensitivity
syndrome
Solid components
Heterogenous
Origin of ovarian Tumors
SURFACE-EPITHELIAL STROMAL TUMORS
Benign serous tumors
D/D
• Epithelial Inclusion Cyst
• Follicle Cyst
• Struma Ovarii
Serous borderline tumor
D/D
Retiform Sertoli-Leydig Cell Tumor
Low grade serous carcinoma
High grade serous carcinoma
• CA125 >35 U/ml
Mucinous cystadenoma
D/D
• Serous Cystadenoma
• Mucinous Carcinoid Tumor
• Heterologous SLCT
Borderline mucinous tumor (APST)
D/D
• Heterologous SLCT
Mucinous carcinoma
D/D
• Serous and Endometrioid Adenocarcinomas
• Heterologous SLCT
Serous Vs Mucinous Neoplasm
Endometrioid carcinoma of ovary
D/D
• Poorly Differentiated Serous Carcinoma
• Mucinous Carcinoma
Clear Cell Carcinoma
D/D
Dysgerminoma
Yolk Sac Tumor
TRANSITIONAL CELL TUMORS
(BRENNER TUMORS)
D/D
• Serous cystadenoma
IHC
-Immunoreactive for keratin, EMA, and CEA ;
SEX CORD STROMAL TUMORS
FIBROMA
D/D
Thecoma
THECOMA
D/D
Steroid Cell Tumor
Fibroma
ADULT GRANULOSA CELL TUMOR
D/D
Carcinoid Tumor
Endometrial Stromal Sarcoma
SCLEROSING STROMAL TUMOR
Sertoli cell tumor
Differential Diagnosis
Sertoli-leydig Cell Tumor • Carcinoid Tumor
LEYDIG CELL TUMOR
Differential Diagnosis
SLCT
Gyandroblastoma
D/D
Granulosa Cell Tumor
Sertoli Tumor or Sertoli-Leydig Tumor
GERM CELL TUMORS
Mature cystic teratoma (dermoid cyst)
Differential Diagnosis
Immature Teratoma
IMMATURE TERATOMA
D/D
Mature Solid Teratoma • Malignant Mixed Mullerian Tumor
Dysgerminoma
D/D
Solid Yolk Sac Tumor
Embryonal Carcinoma
Yolk sac tumor (Endodermal sinus tumor)
D/D
Clear cell carcinoma
Dysgerminona
Embryonal carcinoma
D/D
Dysgerminoma
YST
Primary ovarian choriocarcinoma
D/D
Dysgerminoma
Embryonal Carcinoma
Struma ovarii
Differential Diagnosis
Mucinous Cystic Tumor
Serous Cystadenoma
CARCINOID TUMOR
Differential Diagnosis
Granulosa Cell Tumor
Malignant mixed germ cell tumor
D/D
Gynandroblastoma
Gonadoblastoma
Gonadoblastoma
Differential Diagnosis
Dysgerminoma
Metastatic tumor
Primary Vs Metastatic
Summary
• Ovary is site of a heterogeneous group of neoplasms as different cell
types present in situ and its relationship with the distal fallopian tube.
• While the majority of ovarian neoplasms are benign or borderline,
malignant varieties represent a significant public health threat.
• Broad range of pathologic conditions are encountered in the ovary in
routine surgical pathology
• Recent significant advances led to an emphasis on accurate histotype
diagnosis by surgical pathologists.
• 1. Cree IA.WHO Blue books, 2020; 5: 32-173.
• 2. GATTUSO P, REDDY VB, DAVID O. Differential Diagnosis in Surgical
Pathology. 2015; 3: 637-675.
• 3. Rosai J, Ackerman. Surgical pathology. 2018;11:1367-1415.
• 4. Robbins, Catron. Patholgical basis of disease. 2020;10 :976-1010.
• 5. Leo et al. What Is New on Ovarian Carcinoma: Integrated Morphologic and
Molecular Analysis Following the New 2020 World Health Organization
Classification of Female Genital Tumors, Diagnostics. 2021; 11(697):1-16.
• 6. Taylor EC, Irshaid L, Mathur M, Multimodality Imaging Approach to
Ovarian Neoplasms with Pathologic Correlation. Radiographics. 2021; 41(1):
289-315.
Reference
THANK YOU

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Ovary.pptx

Editor's Notes

  1. to illustrate origin of ovarian tumours.
  2. Oophorectomy, Salpingo-Oophorectomy, Subtotal Oophorectomy or Removal of Tumor in Fragments, Hysterectomy With SalpingoOophorectomy
  3. Comment on the normal ovarian tissue if present.
  4. Cystic follicles: < 2.5 cm and Follicular cysts when exceeding this diameter; Size- <10 cm in diameter Granulosa cells • Small and round with scanty cytoplasm • Hyperchromatic nuclei with occasional grooves Theca interna cells Larger with abundant cytoplasm and mixed with vessels
  5. leutenised granulosa cells. size>3 cm in diameter
  6. Gross • B/L ovaries; 2-5 x normal size • Mx small, superficial cysts Histopathology • Cortex: thickened, hypocellular & collagenous • Corpora lutea are usually absent
  7. Gross • Nodular hyperthecosis- Mx yellow nodules Histopathology • Luteinization of stromal cells not attached to the follicles. Arranged- singly & clusters oval or round with eosinophilic or vacuolated cytoplasm and round plump nuclei
  8. Gross Small and Mx size < 1cm Invaginations of the surface epithelium Microscopically Lined by a flattened, cuboidal, or columnar epithelium. Psammoma bodies may be seen
  9. Mx in 1/2 of cases, and B/L in 1/3rdv Gross • Small to large nodules: 1.5 - >20cm • C/S: Mx nodular, brown with areas of hemorhage Histopathology • Proliferations of uniform polygonal cells Cytoplasm-abundant eosinophilic, granular • Nuclei- Hyperchromatic, round & large.
  10. Involve B/L ovaries. Size< 10cm in diameter Appearance varies with hormonal fluctuations of menstrual cycle • Postmenopausal women show atrophic glands ;Extensive fibrosis Gross • Red, or dark-brown nodules or cysts • Cyst lining: ragged Histopathology • Epithelium and stroma of endometrium • Hemosiderin-laden macrophages are present
  11. Gross Containing both ova and immature seminiferous tubules or combinations of ovary and testis Microscopy Appearance of the two components.
  12. immuno-molecular algorithms for a better definition and highly diagnostic reproducibility of the different main histotypes .
  13. to illustrate origin of ovarian tumours.
  14. Gross Pathology • Size>1cm Cystadenofibroma-variable solid area Adenofibroma- solid with small cysts Histopathology • Lining-Non stratified cuboidal or columnar • Stroma: dense and fibrous to distinctly edematous
  15. Gross Similar to benign tumors • Cysts lining: fine & firm papillary projections Histopathology • Complex, branching, small papillary projections Papillae lining: Stratified epithelium • Psammoma bodies may be presentMicropapillary-> 5mm area; 5 times longer than wider. Forming medusa head formation.
  16. Invasive serous carcinoma with low malignant potential. Gross Tumor is gritty with large cystic areas with multicystic nodules. Microscopy Inverted macropapillae, unlined clear space Mitosis-3-5/HPF, Central nucleolus rare necrosis<3 fold in nuclear size
  17. Median-60 yr Gross Fallopian tube embedded within tumor Extensive necrosis Microscopy Papillary architecture Large nuclei with high mitosis Necrosis & multinucleated cells >12/10 HPF, nuclear size>3 fold
  18. APST-atypical proliferative serous tumor MPSC- Micropapillary SEROUS CA
  19. Size-few cm to 30 cmGross • Large, mucin-filled, Mx loculated with smooth lining • Stromal component: firm and fibrous Histopathology • Cysts, papillary structures, with no complexity Lining: Simple non stratified mucinous epithelium Fibrocollagenous walls and stroma
  20. Most show mixed mucinous differentiation Gross • Size: 15-20cm in diameter • Cyst lining: bulging masses and papillary projections Histopathology • Filiform papillae, stratification >=10%. Lack destructive stromal invasion Low grade nuclear atypia
  21. Gross Cystic spaces with papillae mixed with solid masses; Hemorrhage and necrosis. Histopathology Mucinous tumor with cytological atypia Infiltrative invasion> 5mm in linear extent
  22. Size up to 20cm. Gross • obvious foci of endometriosis • Predominantly solid & may contain papillae. Histopathology • Endometrioid tumors mimic endometrium epithelium Tumor with destructive invasion with atypia endometrium, containing cells with basophilic cytoplasm, elongated nuclei, and obvious nucleoli. Desirable: Squamous differenetiatn, endometriosis, endometroid adenofibroma component
  23. Average size 15cm in diameter, often surface adhesions Gross • Tumors are cystic with solid areas • Thick-walled unilocular Histopathology Combination of patten with stromal invasion • Hobnail cells have plump hyperchromatic nuclei , low mitotic count
  24. Age of presentation -50 years. Grossly- Tumors vary greatly in size; usually unilateral. Circumscribed rubbery Microscopy Solid and cystic nests of epithelial cells resembling transitional epithelium with fibrous stroma They closely resemble fibromas or thecomas, except for the frequent presence of small cystic areas filled with opaque, viscous, yellowish-brown fluid Borderline- Cystic formations : prominent and with mucinous change. Architectural complexity- crowding, stratification of the epithelium Nuclear atypia but no evidence of invasion. Malignant-rare; Always associated with benign /borderline component
  25. Nonfunctioning tumor with peak incidence: 4th decade GROSS • Cut section: Hard, chalky white. Areas of edema, hemorrhagic & calcifications MICROSCOPY Intersecting bundles of spindle cells, in a storiform pattern • Diffuse intercellular edema IHC- • Inhibin: focally positive • Vimentin: positive D/D-Massive Edema and Fibromatosis
  26. Incidence: Postmenopausal women; peak -6th decade Gross Pathology •Unilateral up to 10cm. • Lobulated, solid, sometimes with cystic change, hemorrhage, and necrosis • Foci of calcification may be seen Histopathology • Diffuse growth of tumor cells in syncytial • Stroma- hyaline plaques and focal calcification Pale grey cytoplasm; Foci of calcification may be seen Positive for inhibin, calreticulin
  27. Postmenopausal, peak incidence in the 5th decade Gross Pathology • Usually unilateral Nodular; Size- 10cm • Solid with cystic areas and hemorrhage Histopathology Granulosa cells with typical nuclear features • Groups of granulosa cells form Call-Exner bodies Call-Exner bodies: small, round cystic spaces containing eosinophilic material or pyknotic nuclei Pattern-Trabecular pattern • Insular pattern • Macrofollicular pattern • Water silk pattern • Gyriform pattern • Diffuse and sarcomatoid
  28. Rare & benign, Incidence- 1st 3 decades, with a peak in 2nd decade Gross Pathology • Unilateral, solid, Well circumscribed tumor • Foci of edema, cyst formation Histopathology • Pseudolobules with epitheloid & spindled cells. Hypocellular edema with collagenous stroma Special Stains and Immunohistochemistry • Positive for Inhibin, CD34 & CD31 Sclerosis is present within the nodules Thin dilated vesssels –hemiangiopericytoma like appearance.
  29. Incidence: childbearing age; peak- 2nd decade Gross Pathology • Solid, lobulated tumor; size 9cm • Cut surface- Variegated, yellow or brown Histopathology • Tumor: round or elongated hollow or solid tubules • Stroma may be hyalinized and focally replace the tubules Sertoliform tubules with low cuboidal cells with bland nuclei.; positive for sex cord stromal markers Hollow tubules: lined by cuboidal, columnar cells with moderate to abundant pale, eosinophilic cytoplasm • Solid tubules: closely packed with small nuclei and scanty cytoplasm or large cells with abundant cytoplasmic lipid. Special Stains and Immunohistochemistry • Cytokeratin and inhibin positive • EMA negative • Calretinin, focal Differential Diagnosis Sertoli-leydig Cell Tumor • Carcinoid Tumor MALIGNANT; Size> 5cm, mitosis> 5/10 HPF
  30. Rare, benign steroid cell (hilus cell tumor); Located near the hilum, Incidence: 5th decade Gross Pathology • Circumscribed, solid, reddish lobulated Histopathology Polyhedral cell with eosinophilic cytoplasm Ctyoplasmic reink’s crystal Special Stains and Immunohistochemistry • Inhibin positive • Electron microscopy: rod-shaped crystals of Reinke
  31. Benign tumor with elements of both amle and female differentiation. Gross- solid, cystic with pale white areas Histo- combination of granulosa cell and sertoli cells
  32. Often asymptomatic, May present with pain, swelling, or uterine bleeding Clinical Features • Most commonly during the reproductive years Gross Pathology • Combination solid and cystic mass Histopathology • Mature tissues with atleast 2 germ layers Neuroectodermal elements: glial, PNS, cerebrum & cerebellum • Mesodermal elements: smooth muscle, bone, teeth, cartilage, and fat • Endodermal elements: respiratory & gastrointestinal epithelium, thyroid tissue
  33. Rare, rapidly growing, malignant tumor. Incidence: 1st and 2nd decades Gross Pathology • Unilateral tumor with large fleshy • Cut surface: Solid,cystic areas with hemorrhage and necrosis Histopathology Mostly neuroectodermal tubules & rosette admixed with other 2 germ layers Differential Diagnosis
  34. Often >1 kg) Most patients are young Gross: Typically 15 cm flesh, yellow & lobulated. Foci of hemorrhage and necrosis Microscopically: Tumor cells in well-defined nests separated by fibrous strands infiltrated by lymphocytes . Calcificatn- gonadoblastoma Consistently reactive for PLAP and CD117
  35. Elevated AFP: monitor the effectiveness of therapy Incidence: 2nd -3rd decade Gross Pathology • Unilateral, Typically 15cm in diameter Solid & cystic areas with hemorrhage and necrosis Histopathology Schiller-Duval bodies are characteristic. • Epithelial-lined space with polypoid projection & central vessel Other structural variants include polyvesicular, hepatoid, glandular, papillary, myxomatous, macrocystic, and solid Special Stains and Immunohistochemistry • AFP +ve cytoplasmic stain: focal or diffuse • Creatine kinase +ve cytoplasmic stain
  36. Signs and symptoms related to an adnexal mass and sometimes associated with endocrine manifestations, including isosexual precocious puberty and irregular bleeding Rare tumor affecting children and young adults; Gross Pathology • Unilateral solid hemorrhagic & necrotic mass Histopathology Tumor cell: glandular, papillary & solid pattern. Frequent mitoses with foci of necrosis and hemorrhage HCG elevated; used as a tumor marker
  37. S. HCG –elevated; precocious puberty in children Rare; occurs in children and young adults Gross Pathology • Unilateral solid, gray-white hemorrhagic with necrosis • Depends on other germ cell components Histopathology • Mixture of cytotrophoblast and syncytiotrophoblast. Cytotrophoblastic : centrally within the tumor surrounded by syncytiotrophoblastic cells. Syncytiotrophoblastic: large and basophilic with vacuolated cytoplasm and many hyperchromatic nuclei Mononucleate cytotrophoblasts: clear cytoplasm and obvious cell borders; small, centrally located, round, hyperchromatic vesicular nuclei
  38. Occurs most in reproductive years ; Associated with thyroid enlargement Gross Pathology • Unilateral, < 10cm in diameter • Fluid-filled cysts with Hemorrhage, necrosis & fibrosis Histopathology • Thyroid tissue or adenoma with areas of follicles • Follicles with colloid mixed with solid, cellular areas Special Stains and Immunohistochemistry • PAS-colloid • Thyroglobulin Solid, brown or green-brown, separated by fibrous septa, with or without an associated mature cystic teratoma.
  39. 30-80 yrs; Elevated urinary 5-hydroxyindole acetic acid Gross Pathology • Unilateral solid ,cystic -small nodules Histopathology • Insular carcinoid: Groups of small uniform cells separated by stroma • Nucleus: Salt & pepper chromatin Carcinoid syndrome consists of flushing, diarrhea, abdominal cramping, and, often, cardiac involvement Positivity for NEC MARKERS
  40. Mixed germ tumor with Yolk sac tumour, embryonal ca & immature teratoma Gross Pathology • Solid & cystic area with Hemorrhagic & necrotic areas Histopathology •2 or more germ cell components. Yolk sac tumor /Embryonal ca with >3 mm
  41. Affect children and young adults • Phenotypic women with underlying gonadal disorder Gross Pathology • Solid, lobulated, and speckled with calcifications • Gonad: inguinal testis or a gonadal streak Histopathology Mx variable sized cell nests with fibrous stroma 3 components: germ cell, sex cord, globular BM Histo-calcificatn
  42. Bilateral tumour metastatic to the ovaries Grossly Rounded or kidney shaped large masses in B/L ovaries. C/S: Grey-white to yellow fleshy tumour. Microscopically Mucus-filled signet ring cells- singly or in clusters. Sarcoma-like cellular proliferation of ovarian stroma The Krukenberg tumour is generally secondary to a gastric carcinoma, but other primary sites where mucinous carcinomas occur (e.g. colon, appendix and breast GROSS-Areas of haemorrhage and necrosis.
  43. Ovarian carcinoma is the second most common gynecologic malignancy and the 5th leading cause of cancer death in females