Histology

Question 1

Ovarian lesion removed from 42 yo women.

1. Describe the histology features (1pt) What is the diagnosis?
2. What tumour marker would you expect would have been elevated pre-operatively?
3. What further treatment/surgery (if any) would you recommend?

Answer 1

1. Benign glandular epithelium with cuboidal to columnar cells with focal ciliated cells.
   
   1. Serous Cystadenoma
2. Nil
   
   1. Nil - benign

Question 2

58 women with an adnexal mass

1. Describe the histology features (1pt)
   
   1. What is the diagnosis?
2. What tumour marker would you expect would have been elevated pre-operatively
3. What further treatment/surgery (if any) would you recommend?

Answer 2

1. Marked nuclear and cellular pleomorphism with prominent nucleoi. Sheets of cells with slit like spaces. Psammoma bodies present.
   
   1. High grade serous carcinoma
2. CA 125
3. Clinical assessment - consideration of upfront surgery vs Neoadjuvant chemotherapy.

Question 3

1. Describe the histology features (1pt)
2. What is the diagnosis?
3. What tumour marker would you expect would have been elevated pre-operatively
4. What further treatment/surgery (if any) would you recommend?

Answer 3

1. stratified / pseudostratified epitherlium with branching papillae (hierarchical branching). MIld to modern atypia with few mitosis. Some nuclear and cellular pleomorphism with cytoplasmic clearing in places
2. Serous borderline tumour
3. May have none or may have and elevated CA125
4. Clinical assessment. Needs surgical staging. Need to identify whether there is microinvasion which is more commonly associated with micropapillary variant which this is not.

Question 4

23 yo women with a 6cm solid and cystic lesion.

1. Describe the histology features (1pt)
2. What is the diagnosis?
3. What tumour marker would you expect would have been elevated pre-operatively?
4. What further treatment/surgery (if any) would you recommend?

Answer 4

1. Ciliated columnar epithelium lining the cyst. Glandular tissue deeper with pink coloured secretion - resembling thryoid tissue
2. Mature teratoma with thyroid tissue - if > 30 % thyroid tissue would be a struma ovarii
3. None in a benign mature teratoma
4. No further action needed in a mature teratoma there is a ~10% chance of bilateral tumour and a < 5% chance for recurrence.

Question 5

55 y.o. women with a solid vascular tumour

1. Describe the histology features (1pt)
2. What is the diagnosis?
3. What tumour marker would you expect would have been elevated pre-operatively?
4. What further treatment/surgery (if any) would you recommend?

Answer 5

1. microfollicular phenotype with small cells with marked nuclear pleomorphosism and prominent nucleoi. Numerous Call-Exner bodies ( giving a follicle-like appearance, are small eosinophilic fluid-filled punched out spaces between granulosa cells. The granulosa cells are usually arranged haphazardly around the space. They are pathognomonic for granulosa cell tumors)
2. Adult Granulosa cell tumour
3. May have elevated AMH, Inhibin B. May present with symptoms of hyperestrogenemia
4. Needs clinical assessment +/- surgical staging. May be suitable for upfront surgery. Stages IC2 and above recommended for 3 cycles of BEP or 6 Carbo/Taxol

Question 6

63 yo women with bilateral 8 cm cystic ovarian neoplasms

1. Describe the histology features (1pt)
2. What is the diagnosis?
3. What tumour marker would you expect would have been elevated pre-operatively?
4. What further treatment/surgery (if any) would you recommend?

Answer 6

1. mucinous epithelial cells originating from appendiceal lumen with abundant apical mucin and elongated nuclei. Scalloping of glands
2. Mucinous tumour ddx primary ovarian, Appendix and GIT, pancreas and breast Mets ( int his case appendix)
3. CEA and CA 19-9
4. If not done previously imaging with CT C/A/P undertaken with breast examination. May need complete surgical staging if not done. IHC may be helpful.

Question 7

28 yo women with bilateral ovarian lesion - cystectomy with intact specimen.

1. Describe the histological features?:
2. What is the diagnosis:
3. What IHC would you expect to be positive:
4. Associated genetic mutations?

Answer 7

1. Describe the histological features?:
   
   1. There is stratified/pseudostratified epithelium with nigher N: C. the nuclei are bland. At the top of picture, there are some areas of micropapillae. the arrows are pointing to areas of microinvasion in the stroma
2. What is the diagnosis:
   
   1. SBOT - micropapillary variant with microinvasion
3. What IHC would you expect to be positive:
   
   1. Positive for CK7, ER, PR, CD15, MOC21, BerEP2 CAM5.2
   2. Negative for CK20, CEA, HER2, Calretinen
4. Associated genetic mutations?
   
   1. Serous borderline and low-grade invasive tumors express BRAF, KRAS, and occasional PIK3CA mutations

Question 8

20 yo women with an elevated “germ cell” tumour marker a large adnexal mass removed.
1. What are these structures called?
2. Which tumour marker would be elevated
3. What tumour is it from
4. What is the standard first line chemotherapy for this tumour.

Answer 8

1. Schiller-Duval Body - present in ~50%. Pathognominic. Vessel surrounded by fibrous core wiht surounding tumour cells.
2. AFP
3. Yolk Sac / Endodermal sinus tumou
4. BEP for 3 -4 cycles (ESMO guideline Non-Epithelial Ov Ca)

Question 9

Histo of RPOC. Describe the histology. What is the DDx and what IHC is crucial. a

Answer 9

There are enlarged irregularly shaped villi. Which are hydropic.
This could be a hydropic MC DDx Partial molar pregnancy. p57 will differentiate between partial and complete mole.
Difference between partial mole requires molecular testing to identify diandric tripoidy (>95%0.

Question 10

These are curettings from a suspected molar pregnancy. Describe histopath and IHC and follow up + indications for treatment.

Answer 10

There are large hydropic villi. Cystic spaces (aka cistern). There is cirumferential trophoblastic proliferation. There are no foetal vessels or RBCs.
These would be p57 -ve as there is no maternal DNA. they would be Androgenic diploid.
Follow up in specialised centre with weekly hCG.
Indicators for treatment - increase in 10% over three readings. no drop <10% over four readings.
FIGO indications for Rx include above and persistence more than 6 months after evacuation.
CXH - hCG more than 20000 four weeks post evacuation - RANZCOG as well.

Question 11

Complete mole. Rising hCG at 2 months. negative metastatic screen. family complete. Simple hysterectomy. Pathology below.
Describe
Diagnosis
Treatment

Answer 11

There is a large dilated villi. It is invading into the myometrium as there is direct contact with the smooth mucle and no intervening decidua. DDx: invasive mole. Chorio carcinoma should have no villi.
Clnical review, Hx and review imaging. MDT review.
Post hysterectomy with no residual disease. monitor hCG as per post treatment criteria. RANZCOG indicates Monthly βhCG for 12 months, advise not to conceive during that time. CXH follow up with urine hCG for life. 4 weekly hCG yr 2, 8 weekly yr 3, 3/12 year four and on.
Treat as per WHO score if recurs.

Question 12

A 35yo women presents with widespread metastatic disease 6 months post partum. She is admitted under med onc and a liver biopsy is undertaken. After the biopsy she develops a large haematoma. TIssue histo is below.
Describe histo & what IHC
What factors make up the WHO Score
WHO score is 13 - plan?

Answer 12

There are solid aggregates of mononuclear and multinucleated trophoblasts are found within fibrin deposits. There is signficant nuclear and cellular pleomorphism. There are no villi formation. The DDx in the case of is broad. IHC in CHoriocarcinoma would be +ve for hCG, hPL, inhibin, MUC4, p63. THe Ki67 index is likley to be very high (>90%) and the serum hCG as well.
WHO score consists of HAM CLANS
HCG
Age
Months from previous preg
Chemo tried before
Largest tumour in cm
Antecedent pregnancy
Number of mets
Size of mets

WHO Score of >12 is ultra high risk disease. THis is rare and dangerous. I would consider expert opinion on management. Standard includes EP EMA. This is normally undertaken with induction EP
Etoposide 100mg/m2/day IV and
cisplatin 20 mg/m2/day IV
on Days 1 and 2 every 7 days for 1–3 courses prior
to starting EMA/EP or EP/EMA

Question 13

Vulva biopsy. Describe histopath. DDx. What IHC is useful.

Answer 13

This is a vulval biopsy with full thickness atypia. The rete ridges are wide and deep. There is no clear invasion. The DDx is VIN either usual or dVIN. Melanoma and paget’s also DDx. No pagetoid cells.
IHC -
p53 mutation common in dVIN. p16-ve and GATA3 -ve
p16 abnormal in VIN.
Paget’s PAS
Melanoma S100, MelanA, HMB

Question 14

Vulval biopsy.
Desribe pathology
IHC useful
Treatment

Answer 14

This is a vulval biopsy with maturation of the cells through the epidermis. There are multiple atypical cells throughout the epidermis. The cells are large with pale cytoplasm. the nuclei have prominant nuclosu.
They are CK7 +ve unlike HSIL. PAS +ve. GATA3 +ve - UNLIKE dVIN.

Question 15

Cystectomy in 21 yo with torted ovary.
Describe path.
What IHC would help.
DDx

Answer 15

There are nests of monotonous tumour cells are separated by thin fibrous septa containing lymphocytes. The nuclei have prominant nucleoli. The cells have well defined cell borders with clear cytoplasm. Nuclei are often squared off.
IHC: combination of SALL4, OCT 3/4 +ve and SOX2 -ve - useful in combination for other germ cell tumours.
DDx Other germ cell tumours. juvenile granulosa cell tumour (SF1, inhibin, calretinin, WT1 +ve) Sertoli-Lleydig tumour - poorly differentiate. Metastatic from another site.

Question 16

32 yo cystectomy by general GYN.
Desribe Histo
IHC
Dx and DDx
Grade?

Answer 16

This is an ovarian lesion with small glands. It is a dual population of cells with atypical cells between the glands. There columar cells ahve retained polairty with mild nuclear typia. This would be consistent with a well differentiated sertoli-leydig cell tumour as the glands are well developed as the differentiateion is based on teh degree of tubular dfferntiation of hte sertoli cell compoenc and teh amount of primitive stroma whih increases.
TO differentiate from Germ cell - SALL4, OCT 3/4 adn SOX2.
Sertolic cells typically +ve for inhibin, SF1, WT1, Carlretinin and FOLXL2.
Associated with DICER1 syndrome (also with papillary thryoid Ca)

Question 17

A 42 yo women presents with AUB. CST was NAD. On examination cervix appears abnormal. Cx biopsy is below.
Describe
IHC
DDx
Associated with mutation/ syndrom/ other Gyn Ca.

Answer 17

The tumour forms glands with mucin. The cytoplasm is granular. The cells ahve distinct borders. The nuclei uniform in size with abnormla nuclei. There may be a mitotic body int he upper right corner and on the left.
This is consistent with a glandular malignancy of the cervix. I woul dperform IHC with p16, ER, PR, PAX8, CEA, CK20 and CDX2. P53

Suspect HPV independent gastric type adenocarcinoma. THis would be ER , PR -ve. p16 -ve or focally +ve. PAX8, CK7 and CEA +ve. p53 abnormal in ~ 50% of cases.
Previously known as adenoma malignanum. they can be seen in Peutz Jegher syndrom which is assocaited with a germline mutation in STK11. Other gyn Cancers include Sex cord tumour with annular tubules. SCTAT

Question 18

A 56 yo presents with pain and a pelvic mass is identified. The CA125 is 42. All others Normal. She undergoes a TAHBSO + Staging. All biopsies -ve, washings +ve. Nodes not done.
Describe histo and IHC
Stage
Recommendations for Mx.

Answer 18

This is a high power image of the ovary. There are sheets of abnormal cells. They ahve clear cytoplasm and rounded nuclei with centrally placed nucleoi which are eccentrally place. Hyaline bodies are present. (hyaline - cartilagenous areas - pink bodies). No clar hobnail nuclei. suspect clear cell carcinoma or clear cell type of another.
IHC - ER / PR, WT1 -ve PAX8, AMACR, NAPSIN, HNF1B, +ve
WIthout nodal staging this is an incompletely stage stage IC3 CCC of the ovary.
Options for Mx include:
Systemic treatment iwth carboplatinum and paclitaxel. This is recommended by both ESGO and NCCN.
Observation given the relative chemoresistance of CCC
Evidence from retrospective studies primarily from Canada that adjuvant radiotherpay will help with recurrence.