Case presentation

In March 2022, a 37 year old nulliparous woman with grade 2 obesity (body mass index 37 kg/m²), presented complaining of abdominal pain and pelvic mass. Her medical history began in January 2013 when a right salpingo-oophorectomy was performed for an adnexal mass. The pathology revealed an immature teratoma, grade 2, of International Federation of Gynecology and Obstetrics (FIGO) stage IIB at least (as no formal staging was performed). Due to the patient’s young age, a conservative approach was attempted, and restaging surgery was not performed. The patient received IV bleomycin 30 000 IU, etoposide 100 mg/m², and cisplatin 20 mg/m² until June 2013.

In May 2014, a pelvic relapse occurred and the patient underwent a hysterectomy, left salpingo-oophorectomy, excision of pelvic recurrence, and pelvic and para-aortic lymphadenectomy. The pathology confirmed the diagnosis of mature and immature teratoma. The patient refused any adjuvant treatment. In September 2014, multiple peritoneal and omental nodules were detected on surveillance computed tomography (CT) scan. Another laparotomy was performed, but no information on residual tumor was available, as the surgery was performed in another hospital. Chemotherapy with paclitaxel 175 mg/m², ifosfamide 2500 mg/m², and cisplatin 50 mg/m² was administered until January 2015. CT scan showed stable disease in the pelvis and no other lesions; treatment was stopped at that time.

A CT scan in June 2015 revealed multiple small lung nodules, which were interpreted as progressive disease, and treated with adriamycin 75 mg/m² until October 2015. The reassessment revealed stable abdominal disease and complete pulmonary response, and the patient was recommended routine surveillance with positron emission tomography (PET) scans and/or CT scans. She had a non-metabolic and stable disease for almost 6 years.

In March 2021, a new CT scan showed an increase in the pelvic lesion with infiltration of the recti abdominal muscles. The patient refused treatment at that time and presented to our institution in March 2022 with a progression of pelvic disease.

Dr Fagotti: What therapeutic options would you suggest for the patient at this time?

Immature teratomas are germ cell ovarian tumors that account for less than 1% of all ovarian cancers. These consist of immature embryonic structures derived from all three embryonic layers: the mesoderm, the endoderm, and the ectoderm; but mature elements can also be admixed. Approximately one-third of immature teratomas express serum α-fetoprotein.1 The prognosis is related to the FIGO stage and the grade of the tumor. The grade is based on the degree of immaturity of the various tissues. In our case, the patient had a grade 2 tumor consisting of foci of immature neuroepithelial tissue occupying 1–3 low-power fields (40 x) in any slide. The grade is considered the most important risk factor for relapse. In historical studies, the recurrence rate ranged between 18% for patients with grade 2 tumors and 70% for patients with grade 3 tumors. 2 More recently, in 81 adult patients with immature teratomas, Pashankar et al reported a lower rate of relapses, but still related to the grade of disease.3 Incomplete surgical staging is another factor that impacts the risk of relapse.3 4

Although the role of secondary cytoreductive surgery for patients with recurrent or progressive ovarian germ cell tumors remains controversial, it may have some benefits for a select group of patients, particularly those with immature teratomas.5 Indeed, in these patients, besides the risk of immature components relapse, a growing teratoma syndrome may occur. This rare syndrome consists of enlarging masses of pure mature teratomatous tissue developing after chemotherapy, with normal levels of previously elevated tumor markers.6

Growing teratoma syndrome has been estimated to occur in between 19% and 40% of women previously treated for immature teratomas. The major risk factors are advanced stage disease at the diagnosis and the administration of adjuvant chemotherapy.7 8 The abdominal masses could lead to complications such as compression of surrounding tissues, bowel obstruction and necrosis, vascular thrombi, and tumor rupture.8 These lesions are refractory to chemotherapy; consequently, surgery is the only curative treatment. Since our patient had several risk factors for growing teratoma syndrome and she was in pain, we planned a radiological assessment to evaluate the feasibility of surgical resection.

Dr Panico: What were the radiological findings of the lesion? Is there a role for radiomics in identifying immature areas or growing teratoma syndrome?

We performed an abdominal CT scan showing a large pelvic lesion (17×13×15 cm), with solid and heterogeneous components. The lesion infiltrated laterally the pelvic wall muscles and anteriorly the abdominal wall muscles, encroaching on the subcutaneous fatty tissue. Furthermore, the ureters and the posterior wall of the bladder were infiltrated, and the left ischio-pubic branch was eroded. Also, the MRI confirmed the infiltration of the pubic symphysis, of the ileo-pubic branch up to the anterior acetabular column, and of the anterior third of the ischio-pubic branch. ( figure 1A,B,C,D )

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Figure 1

A) Axial, B) coronal and C) sagittal post contrast CT scan image, D) Axial MRI T1-weighted image

Some radiological features can help to discriminate between mature teratomas, immature teratomas, and growing teratoma syndrome. Radiological features of mature teratoma at CT scan include fat attenuation within a cyst, with or without calcification in the wall. It is possible to find a fat–aqueous fluid interface due to the presence of a floating mass of hair (fat is reported in 93% of cases and teeth or other calcifications in 56% of cases). On the other hand, immature teratomas at CT scans are usually large, with an irregular solid component containing coarse calcifications and small foci of fat. To summarize, the newly developed or enlarged intra-peritoneal masses showing increased fatty components or entirely cystic lesions without a solid portion may help to suggest a diagnosis of growing teratoma syndrome.9

Radiomics is an emerging technique that transforms digital medical images into high-dimensional data through mathematical models. These data may help to investigate in a non-invasive manner the molecular properties of tumors and their biological activities. The role of radiomics features in determining benign or malignant ovarian masses has been investigated and has provided meaningful clinical endpoints, identifying tumor subregions of infiltration in epithelial ovarian cancers.10

Recently, the role of radiomics was investigated in detecting epithelial ovarian cancer from non-epithelial ovarian cancers. Combining the radiomics features and clinical factors, the overall accuracy was approximately 89.8%, which is the value achieved by frozen section analysis during intra-operative histopathologic determination.11 Although radiomics is useful to identify non-epithelial ovarian cancer, we are not yet able to distinguish between mature and immature teratoma using mathematical models.

Dr Fagotti and Dr Perisano: Could you describe the discussion regarding further management at this time?

We discussed the case in a multidisciplinary tumor board, including gynecology oncologists, urologists, orthopedics, and anesthesiologists. We agreed that the therapeutic options were limited because of the several previous chemotherapy regimens. Radiotherapy administration was not feasible because of the size of the lesion. Considering also the severe symptoms, such as abdominal pain, dysuria, and bowel obstruction, after counseling with the patient, we decided on an attempt at surgical cytoreduction. Extensive counseling was done, outlining all the possible surgical maneuvers and their potential functional consequences. One of the major concerns for the patient was the potential resection of the limbus of the acetabulum and the risk for subsequent hip joint instability.

To better tailor both accurate counseling and surgical resection, we built a 3D model of the tumor using a multiplanar restructuring and volume rendering technique. This model simplified the patient’s understanding through the direct visualization of the involved anatomical structures. The 3D reconstruction showed a full-thickness infiltration of both the superior pubic and ischio-pubic branches, without clear involvement of the acetabular surface; therefore, we were able to plan a joint-sparing surgery with an adequate free margin ( figure 2A ). The external iliac or femoral vascular axis did not demonstrate any sign of parietal infiltration; thus, there was no need to plan an iliofemoral bypass. ( figure 2B )

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Figure 2

A) 3D bone reconstruction showing a tumor full-thickness infiltration of both the superior pubic and ischio-pubic ramus, without evident involvement of the acetabular surfaceB) 3D vascular reconstruction showing no sign of infiltration of the external iliac or femoral vascular axis

In April 2022 we performed a xipho-pubic incision but we did not open the peritoneal cavity. Rather, to obtain free margins, the rectus abdominis, external oblique, and internal and transverse muscles were sectioned at the level of the macroscopic disease-free area on both sides. After vascular and nerve isolation of the iliac-femoral axis, we developed the rectovaginal septum up to the levator ani muscle, partially mobilizing the neoplastic mass. Then, after preparation of the bone surfaces for osteotomies, under fluoroscopy and with the protection of vascular-nervous structures, the orthopedic surgeon performed a pelvic resection including the ischium and pubic branches (Type III according to Enneking et al 12 ). At this point, the mass was removed en bloc with the bladder, the rectum, and the bone structures. A complete cytoreduction was obtained with no residual disease. A cutaneous uretero-ileostomy, according to the Bricker technique, 13 was performed on the right side of the abdomen. Furthermore, a sigma-rectum resection with terminus-terminal bowel anastomosis was performed.

The debulking and reconstructive surgery lasted 11 hours. Debulking was complicated by major intra-operative bleeding up to 3500 mL, due to muscle and bone resection. She received blood and plasma transfusions (nine blood units and 400 mL of plasma), but she had signs of hemodynamic instability, requiring high doses of norepinephrine. We agreed on a temporary closure of the abdomen, for the risk of new hemorrhage and a leak of the neo-bladder and bowel anastomoses. After 48 hours, a new explorative laparotomy was performed. In the abdomen, we did not find any sign of bleeding or infection; therefore, we started the closure of the abdomen, and an ABTHERA system was placed. ABTHERA is a temporary abdominal closure system, using negative pressure therapy. It provides medial tension, which helps minimize fascial retraction, and promotes the removal of abdominal fluids, preventing edema.

Despite the major surgery, the post-operative period was uneventful. She partially recovered her walking ability, as she needed a right calf brace and a Zimmer walking frame. She was discharged to a rehabilitation facility on post-operative day 15.

Dr Santoro: What were the pathology findings?

The neoplasia consisted of round-oval cells arranged in bundles and whorls. Occasional mitosis (<4 mitosis/10HPF) and scattered foci of necrosis were appreciable. The neoplasm infiltrated the bone tissue and the surrounding soft and muscle tissues, but all the surgical margins were negative. On immunohistochemical investigations, the neoplastic cells were diffusely positive for vimentin and EMA, focally positive for SSTR2A, and negative for PR, Caldesmone, Desmin SMA, CDK4, MDM2, STAT6, CD34, and Bcl2. The silver staining showed the absence of peri/intercellular reticulum. The proliferative index, evaluated by Ki67, was 10%. These results were compatible with a diagnosis of meningioma. This was unexpected, and the anatomic site and clinical history did not match completely with the origin of the neoplasm. The main hypotheses were a meningioma arising in growing teratoma syndrome (a relapse in form of a somatic tumor within a mature teratoma), or a primitive extra-cranial meningioma. ( figures 3 and 4 )

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Figure 3

: Microscopic and immunoistochemical featuresA) Proliferation of round-ovalar cells arranges in bundles and whorls (H&amp; E, 10x)B) Neoplastic cells with bland cytological alterations (H&amp; E, 40x)C) Neoplastic infiltration of the bone tissue and the surrounding soft tissues (H&amp; E, 4x)D) The silver staining showed the absence/reduction of peri/intercellular reticulum (Silver stain 20x)E-F) Neoplastic cells were diffusely positive for EMA (E, LSAB-HRP,40x) and Vimentin

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Figure 4

: Surgical specimen

Meningiomas are rare tumors originating from the arachnoid cap cells, and most occur as intra-cranial lesions. However, from 0.9–2% of cases, meningiomas can arise outside the central nervous system and are described as primitive extra-cranial meningiomas, generally clinically benign.14 They commonly present in the fifth decade, and usually affect women more than men. Among the different morphological pattern types, the meningotheliomatous form predominates at extra-cranial sites.

The most frequent site for primitive extra-cranial meningiomas is the head and neck region, but anecdotal case reports also described primitive extra-cranial meningioma localization in the pelvis.14–16 In the cases previously described in literature, the patients had a history of hysterectomy with bilateral salpingo-oophorectomy. Theories proposed to explain these unusual locations include the migration of arachnoid cells rests along cranial nerve sheaths, the proliferation of extra-dural arachnoid cells, or the growth of ectopic embryonic rests of arachnoid cells.14 15

Meningioma arising from teratoma is an extremely rare disease as well. Histogenesis can be considered as a transformation of the neurological components of mature cystic teratoma, in particular the arachnoid cells. An extensive literature search has revealed only sporadic case reports about mature cystic teratomas associated with meningioma of the ovary.17 18 To the best of our knowledge, no cases of meningioma arising from growing teratoma syndrome have been described.

Development of a secondary neoplasm in mature teratomatous tissue is a potential complication of a growing teratoma syndrome. Few previous reports described carcinoid tumors and an adenocarcinoma arising in mature teratomatous tissue of growing teratoma syndrome.19 20 Two different histogeneses have been proposed: the role of stem cells and the malignant transformation of differentiated resident cells.

Dr Fagotti: What suggestions would you have for adjuvant treatment and surveillance?

Due to the rarity of this tumor, and its unclear histopathological origin, no specific guidelines exist. We discussed the management of this case in our multidisciplinary tumor board. No diagnosis of malignancy was provided by the pathological examination, and the surgical resection was complete. Considering the multiple lines of treatment, the low chemosensitivity, the patient’s conditions, as well as her wishes, no adjuvant treatment was deemed necessary. We started a follow-up with radiological images every 3 months. Twelve months after surgery, the patient is alive, able to walk, and with no evidence of relapse at CT scan.