8132MED - Pathology-Diseases of FGT 160924.pdf

Repro Pathology- 2 09/2024 Female Genital Diseases Associate Professor Vinod Gopalan...

Repro Pathology- 2 09/2024 Female Genital Diseases Associate Professor Vinod Gopalan Medical Education & Histopathology School of Medicine & Dentistry Pre-reading required- Repro Clinical Histology and Pathology Vinod Gopalan, Pathology, School of Medicine, Griffith University  COMMON CLINICAL PRESENTATIONS discharge - external or internal genitalia problem Vinod Gopalan, Pathology, School of Medicine, Griffith University  (A, Courtesy of Dr. Alex Pathology- Female Genital Diseases Ferenczy, McGill University, Montreal, Quebec, Canada.) EXTERNAL GENITALIA multiple lesion VULVA: Inflammatory diseases are common (Eg- Vulvitis). Non neoplastic diseases include condylomas, Lichen sclerosis and lichen simplex chronicus. HPV multiple strains transcervix to vulva Malignancies are rare (~3%). HPV related (16 &18)- with precancerous lesions -Vulvar intra 6, 11 - low risk LIKLEY DIAGNOSIS? condyloma - HPV 6 & 11 epithelial neoplasms (VIN) genital warts Aetiology ? February 2017 Clinical Case Reports 5(4) VAGINA: Inflammatory diseases with leukorrhea (Eg- Vaginitis). Commonly associated with candida albicans and Trichomonas vaginalis. Malignancies are uncommon (SCC, Clear cell Adenocarcinomas and Sarcoma) can be severe fibroid sppearance condyloma lata and condyloma accuminata Vinod Gopalan, Pathology, School of Medicine, Griffith University Lichen sclerosis vs Lichen simplex thickened skin, licenification of skin less epidermis and some collagen keratin and thinner lichen sclerosis higher risk of malignancy Lichen simplex- Diagnosis ▪ Itch ▪ Erythematous scaling plaques with irregular borders. ▪ Thickened vulvar skin ▪ Lichenification ▪ Biopsy- Acanthosis increased thickening of some bleeding spots leathery skin, bark-like squamous epithelium on removal of plaque ▪ Treatment ? Topical steroids not erythematous unless itch https://www.roshreview.com/practice-questions/creog Lichen sclerosis- Diagnosis Itch and soreness more collagen and much thinning epidermis elevated risk White papules/plaques with echymosis Dyspareunia and dysuria Biopsy- Inflammation and thinning of epidermis. Increased risk of SCC lichen simplex lichen sclerosis thin epidermis collagen thin keratin more pain - thin epidermis Vinod Gopalan, Pathology, School of Medicine, Griffith University Identify the pathologies Paget’s Disease- Vulva Medicina 2021, 57(10), 1029; https://doi.org/10.3390/medicina57101029 Extramammary Paget’s disease is a rare condition, affecting 6.5% of all patients with Paget’s disease. The most common extramammary site is the vulvar area. most common Paget’s disease is characterized by Intraepithelial neoplasia. almost always carcinoma not malignancy Only a minority of cases of vulvar (extramammary) Paget disease have an underlying tumor (opposite to breast). The neoplastic cells arise from the epidermal progenitor cells. Clinical features and presentation Mean age= 72+ 4 of older age Pruritis+. inflammation much higher Vulvar lesions are often erythematous and appear white deposit as a red skin covered with white coating diagnose w/ biopsy (referred as cupcake frosting appearance) well demarcated, white frosting squamous cells appear much larger Mostly pre-invasive lesions. with empty cytoplasm Vinod Gopalan, Pathology, School of Medicine, Griffith University Paget’s Disease- Vulva Medicina 2021, 57(10), 1029; https://doi.org/10.3390/medicina57101029 enlarged white frosty nucleus appearance clear cytoplasm large tumour from high activity of mitochondria irregular boundaries but well demarcated Preoperative images of the Paget’s disease showing the erythematous plaque with Large tumor cells with pale-pink white patches (a) and the extent of the wide local excision (WLE) (b) cytoplasm are seen infiltrating the epidermis. Chronic inflammatory cells are present in the underlying dermis. Vinod Gopalan, Pathology, School of Medicine, Griffith University Paget’s Disease- Vulva Medicina 2021, 57(10), 1029; https://doi.org/10.3390/medicina57101029 Intraoperative images of the first specimen of the WLE (a,b) and the final plastic reconstruction of the skin (c). What is the indication for WLE? All patients baring a biopsy where PD cells are present should be treated with a wide local excision, while other non-surgical treatments can be considered depending on the patient's individual characteristics and histopathology results. Follow up is a must Vinod Gopalan, Pathology, School of Medicine, Griffith University Pathology- Female Genital Diseases INTERNAL GENITALIA some allergic to condoms CERVIX: Cervicitis: Clinically present as purulent vaginal discharge Types: Infectious and non infectious Vulvovaginal candidiasis is caused by Candida albicans https://www.gponline.com/basics-vaginal-discharge/infections-and-infestations/infections- and-infestations/article/1033896 Aetiology -Chlamydia Trachomatis, Trichomonas vaginalis, Neisseria gonorrhoea, HSV-2 & HPV PCR to confirm HSV more ulcerative Diagnosis: Full pelvic exam (colposcopy and pap smear); PCR more prominent Management: Antibiotics Malignancy: - HPV related 6-11 warty lesions heterogenous - unexpected vaginal bleeding, leukorrhea, painful coitus (dyspareunia), or dysuria. painful sexual intercourse - Surgical management confirm by biopsy Vinod Gopalan, Pathology, School of Medicine, Griffith University Volume 13 - 2022 | https://doi.org/10.3389/fphar.2022.911962 Front. Pharmacol., 27 May 2022 CERVIX- Malignancy non-keratinsed in cervix HPV related carcinogenesis starts with a precancerous lesion called squamous intra-epithelial lesion (SIL). cervix - handy for iRAT ectocervix or endocervix in junctional region basal - see mature bottom 1/3 lesion is the start, then atypia CIN-1 and squamous rises from basal cells to mature Normal- zonal difference present Classification Systems for Premalignant Squamous Cervical lesions ectocervix as has squamous epithelium Dysplasia / Cervical Squamous Carcinoma in Situ Intraepithelial Intraepithelial Neoplasia Lesion CIN I-III dysplasia Mild dysplasia CIN I Low-grade SIL in epithelium clinical - diagnosis how atypical they are level of abnormal cells not require Moderate dysplasia CIN II High-grade SIL much LSIL- 60% regress treatment MIDDLE 2/3 HSIL- 20% regress Severe dysplasia CIN III High-grade SIL much higher risk WHOLE AREA Carcinoma in situ CIN III High-grade SIL VINOD GOPALAN, Pathology, School of Medicine, Griffith University CERVIX- Malignancy HPV main cause Pathophysiology HPV, DNA virus, uses host cell DNA polymerases to replicate its genome and produce virions. repair damaged DNA Normal- Host cell DNA replication stops as the squamous cell maturation completed and this also prevent the virus production. to lesions trigger damage HPV infection- HPV “solves” this problem through the action of two viral oncoproteins, E6 and E7. The E6 and E7 proteins of “high risk” HPV variants inhibit p53 and RB, respectively, two tumor suppressors that act to suppress the division of squamous cells as they mature. Important TSGs HPV- related cervical malignancy (CIN & invasive Ca) Risk Factors Low risk HPV (6, 11)- Condyloma warty 1.Early age at first intercourse High risk HPV (16, 18)-CIN and Carcinoma 2.Multiple sexual partners CIN from the high risk types 3.Male partner with multiple previous sexual partners 4.Persistent infection by high-risk strains of papillomavirus Vinod Gopalan, Pathology, School of Medicine, Griffith University Cervical Cancers What is the most significant cellular pathology in both cytology and biopsy high N:C ratio here ? Reduction in the cytoplasm nucleus pleomorphic and the increase in the nuclear-to-cytoplasm ration as the grade of the lesion increases Papanicolaou smear- (A) Normal cells (B) Low-grade squamous intraepithelial lesion (LSIL). (C and D) pap smears not done extensively anymore Both high-grade squamous intraepithelial lesions (HSILs).This observation reflects the progressive loss PCR test done of cellular differentiation on the surface of the cervical lesions from which these cells are exfoliated. colour - indicate maturity; red to pink = mature; blue-green - immature cells how atypical squamous cells look like high grade in these 2 Spectrum of squamous intraepithelial lesions (SIL) with normal squamous epithelium for comparison: LSIL with koilocytotic atypia; HSIL with progressive atypia in all layers of the epithelium; and HSIL with diffuse atypia and loss Vinod(carcinoma of maturation Gopalan, Pathology, in situ,School of Medicine, far right image). Griffith University CERVIX- Malignancy Diffuse positivity with p16 in the cervix can be regarded as surrogate marker for presence of hifgh risk HPV Diagnosis Dual-stain testing on Pap test samples identifies the presence of two proteins: p16 (brown) and Ki-67 (red). cell proliferation marker HPV cervical infection. Light micrograph of a cervical smear key in the HPV diagnosis identify level of cell activity revealing epithelial cells infected with the human papilloma Ki67, p16 virus (HPV). PAP Test or HPV test HPV test is the DNA test which amplify the viral DNA fragment via PCR*. PAP smear test looks for all cellular changes- atypical, precancer lesions and invasive cervical cancers. identify atypical cells Co-testing can be done Molecular stains- Dual stains is a new approach (refer to image on top right) Vinod Gopalan, Pathology, School of Medicine, Griffith University CERVIX- Malignancy INVASIVE CANCERS Clinical features- Unexpected vaginal bleeding, leukorrhea, painful coitus (dyspareunia), or dysuria. Tumors encircling the cervix and penetrating into the underlying stroma produce a barrel cervix. Identified by direct palpation. Cervical diameter widens >4cm. direct palpation as well Extension into the parametrial soft tissues can affix the uterus to the surrounding pelvic structures. Pelvic LN+ The risk of metastasis: bladder under Tumours 3mm= 10% cervix diation barrel-cervix in cervical cancers cervical cancer heterogenous invasion into parametrium Barrel-shaped thickening and loss of normal low signal intensity of Vinod Gopalan, Pathology, School of Medicine, Griffith University the cervix that invades into the upper anterior and posterior walls of the vagina and parametrium. CERVIX- Malignancy INVASIVE CANCERS looks different and heterogenous hypoechoic, widened cervix Although cervical cancer is staged clinically, ultrasound can be a useful adjunct by showing size (4 cm) parametrial invasion tumor invasion into the vagina tumor invasion into adjacent organs hydronephrosis: implies stage IIIB tumor. US -HIGHER CLINICAL SIGNIFICANCE squamous cell nests Microscopic Pathology: Squamous cell carcinoma of cervix. Ultrasound Pathology: Uterine cervix shows hypoechoic, heterogeneous mass. Cervix is much larger than uterine body. highly immature less keratin What is the arrow indicative of? anechoic fluid in endometrial canal of body red - keratin deposition endometrial fluid trapped in wall Vinod Gopalan, Pathology, School of Medicine, Griffith University CERVIX- Malignancy INVASIVE CANCERS CLINICAL STAGING FIGO staging system- by the International Federation of Gynecology and Obstetrics. In general, there are five stages: FIGO for staging Stage 0: carcinoma in situ in the epithelium Stage I: Localized to the organ of origin outside uterus Stage II: invasion of surrounding organs or tissue surrounding tissues Stage III: spread to distant nodes or tissue within the pelvis lymph nodes or pelvis Stage IV: distant metastasis heterogenous mass irregular haemorrhage Vinod Gopalan, Pathology, School of Medicine, Griffith University https://screening.iarc.fr/atlascolpodetail.php? CERVIX- Malignancy INVASIVE CANCERS Colposcopy Two patient images of genital pathologies are shown here. Which patient (Left or Right?) should have the colposcopy postponed ? Small ulcerating lesion left has discharge Active infection - postponed if severe cervico-vaginal inflammation making satisfactory visualisation of cervix difficult. If inflammation of cervicovaginal region is accompanied by a growth of ulcer on the cervix, a biopsy of the growth or ulcer should be obtained without further delay Vinod Gopalan, Pathology, School of Medicine, Griffith University UTERUS Endometritis- with pelvic inflammatory disease. Abnormal location of endometrial tissue- Adenomyosis & Endometriosis. endometrial tissue in myometrium or perimetrium malignancy bleed Abnormal Uterine bleeding- Menorrhagia, metrorrhagia and post menopausal bleeding. heavy and profuse under irregular bleed bleed b/w Proliferative lesions- Hyperplasia, polyps, benign tumours &carcinoma Endometriosis fallopian tube, ovary, pelvic floor and mesentery fat Presence of endometrial glands and stroma outside the uterus. menstruation These ectopic endometrial tissues are functional* and abnormal. go outside and go into ovary Compared to normal endometrium, these ectopic tissues exhibit or regurgitation increased levels of inflammatory mediators (eg-Prostaglandin E2). Clinical characteristics: dysmenorrhea, menorrhagia, dyspareunia, painful sexual chronic pelvic pain, and menometrorrhagia intercourse heavy bleed b/w periods bleed more and more painful reproductive age - 20-30s most common Proposed pathophysiology of endometriosis. metastasis theory 20-45 other is metaplastic theory - change in tissue type cell replaced due to severe change stem cell theory Vinod Gopalan, Pathology, School of Medicine, Griffith University UTERUS- PATHOLOGY Endometrium Cross section through the wall of a hysterectomy specimen of a 30-year-old woman who reported chronic pelvic pain and abnormal uterine bleeding. Likely pathology? Adenomyosis more endometrial glands Serosa 20% co-exist with endometriosis 50% w/ leiomyomas (uterine fibroids) https://radiopaedia.org/cases/adenomyosis-of-the-uterus-gross-pathology-1 close to serosa layer - bleeding dilated endometrial glands US pathology from a 30-year-old female presented with 2months of heavy PV bleeding is shown here. Describe the pathology? Doppler US Increased myometrial hyperaemia suggest adenomyosis Blue/red marking - high blood flow 2 months of heavy bleeding Vinod Gopalan, Pathology, School of Medicine, Griffith University UTERUS- PATHOLOGY uterus fluid much brighter Insights into Imaging volume 8, pages549–556 (2017) Identify the pathology and the likely presenting Identify the pathology and the likely presenting complaints in this case- complaints in this case- Yellow endometriosis endometrial line No bladder infiltration lumen Infiltrative endo Junctional zone - identify pathologies Red is junctional area gap b/w endometrium and myometrium green - where endometrial red - junctional area Diffuse adenomyosis Sagittal T2-weighted image, thicken junctional zone cannot appreciate with punctate high-intensity myometrial foci (white arrow) Vinod Gopalan, Pathology, School of Medicine, Griffith University  much thicker in adenomyosis junctional zone - b/w endometrium and myometrium - cyclical changes in thickness hyperechoic lines (yellow) separated by hypoechoic endometrium subendometrial line (red) b/w green and red line - disturbed with pathology UTERUS- PATHOLOGY Superficial vs Deep Endometriosis https://radiologyassistant.nl/abdomen/unsorted/endometriosis-mri-detection outside zone less likely to infiltrate NEED LAPAROSCOPY EXAM Superficial serosal implants of endometriosis superficial endometriosis Samspon syndrome: Endometrial plaques are superficial and are scattered on the serosal lining of the peritoneum, ovaries and uterine ligaments. Minor symptoms. Lesions will be tiny and flat (almost undetectable). Radiologically detectable when they are >5mm. more common compared to Cullen's Cullen’s syndrome: Sub-peritoneal infiltration of the endometrial deposits. Severe symptoms. Surgical intervention is needed. severe infiltration infiltration on right, spread into rectum Endometriosis infiltrating the rectum Endometriosis infiltrating the bladder left - no infiltration Vinod Gopalan, Pathology, School of Medicine, Griffith University UTERUS- PATHOLOGY ENDOMETRIAL HYPERPLASIA (Refer practical notes for more information) Proliferation of endometrial glands (>10mm) due to excessive oestrogen stimulation and insufficient progesterone. Precursor lesion for endometrial carcinoma. progestin to oestrogen 1/3 of carcinoma Aetiology/Riskfactors: Unopposed and prolonged Common clinical presentation: Abnormal PV bleeding Estrogen exposure. all induce endometrial hyperplasia Obesity, T2DM, PCOS, Hormone Replacement (HRT), need histology Grading: Two types Pregnancy, Estrogen secreting ovarian tumours etc with to carcinoma 1- With atypia thick and collection of anechoic fluid 2- Without atypia Superficial serosal implants of endometriosis Case courtesy of Maulik S Patel rID: 30100 Ultrasound Pathology Endometriosis infiltrating the rectum Microscopic Pathology Endometriosis infiltrating the bladder increased endometrial thickness (-12 mm) stroma looks hyperaemic endometrual glands undergo multiple cystic spaces noted in endometrium glandular and stromal hyperplasia hypertrophy haemorrahge ENDOMETRIAL HYPERPLASIA April 2014 Gynecologic Oncology Reports 8:21-3 Dilation and curettage endometrial thicken with polypoidal mass Management: Dilation and curettage specimens. Progestin therapy induce endometrial glands to thin push glands into secretory phase A- Polypoid masses (Gross) Hysterectomy if there is atypia* B- Polypoid mass (Micro) shed and thinning C- Endometrial glands and stroma receptors more blunt, less receptor formation D- Immunostaning of αSMA is positive in the stroma smooth muscle actin - confirm involvement of smooth muscle fibres Vinod Gopalan, Pathology, School of Medicine, Griffith University UTERUS- PATHOLOGY ENDOMETRIAL CANCER Cancer - hyperplasia and microsatellite mutations Risk factors 1. HNPCC Lynch syndrome microsattelite mutation 2. Endometrial hyperplasia clinical feature - postmenopausal bleeding in >90% cases Pathology Endometrial carcinoma is divided into two subtypes - type I and type II. The majority are adenocarcinoma. Type I endometrial carcinoma favourable outcome Type II endometrial carcinoma Type I (80%) arises in the setting of unopposed Type II (20%) arises in the setting of endometrial Superficial serosal implants of endometriosis hyperestrogenism and endometrial hyperplasia. atrophy. In obese women between 55 to 65 years old. In females between 65 to 75 years old, and Well-differentiated slow growing tumor. more favourable endometrial intraepithelial carcinoma. p53 key concern More favorable outcome. v type 2 p53 mutation occurs in up to 50%. PTEN gene mutation occurs in 30-80% of cases. Poorly differentiated invasive tumours often present with metastasis (LN and distant) Poorer prognosis compared to type I lesions. liver, lungs and intestine + diaphragm INVESTIGATIONS examine uterus Transvaginal U/S take out small Hysteroscopy (video link below)guided biopsy fibroid suspect fibroid Endometriosis infiltrating the rectum Hysteroscopic Fibroid Removal.mp4 Vinod Gopalan, Pathology, School of Medicine, Griffith University UTERUS- PATHOLOGY key sign of metastasis hysterectomy - ensure no damage done to ureters ureter under the umbilical artery ENDOMETRIAL CANCER in the cardinal ligament Hysterectomy total +/- cervix taken - uterus and cervix metastasis sites Superficial serosal implants of endometriosis Radiological Pathology- Endometrial cancer Radiological Pathology- Endometrial cancer metastasis Uterine mass extending beyond pelvis ureter under the uterine arteries - can be damaged Which LN usually get affected ? Cannonball lesions - metastasis spread outside uterine space, some lymph nodes affected widened mediastrium superiorly due to mediastinal nodes Endometriosis para-aorticinfiltrating nodes, more rectum internal iliacEndometriosis the commonly infiltrating and external iliac + common aceletasis - superimosed in right mid zone the bladder Vinod Gopalan, Pathology, School of Medicine, Griffith University  FALLOPIAN TUBE Salpingitis- caused by infections (Eg- Chalmydia) Ectopic pregnancy- Always in diseases ? implantation in fallopian tube rather than uterine wall rupture - medical emergency Endometriosis- Tubal adhesions Carcinomas- Type? adenocarcinoma as columanr epithelium - tubular structure Pelvic inflammatory disease: Is a polymicrobial infection in women characterised by inflammation of the upper genital tract including endometritis, salpingitis, pelvic peritonitis, and occasionally leading to a tubo-ovarian abscess. liver capsule adhesions from pelvic inflammatory disease more than one microbial agent a - utereus inflame fallopian tube b - fallopian tube R c - pus in pouch of Douglas d - Ovary (left) arrow - pus Fitz-Hugh-Curtis syndrome: Peri-hepatitis in PID Pelvic inflammatory disease capsular infiltration with PID Identify A-D and arrows differentiation - chronic manifestation acute pelvic pain cervical motion tenderness vaginal discharge https://www.melakafertility.com/my_book/chapter-30- laparoscopic-surgery-for-pelvic-inflammatory-disease/ Vinod Gopalan, Pathology, School of Medicine, Griffith University  pus or fluid Pelvic inflammatory disease: Cogwheel Sign: lots of oedema in folds Waist Sign: The cogwheel sign refers to the pelvic imaging Color Doppler ultrasound image of the right adnexa appearance of dilated loops of fallopian tube seen in shows a tubular, avascular, cystic structure with a cross-section. It represents infolding projections “waist” (arrows), consistent with a hydrosalpinx. (sometimes looking like nodules) into the fallopian tube Abdominal Radiology volume 46, pages2985–2986 (2021) lumen which are likened to that of a cogwheel. The sign is typically described on ultrasound and is suggestive fibrotic change of tubal inflammation in pelvic inflammatory disease with a pyosalpinx or a hydrosalpinx. fluid accumulation Vinod Gopalan, Pathology, School of Medicine, Griffith University Abdominal Radiology volume 44, pages3486–3487 (2019)  projections into lumen from fibrotic change fluid in fallopian tube endometriosis, PID... OVARY Cysts- common cysts ? inclusion cyste, follicular cysts and luteal cysts follicular - granulosa cells Polycystic ovarian syndrome luteal - corpus luteum, not transition to corpus albicans epithelial neoplasms - most ovarian tumours Tumours- Neoplasms of epithelial origin account for the great majority of ovarian tumors and, in their malignant forms, account for almost 90% of ovarian cancers. Germ cell and sex cord–stromal cell tumors are much less frequent(20% to 30% of ovarian tumors). Ovarian neoplasms. Type I tumors progress from benign tumors through cystic type 1 borderline tumors that may give rise to a low-grade low grade from cystic adenomas carcinoma. Type II tumors arise from inclusions cysts/fallopian tube epithelium via intraepithelial precursors that are often not identified. They demonstrate high-grade features and are most commonly of serous histology. STIC, serous tubal intraepithelial carcinoma. Clinical features: Pain, gastrointestinal complaints, urinary frequency inclusion, high grade close to bladder or intestine cyst adenomas Serum marker for ovarian cancers: CA-125* most positive more aggressive Vinod Gopalan, Pathology, School of Medicine, Griffith University OVARY Inclusion cyst Follicular cyst Non-neoplastic ovarian cysts 1. Inclusion cyst: Derived from entrapped portions of the ovarian surface epithelium. inflammatory change inclusion - from surface epithelium 2. Follicular cyst: Cysts lined by granulosa cells. 3. Luteal cyst: Derived from corpus luteum that has not undergone the normal transition to a corpus albicans. no degeneration Luteal cyst Ep- Cuboid epithelium G- Granulosa cells endometrioid L- Luteal cells from corpus luteum Vinod Gopalan, Pathology, School of Medicine, Griffith University OVARY Polycystic ovarian syndrome It is a complex endocrine disorder characterized by hyperandrogenism, menstrual abnormalities, polycystic ovaries, chronic anovulation, and decreased fertility. migmentation thickened and Commonly seen after menarche in teenage girls or young dark skin adults who present with oligomenorrhea, hirsutism, infertility, and sometimes with obesity. The ovaries are usually twice the normal size, gray-white with a smooth outer cortex, and studded with subcortical cysts 0.5 to 1.5 cm in diameter. The Yale journal of biology and medicine 93(4):529-537 Ovarian Drilling- laparoscopic- Video-Click laparoscopic probe localised to fallopian tube bilateral PCOS removing ovary multiple cysts remove fluid and relieve fliud Vinod Gopalan, Pathology, School of Medicine, Griffith University MRI- Pathology: Ultrasound Pathology: Both ovaries are enlarged in size; The transvaginal ultrasound images show averaging 20 cc for each. Both multiple follicles in each ovary, probably in showed numerous small immature excess of 10 on each side. The ovaries were follicles (>12 in number). borderline-enlarged. consider Rotterdam criteria 1 - Abdominal US - cysts >12 several cysts 2 - hyperandrogenism cervical cyst 3 - menstural abnormailities multiple cysts Microscopic Pathology: Multiple follicular cysts in the cortex multiple follicular cysts extending into the medulla. in ovary Ovarian capsule- Thick and fibrotic Follicles- Cystic changes lined by granulosa cells. Absence of corpus leutea OVARY Chocolate cyst chocolate cyst - ovary Chocolate cysts are endometriotic cysts (endometriomas)-localized form of endometriosis and are usually within the ovary. Diagnosed via ultrasound and radiography. Symptoms vary* pelvic pain, abdominal distention dysmenorrhea, dyspareunia and infertility heme break down - like chocolate Int J Case Rep Images 2018;9:100927Z01AA2018. biopsy not diagnostic Why are they having brown fluid? ultrasound and radiology repeated bouts of haemorrhage may convert ovary into a cyst filled with brown material (chocolate cyst) Chocolate cyst- Video Vinod Gopalan, Pathology, School of Medicine, Griffith University  Shading sign OVARY Chocolate cyst T1 weighted image shading sign ovarian cyst US Pathology- Large right adnexal cystic lesion with homogeneous echogenic content. SHADING INDICATES endometrioma Radiological Pathology- shading sign Uterus- fibroid Right ovary- cyst - endometrioma T2 weighted image Left ovary- simple cyst Shading sign hypointense in T2 Vinod Gopalan, Pathology, School of Medicine, Griffith University  change in density diagnostic of Fibroid chocolate cyst cystic mass - endometrioma or chocolate cyst simple cyst  CASE STUDIES Vinod Gopalan, Pathology, School of Medicine, Griffith University CASE STUDY- 1 A 26-year-old woman was rushed to the emergency room with severe abdominal pain. Imaging studies showed a distended left fallopian tube with a mass inside. Vinod Gopalan, Pathology, School of Medicine, Griffith University ▪ Exploratory laparotomy was performed and the left fallopian tube was removed. ▪ Based on the macroscopic appearance, what are the differential diagnosis? 1 - abscess - infection 2 - hematoma - intratubal 3 - tubal pregnancy 4 - rare carcinoma Vinod Gopalan, Pathology, School of Medicine, Griffith University Virtual Microscopy Example of a ruptured tubal pregnancy Ectopic pregnancy in a fallopian tube that was excised. This is a medical emergency because of the sudden rupture with hemoperitoneum. key risks are rupture and haemorrhage Vinod Gopalan, Pathology, School of Medicine, Griffith University What other investigations you would have done before operating on the patient ? ▪ Pregnancy test ▪ β-hCG Ectopic pregnancy is a potential medical emergency, and, if not ▪ Trans-vaginal ultrasound treated properly, can lead to death. ▪ Laparoscopy ▪ Culdocentesis peritoneal fluid is obtained from the cul de sac of a female patient introduce spinal needle in vaginal wall into peritoneal space of Pouch of Douglas Key histopathological findings: 1- Embryo implanted in the fallopian tube 2- Features of the embryo (Chorionic Villi) Vinod Gopalan, Pathology, School of Medicine, Griffith University  CASE STUDY- 2 ▪ A 29-year-old woman presents to you complaining of severe pelvic cramps during menstruation. The pain radiates to her lower back. ▪ On further questioning she tells you that she also had pelvic pain during intercourse for the last 4 months. ▪ Physical examination revealed tenderness in the lower abdomen. ▪ You decided to perform a laproscopy. Vinod Gopalan, Pathology, School of Medicine, Griffith University CASE 2 MRI: Endometrial deposits on the peritoneal mesentery. Laparoscopy: Endometrial deposits on the peritoneal mesentery. Vinod Gopalan, Pathology, School of Medicine, Griffith University The mass was removed laparoscopically. Vinod Gopalan, Pathology, School of Medicine, Griffith University Key histopathological finding: 1- Endometrial glands and stroma located outside the uterus 2- Reactive fibrosis secondary to endometriosis 3- Mucinous secretions from the endometrial glands http://www.humpath.com/spip.php?article11117 Vinod Gopalan, Pathology, School of Medicine, Griffith University What are the other possible sites for endometriosis ? What do we call endometriosis if it occurs within the myometrium ? Answer: Adenomyosis Excision of Endometrial tissue- Video-Click Vinod Gopalan, Pathology, School of Medicine, Griffith University SELF ASSESSMENT What are the likely pathophysiology behind endometriosis ? 1 - regurgitation theory: retrograde menstruation 2 - benign metastasis theory: via blood vessels and lymphatics 3 - metaplastic theory: mesothelium to endometrium 4 - stem/progenitor theory: circulating stem cells from bone marrow to endometrium In endometriosis, how does the endometrial tissue survives in ectopic organs endometrial stromal cells secrete aromatase and produce oestrogen Treatment options in endometriosis COX-2 inhibitors and aromatase inhibitors Vinod Gopalan, Pathology, School of Medicine, Griffith University CASE STUDY 3 ▪ A 32-year-old married woman presents to your complaining of urinary frequency and frequent profuse menstrual periods. ▪ She was trying to conceive for the last 3 years without success. ▪ On examination, she had pale hands and conjunctivae. You also find a firm abdominal mass in her pelvic region. ▪ What investigations would you order ? Pelvic ultrasound Vinod Gopalan, Pathology, School of Medicine, Griffith University A very large fibroid on pelvic ultrasound. Fibroids on CT-Pelvis. Vinod Gopalan, Pathology, School of Medicine, Griffith University  Bleed the most pedunculated Vinod Gopalan, Pathology, School of Medicine, Griffith University Treatment: -Medication Some forms of fibroids -Ultrasound guided destruction of the tumor. can metastasize without -Myomectomy/Hysterectomy. malignant transformation. Vinod Gopalan, Pathology, School of Medicine, Griffith University Vinod Gopalan, Pathology, School of Medicine, Griffith University Key histopathological findings: 1. Proliferation of smooth muscle fibres in whorled pattern (spiral) 2. Absence of malignant features Vinod Gopalan, Pathology, School of Medicine, Griffith University CASE STUDY-4 A 34-year-old woman presented with itch and soreness in her vulvar region. She is a sex worker and has a history of chronic smoking. Inspection- A whitish non-ulcerative lesion was noticed on the labia majora Inguinal lymph nodes- not palpable Differentials ? 1 - lichen sclerosis 2 - lichen simplex chronicus 3 - VIN 4 - carcinoma 5 - paget disease Vinod Gopalan, Pathology, School of Medicine, Griffith University ▪ A biopsy was performed. Histopathological features are shown below (click for live microscopy) evidence of VIN Key histopathological finding: 1- Severe dysplasia of the squamous epithelium 2- Pleomorhism and lack of differentiation between matured squamous cells and immature basal cells Vinod Gopalan, Pathology, School of Medicine, Griffith University What are the risk factors of cervical intraepithelial neoplasia ? HPV types 16, 18, 31, 33 and 45, amongst others. Multiple sexual partners Risk factors (3 major) Smoking 1, HPV infection Immunodeficiency 2, Immunodeficiency 3, Conception before age 17 What is the most important complication ? Squamous cell carcinoma- invasive Vinod Gopalan, Pathology, School of Medicine, Griffith University CASE STUDY 5 Julie, a 38 year old school teacher and she is 5 month pregnant. She is complaining of painless vaginal bleeding for last few days. During her first trimester Julie had more vomiting than expected. On examination, her uterus was larger than expected. You decided to order an ultrasound and blood hCG. Ultrasound revealed a bunch of grapes (honeycombed uterus) like lesions in the uterus suggestive of hydatidiform mole (molar preganancy) Vinod Gopalan, Pathology, School of Medicine, Griffith University Surgical curettage was performed and samples were send for histopathological examination. open and widen cervix - remove some material, foreign contents https://link.springer.com/article/10.1007/s00261-016-1008-0 Key histopathological finding: - Increased trophoblast proliferation - Enlargement of chorionic villi (Avascular) - Formation of cisterns Vinod Gopalan, Pathology, School of Medicine, Griffith University Hydatidiform mole Key Clinical characteristics ▪ Definition- voluminous mass with cystic swelling and grossly appear as grape-like structures ▪ Molar lesions are divided into partial, complete and invasive Hydatidiform moles ▪ Complete: Not compatible with embryogenesis and rarely contain fetal parts ▪ Partial: Compatible with embryogenesis and may contain fetal parts. ▪ Invasive: Complete moles with invasion/penetration into uterine walls. non molar disease - choriocarcinomas and rare trophoblastic malignancies gestational trophoblastic disease sperm and empty egg Vinod Gopalan, Pathology, School of Medicine, Griffith University  A SELF ASSESSMENT Histopathological features of two breast cancer tissues (A and B) are shown here Which of these patients (A or B) B show features of invasive ductal carcinoma B Features of calcification is seen in (A or B) B Vinod Gopalan, Pathology, School of Medicine, Griffith University SELF ASSESSMENT Likely pathology ? non invasive hydaliform mole no sign of fetal material complete mole Vinod Gopalan, Pathology, School of Medicine, Griffith University SELF ASSESSMENT A Female genital tract Identify the tissue of origin ectocervix/vagina Zonal differentiation is absent in image________ A B HPV 16 antibody is likely to be positive in image ________ A Vinod Gopalan, Pathology, School of Medicine, Griffith University  Thank You Email: [email protected] Phone: 0756780717 Location: G40, Room- 8.33. Vinod Gopalan, Pathology, School of Medicine, Griffith University  SELF STUDY RESOURSES https://doi.org/10.3892/mco.2018.1719 Preoperative findings of invasive Paget's disease of the vulva. (A) Macroscopic appearance of the vulvar tumor. A red mass measuring 4.3×3.6 cm near the clitoris and a widespread erythematous rash in the vulva were observed. (B) Enlarged bilateral superficial inguinal lymph nodes (arrowheads) were observed on computed tomography scan. (C) Enlarged left obturator and lateral supra-inguinal lymph nodes (arrowheads) were visualized using computed tomography. (D) On positron emission tomography, fluorodeoxyglucose uptake (arrowheads) was observed in the left obturator and lateral supra-inguinal lymph nodes, as well as the vulvar tumor. Vinod Gopalan, Pathology, School of Medicine, Griffith University SELF STUDY RESOURSES Focal adenomyosis: a Axial T2- and b Axial T1 3D FS-weighted images, showing embedded bright foci on T2- and T1 3D FS-weighted images representing haemorrhagic foci (white arrows) Vinod Gopalan, Pathology, School of Medicine, Griffith University  SELF STUDY RESOURSES ANTEMORTEM DIAGNOSIS OF CYSTIC ENDOMETRIAL HYPERPLASIA (Journal of Zoo and Wildlife Medicine, 46(4), 904-908,) Not in Human Vinod Gopalan, Pathology, School of Medicine, Griffith University  SELF STUDY RESOURSES https://www.webpathology.com/image.asp?case=524&n=1 Chocolate Cysts in ovary. The patients are usually of child-bearing age and present with infertility and cyclical pain associated with menstruation. Repeated bouts of hemorrhage may convert ovary into a cyst filled with brown material (chocolate cyst) Vinod Gopalan, Pathology, School of Medicine, Griffith University