05/07/2018. Types of challenges. Challenging cases in uterine pathology. Case 1 ` 65 year old female Post menopausal bleeding Uterine Polyp

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1 Types of challenges Challenging cases in uterine pathology Nafisa Wilkinson Gynaecological Pathologist UCLH London Lack of complete history often, NO clinical history at all! Cases from other centres often come with incomplete information. Attitude of clinicians- testing pathologists! Rare entities not seen frequently Think laterally, show case around I have no conflict of interests to declare Case 1 ` 65 year old female Post menopausal bleeding Uterine Polyp 1

2 Case 1 Case 1 Case 1 Luminal surface scalloped and frayed Case 1 crowded glands Case 1 Mib 1 Marked cytologic atypia Marked proliferation in crowded glands 2

3 Case 1 Benign polyp with hyperplasia Mutational p53 aberrant uniform strong positive SEIC Case 1 Diagnosis : Serous endometrial intraepithelial carcinoma (SEIC) Develops on a polyp / atrophic endometrium When confined to epithelium ( SEIC) Even in absence of invasion (this is a carcinoma with potential for shedding cells and metastasising widely to extrauterine sites) Precursor lesion of HGSC Cytologic features in common to both: Nuclear enlargement Marked atypia Mitotic activity (atypical mitoses) 3

4 Prognosis Staging required Prognosis good if disease limited to endometrium Extrauterine disease associated with poor prognosis. Case 2 Case 2 continuum complex to rounded glands Case 2 72 year old female. Grade 2 endometrioid adenocarcinoma in a polyp. On MRI no obvious myometrial invasion 4

5 Case 2 Case 2 Deep myometrial invasion comprising small rounded glands with focal angulation associated with little or no stromal response Case 2 Case 2 Adenoma malignum pattern of myoinvasion associated with low grade endometrioid adenocarcinoma Round regular glands with absent or minimal stromal response 5

6 Case 2 Adenoma malignum pattern of myoinvasionof endometrioid endometrial adenocarcinoma Prognosis similar to conventionally invasive endometrioid adenocarcinoma Poor prognostic factors : deep myometrial invasion, cervical stromal involvement, higher histological grade and lymphovascular space invasion 53 year old female presented with a cervical carcinoma Case 2 Diffusely infiltrative endometrial adenocarcinoma: an adenoma malignum pattern of myo-invasion Longacre TA, Hendrickson MR Am J SurgPathol 1999;23:69-78 Low Grade, low stage endometrial endometrioid adenocarcinoma a clinicopathological analysis of 324 cases focusing on frequency and pattern of invasion Quick CM, May T, Horowitz NS, Nucci MR Int J Gynecol Pathol Jul;31(4):

7 Glandular component with eosinophilic hyaline secretion within lumina Retiform areas : branching slit like spaces with intraluminal fibrous papillae Frequent association with mesonephric hyperplasia Distinction based on -Architectural glandular crowding -Haphazard infiltrative growth -Elevated mitotic activity -Intraluminal cellular debris -Nuclear atypia 7

8 mesonephric carcinoma Immunohistochemistry CA125 + PAX 8 + GATA 3 + ER - PR - CEA- EMA + Calretinin + AE1/3 + CD10 and Vimentin +ve (apical and luminal) Rare tumours Mesonephric remnants Centred within cervical wall can extend into lower uterine segment Bulky as deeply invasive Closely packed small tubules Complex glandular architecture with intraglandular papillae Surgery Rx of choice Diagnosis: Mesonephric carcinoma Differential diagnosis Diffuse mesonephric hyperplasia Other endocervical adenocarcinoma Serous Endometrioid Clear cell 8

9 Case 4 Prognosis Rare, few cases not possible to ascertain if stage for stage prognosis differs from other variants of cervical adenocarcinoma Suggestion although indolent, propensity for late recurrence and metastasis Case 4 2 components Case 4 72 year old female PMB, endometrial ca TAH BSO Well differentiated endometrioid adenocarcinoma 9

10 Case 4 Case 4 Undifferentiated component Monomorphic sheets of cells Poor cohesion Resembles lymphoma TILS usually conspicuous Patchy positive reactivity for CD 56 Case 4 Case 4 Synaptophysin positive E cadherin loss in undifferentiated component 10

11 Case 4 mlh1 loss Case 4 Diagnosis: De-differentiated carcinoma of the endometrium with neuroendocrine differentiation De-differentiated carcinoma is composed of undifferentiated carcinoma and a second component of either grade 1 or Grade 2 endometrioid adencoarcinoma Case 4 De-Differentiated carcinoma PMS2 loss Undifferentiated component comprises small to medium dyscohesive cells of uniform size resembling lymphoma, plasmacytoma, high grade endometrial stromal sarcoma or small cell carcinoma. No gland formation seen Usually undifferentiated component lies beneath the well differentiated component which lines the uterine cavity Maybe EMA + and CK 18 (focal), Vimentin +ve, ER, PR and Ecadherin ve BRG1(SMARCA4) and/or BRM (SMARCA2) loss of expression in the undifferentiated component; 11

12 Case 5 Case 5 24 year old female, 12/12 h/o heavy menstrual loss, hysteroscopic resection of fibroids followed by hysterectomy. Was on GnRH a treatment Well circumscribed mass in anterior wall of myometrium measuring 3.0 x2.5 x 2.3 cm Gelatinous cut surface Case 5 Case 5 12

13 Case 5 ALK 1 immunoreactivity Myxoid background, inflammatory cells Diffuse ALK 1 +ve Nuclear/ Cytoplasmic Anaplastic lymphoma kinase (ALK) gene at 2p23 Case 5 Spindled to epithelioid cells Case 5 Diagnosis; Inflammatory myofibroblastic tumour 13

14 IMT Mesenchymal tumour Uterus or cervix (primary) Low malignant potential Proliferation of spindled to epithelioid cells Myxoid stromal background Prominent inflammatory (lymphoplasmacytic) infiltrate. Low mitotic rate <1/10HPF Necrosis: Infarct/degenerative Immunohistochemistry Myofibroblastic : SMA, calponin and/or desmin IMT and ALK Diagnosis Morphology correct ALK positive FISH ( -ve ) disregard as False ve FISH results Cytogenetics ALK or ROS1 re-arrangements Both Rxed with Tyrosine Kinase inhibitors IMT aggressive behaviour Size equal to or larger than 7 cm High mitotic rate (defined as 8 or more MF/10 HPF) Infiltrative borders Myxoid LMS 14

15 IMT vs Myxoid leiomyosarcoma P16 (positive in approx. 70%) : strong and diffuse P53 aberrant (50%) of cases show null pattern Not seen in IMT Case 6 Case 6 Case 6 71 year old female heavy post menopausal bleeding 15

16 Case 6 Case 6 Diagnosis :Metastatic lobular carcinoma of breast Case 6 Immunohistochemistry EMA + AE1/3 + ER + PAX 8 GCDFP-15 + GATA 3 +ve Case7 66 year old female parity 13 Cervical polyp 16

17 Case 7 Case 7 Case 7 Case 7 CK 20, CEA-M and CDX2 positive CK 7, CA125, ER and PR negative Past history of colonic carcinoma became evident on further exploration 17

18 Case 7 Diagnosis: metastatic colorectal carcinoma Acknowledgements James Bolton Rhona McVey Dahmane 18