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. 2020 Oct-Dec;61(4):985-997.
doi: 10.47162/RJME.61.4.01.

Ovarian ectopic pregnancy: the role of complex morphopathological assay. Review and case presentation

Anca Maria Istrate-Ofiţeru  1 , Dan Ruican, Mihaela Niculescu, Rodica Daniela Nagy, Gabriela Camelia Roşu, Ana Maria Petrescu, Roxana Cristina Drăguşin, Larisa Iovan, George Lucian Zorilă, Dominic Gabriel Iliescu
Affiliations

Ovarian ectopic pregnancy: the role of complex morphopathological assay. Review and case presentation

Anca Maria Istrate-Ofiţeru et al. Rom J Morphol Embryol. 2020 Oct-Dec.

Abstract

Ovarian ectopic pregnancy (OEP) represents the rarest type of ectopic pregnancy, accounting for 1-3% of this pathology. The diagnosis of this pathology is challenging due to the non-specific clinical aspects and the ultrasound examination hampered by the lack of visible gestational sac in the presence of hematocele and hemoperitoneum. The purpose of the extended histopathological (HP) examination was to identify particular aspects of the OEP trophoblast and to highlight potential local ovarian modifications which can determine pregnancy fixation at this level. The patient presented local favorable conditions for intraovarian nidation, conditions confirmed by the HP classical examination and by the immunohistochemical evaluation. We identified, using classical Hematoxylin-Eosin, Masson's trichrome and Periodic Acid-Schiff (PAS)-Hematoxylin, necrotic hemorrhage, accentuated vascular thrombosis and high density lymphoplasmocytary infiltrate. These modifications increased local adhesivity and cell destruction through hypoperfusion. Anti-cluster of differentiation antibodies (CD34, CD38, tryptase) revealed the low number of intravillous vessels and the high number of macrophages and mastocytes involved in the local inflammatory process heighten. We identified the presence of trophoblast tissue in the ovarian structure using anti-cytokeratin AE1∕AE3 (CK AE1∕AE3)/anti-cytokeratin 7 (CK7) antibodies. The anti-alpha-smooth muscle actin (α-SMA) and anti-vimentin (VIM) antibodies displayed the density of myofibroblasts and intravillous stromal cells and with the aid of anti-progesterone receptor (PR) antibody, we identified the corpus luteum hormonal response in the OEP. The placental villosities present a blocked multiplication process at the anti-apoptotic B-cell lymphoma 2 (BCL2) protein, confirmed by the Ki67 cell proliferation and tumor protein 63 (p63) immunomarkers. Anti-neuron specific enolase (NSE), anti-calretinin and anti-inhibin A antibodies showed the particular aspects of the granulosa and internal theca cells, which may be involved in oocyte release blockage, intraluteal and extraluteal fecundation of the OEP.

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Conflict of interest statement

The authors declare that they have no conflict of interests.

Figures

Figure 1
Figure 1
Ultrasound assessment during the consultation in the Emergency Room: (A) Uterus surrounded by peritoneal content, with the appearance of free clear fluid posteriorly and complex mass with coarse echoes, suggesting hematocele, in front of the uterus – note the thickened decidualized endometrium (open star); (B) Free clear fluid and dense free fluid surrounding the uterus, suggesting a significant amount of hemoperitoneum; (C and D) Irregular heterogenous mass (open arrow) projecting from the left ovary contour, with hypodense content and communicating with the peritoneal free fluid
Figure 2
Figure 2
Intraoperative images: (A) Massive hemoperitoneum and left ovary solution of continuity with adherent clots, continuing with the hematocele; (B) Exteriorization of left adnexa after the aspiration of the blood and clots – normal left uterine tube and left ovary with a violaceus, eccentric mass, covered with adherent cloths and a large, crateriform solution of contiguity; (C) The ovary is clamped in healthy tissue, the mass is excised with safety margins; (D) Interrupted suture at excision level; (E) Right tube and ovary with normal appearance; (F) The excised ovarian tissue with an area of healthy margin marked with an arrow. (G) Postoperative macroscopic aspects
Figure 3
Figure 3
(A) Bitrophoblastic mesenchymal placental villi with syncytiotrophoblast on the outside and cytotrophoblast on the inside, with hypercellular and hypovascular appearance; (B) Hemorrhagic necrosis and extravillous diffuse interstitial and gigantocellular trophoblast. Classical Hematoxylin–Eosin (HE) staining: (A) ×100; (B) ×40
Figure 4
Figure 4
(A) Extravillous gigantocellular and interstitial trophoblast at the bottom of the image, and at the top of the image, luteal cells and periluteal and intraluteal lymphoplasmocytary inflammatory cells; (B) Extravillous trophoblast, mesenchymal young bitrophoblastic villosities and at the bottom of the image a partial denudated by cytotrophoblast and syncytiotrophoblast hypocellular/hypovascular villosity – in the bottom left, image presents a trophoblastic polar proliferation. Classical Hematoxylin–Eosin (HE) staining: (A and B) ×100
Figure 5
Figure 5
(A) Extravillous trophoblast, mesenchymal young bitrophoblastic villosities and in the bottom part of the image a partial denudated by cytotrophoblast and syncytiotrophoblast hypocellular/hypovascular villosity – the bottom left part of the image presents a trophoblastic polar proliferation; extravillous trophoblast with extensive areas of hemorrhagic necrosis cand be observed; this can be explained by changes caused by thrombophilia and possible intravascular disseminated coagulation; (B) Thrombosed vessels and perivascular lymphoplasmacytic infiltrate – in the right part of the image is observed an area of hemorrhagic necrosis and in the left part thecal layer of corpus luteum; (C) In the center of the image are identified granular cells and in the periphery of the image, around the granular cells, polygonal cells representing the sheath of the ovary. Classical Masson’s trichrome (MT) staining: (A) ×40. Periodic Acid–Schiff–Hematoxylin (PAS-H) staining: (B and C) ×100
Figure 6
Figure 6
(A) Granular cells disorganized by the hemorrhagic area, usually positive at cytoplasmatic level; (B) The positive reaction at extracellular extravillous gigantocellular and bitrophoblastic villous trophoblastic level. IHC staining with anti-CK AE1/AE3 antibody: (A and B) ×100. CK AE1/AE3: Cytokeratin AE1/AE3; IHC: Immunohistochemical
Figure 7
Figure 7
(A) Positive cytotrophoblast intracytoplasmic reaction and negative at syncytiotrophoblast level – this positive result represents a factor that confirms the ovarian localization of the extrauterine pregnancy; positive reaction at granular cell lever, disorganized by the hemorrhagic necrosis; (B) Positive reaction at the corpus luteum level, in the endothelial vascular cells – corpus luteum is situated in the middle of the image, the granular and luteinized thecal cells present rare killer (K) cells at the demarcation between the two layers. IHC staining with anti-CK7 antibody: (A) ×100. IHC staining with anti-CD34 antibody: (A) ×100. CD: Cluster of differentiation; CK7: Cytokeratin 7; IHC: Immunohistochemical
Figure 8
Figure 8
(A) Focal positive reaction in the sheath of the corpus luteum and highly positive in the granulosa; (B) Highly positive mesenchymal cells inside the young or mesenchymal placental villi, but also in areas of hemorrhagic necrosis. IHC staining with anti-α-SMA antibody: (A) ×100. IHC staining with anti-VIM antibody: (B) ×100. α-SMA: Alpha-smooth muscle actin; IHC: Immunohistochemical; VIM: Vimentin
Figure 9
Figure 9
Weak positive reaction in periphery thecal cells and intense positive reaction in granular cells located centrally. The reaction is negative in the mesenchymal placental villi weakly positive. IHC staining with anti-PR antibody, ×100. IHC: Immunohistochemical; PR: Progesterone receptor
Figure 10
Figure 10
(A) Positive reaction in cytotrophoblastic cells and negative reaction in syncytiotrophoblast cells; (B) Positive reaction at nuclear level in cytotrophoblast cells and negative reaction at nuclear level in syncytiotrophoblast cells. IHC staining with anti-Ki67 antibody: (A) ×100. IHC staining with anti-p63 antibody: (B) ×100. IHC: Immunohistochemical; p63: Tumor protein 63
Figure 11
Figure 11
(A) Positive reaction at the level of the syncytiotrophoblast, which confirms that during villous evolution the cytotrophoblast will disappear through apoptosis; (B) Positive reaction at the level of the interstitial and gigantocellular extravillous trophoblast and luteal cells. IHC staining with anti-NSE antibody: (A) ×100. IHC staining with anti-BCL2 antibody: (B) ×100. BCL2: B-cell lymphoma 2; IHC: Immunohistochemical; NSE: Neuron-specific enolase
Figure 12
Figure 12
(A) Positive reaction for macrophages at interstitial extravillous trophoblast level; (B) Positive reaction for mastocytes, arranged predominantly perivascular. IHC staining with anti-CD68 antibody: (A) ×100. IHC staining with anti-tryptase antibody: (B) ×100. CD68: Cluster of differentiation 68; IHC: Immunohistochemical
Figure 13
Figure 13
(A) Positive reaction for individual stromal cells, luteinized internal thecal cells and negative reaction for granular cells and external thecal cells; (B) Positive reaction for thecal cells and negative reaction for central granular cells. IHC staining with anti-calretinin antibody: (A) ×100. IHC staining with anti-inhibin antibody: (B) ×100. IHC: Immunohistochemical
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