The Cystic Procreant-Uterine Adenosarcoma

Introduction

Uterine Adenosarcoma is an exceptionally discerned, malignant, biphasic, lobulated neoplasm configuring polyp- like lesions. Tumefaction is comprised of benign glandular epithelial component admixed with sarcoma component of mesenchymal origin. Uterine Adenosarcoma may exhibit overgrowth of sarcoma component, defined as a neoplasm comprised of >25% sarcomatous component. Overgrowth of pure sarcoma component within uterine Adenosarcoma comprises nearly 25% to 80% of tumour parenchyma and is associated with an aggressive clinical course. Homologous sarcomatous component is commonly incorporated within the neoplasm although heterologous elements as skeletal muscle, cartilage, foci of rhabdomyosarcoma or ovarian sex cord-like differentiation may been countered. Malignant uterine Adenosarcoma exemplifying variable quantities of rhabdoid cells is commonly associated with an aggressive biological course.

Extra-uterine Adenosarcoma incriminates younger women and exhibits an aggressive clinical course, in contrast to uterine Adenosarcoma. Up to 50% of extra-uterine lesions manifest sarcomatous overgrowth with consequently inferior prognostic outcomes and enhanced proportionate tumour reoccurrence. Besides, tumefaction may demonstrate heterologous elements as foci of rhabdomyosarcoma or leiomyosarcoma. Uterine Adenosarcoma comprises of ~8% of uterine sarcomas. Generally, postmenopausal women are incriminated. Disease emergence is commonly encountered within 14 years to 89 years with median age of disease onset at 58 years [1, 2]. Uterine Adenosarcoma frequently arises within the endometrium. Besides, sites such as cervix, fallopian tube, ovary or para-ovarian tissue may exemplify the neoplasm [1, 2].

Factors such as obesity, diabetes, endometriosis, adenomyosis, history of pelvic irradiation, excessive levels of serum oestrogen or therapy with tamoxifen may contribute to emergence of uterine Adenosarcoma.

Uterine Adenosarcoma demonstrates an intense nuclear immune reactivity to BCOR with expression of JAZF1-BCORL1 fusion gene. Uterine Adenosarcoma commonly exhibits JAZF1-BCORL1 genetic rearrangement along with EP300-BCORL1 or internal BCORL1 genomic rearrangement, inactivating BCORL1 chromosomal mutation and homozygous BCORL1 genomic deletion, features which are associated with aggressive clinical behaviour. Nearly 50% of uterine sarcomas with BCORL1 genetic mutation delineate CDK4 genomic amplification or deficiency of CDKN2A [1, 2]. Upon gross examination, resected neoplasm appears as solid, submucosal, well defined, greyish white and haemorrhagic with focal mucinous degeneration. Tumour magnitude is variable.

Grossly, the tan, friable tumour mass may arise from fundus and expand into the cervix [2, 3]. Upon microscopy, tumour exemplifies a dense proliferation of uniform, spindle shaped cells configuring fascicles, a distinct herringbone pattern or focal areas of leaf-like architecture with intra- glandular polypoid projections of the stroma. The biphasic neoplasm exemplifies alternating sparsely cellular and densely cellular areas intermingled within an oedematous stroma [2, 3].

Densely proliferating, uniform stromal spindle shaped cells congregate beneath the benign glandular epithelium and appear circumscribed by an oedematous stroma.

Atypical stromal cells appear permeated with irregular, oval to elliptical nuclei [2, 3].

Commonly, polypoid uterine tumefaction is superimposed with benign endometrial glandular epithelium. Subjacent cellular stroma is composed of miniature spherical cells pervaded with moderate, pale cytoplasm and spherical to elliptical, vesicular nuclei with prominent nucleoli. Focal, sub epithelial condensation of sarcomatous component may ensue. Mitotic activity is significant and figures of up to 40 mitosis per 10 high powerfields may be obtained. Tumour necrosis is frequently observed. Nuclear atypia is absent [2, 3]. Uterine Adenosarcoma with rhabdoid cells emerges as a distinct subtype and predominantly exemplifies cytoskeletal inclusions composed of intermediate filaments appearing as an eccentric, eosinophilic cell body displacing the atypical nucleus. Stromal cellular component may display disseminated sheets of rhabdoid cells permeated with abundant cytoplasm and eosinophilic inclusion bodies with laminated architecture exemplifying eccentric displacement of nuclei [2, 3]. SMARCA4 deficient uterine sarcoma devoid of the genetic mutation may demonstrate a focal leaf- like architecture with cellular infiltration into adjoining benign endometrial glands and an admixture of sheets of rhabdoid cells [3, 4]. TNM staging of uterine Adenosarcoma as per American Joint Committee on Cancer 8th edition and International Federation of Gynaecology and Obstetrics (FIGO) [3, 4].

Primary Tumour

• TX: primary tumour cannot be assessed
• T0: no evidence of primary tumour
• T1 (I): tumour confined to the uterus
• ~T1a (IA): tumour confined to the endometrium or endocervix
• ~T1b (IB): tumour infiltrates < 50% of myometrium
• ~T1c (IC): tumour infiltrates ≥ 50% of myometrium
• T2 (II): tumour extends beyond the uterus and appears confined within the pelvis ~T2a (IIA): tumour incriminates uterine adnexa
• ~T2b (IIB): tumour incriminates diverse pelvic tissues
• T3 (III): tumour infiltrates abdominal tissues or viscera
• ~T3a (IIIA): tumour infiltrates abdominal tissues within a singular site
• ~T3b (IIIB): tumour infiltrates abdominal tissues in > singular site
• T4 (IVA): tumour infiltrates urinary bladder or rectum