Strategy for a large multinodular goiter amid recent postoperative confirmation of a high-grade serous ovarian carcinoma

1. Introduction

High-grade serous ovarian carcinoma (HGSOC) has the highest frequency among ovarian cancer types and the worst prognosis, at the same time^(1-3). HGSOC accounts for 75% of ovarian carcinomas and has a median age of diagnosis of 60-61 years old^(4-6). Although recognition usually occurs in later stages, the development of cancerous site begins decades before in the fallopian tube^(7,8). This provides the opportunity of discovering advanced diagnostic instruments in order to detect serous tubal intraepithelial carcinomas which are the precursor lesions of HGSOC, and proceed to surgery at an early stage of tumor evolution^(9,10).

On the other hand, multinodular goiter has a larger epidemiologic impact, regardless of the high prevale­nce of autoimmune thyroid background in modern era, particularly in adult females. Large glands or compressive elements as well as suspected malignancy require prompt thyroidectomy that nowadays represents a standard care, with a good early and distant postoperative outcome and short hospitalization stay, including in cases with voluminous masses^(11-13).

However, there are some data showing that ova­rian cancer might be associated with thyroid nodular (malignant and benign) conditions, probably based on common genetic background (involving a syndromic presentation or not; for instance, DICER pathogenic variants or Cowden syndrome, etc.)^(14-16).

We aim to present the case of a lady admitted for a recent surgery concerning a severe form of ovarian malignancy in association with a voluminous multinodular goiter.

2. Case report

A 65-year-old female patient was referred for thyroid evaluation of a multinodular goiter that developed more than 10 years before; this admission was done as an emergency, after she recently had surgery for an ovarian cancer in order to safely receive her second-line therapy. She had no compression symptoms at the moment of evaluation. Her medical history included large bilateral ovarian tumors detected at pelvis magnetic resonance imaging (MRI) a few months before, followed by total hysterectomy and bilateral adnexectomy (Figure 1).
 

Post-surgery pathological examination revealed a right ovary of 6 by 3.5 by 2 cm, with multiple cystic cavities with a maximum diameter of 5 cm and mucinous composition, and a left ovary of 17 by 13 by 6 cm with multilocular spaces filled with serous fluid and multiple formations, diagnosing a bilateral high-grade ovarian serous carcinoma with predominantly solid and papillary pattern, classified as pT1c3 pNx cMx, FIGO IC stage. Immunohistochemistry evaluation was also performed, resulting in a Ki67 index of 80% (Table 1).
 

On admission, the biochemical assessment revealed normal liver and renal function, and glycated hemoglobin A1c at the upper limit of the normal range, however with normal fasting glycemia (Table 2).
 

Thyroid panel revealed a mildly decreased thyroid stimulating hormone and FT4 (free levothyroxine) within normal range, with negative anti-thyroperoxidase and anti-thyroglobulin antibodies, as well as TRAb (anti-TSH receptor antibodies). No anomalies were found regarding FSH (follicule stimulating hormone), LH (luteinizing hormone), estradiol and testosterone levels (in relationship with her menopausal status). Tumor markers calcitonin, CEA (carcinoembryonic antigen) and CA 125 (cancer antigen 125) were also normal (Table 3).
 

Mineral metabolism evaluation detected hypovitaminosis D and elevated bone formation marker P1NP and serum bone resorption marker CrossLaps (Table 4).
 

Thyroid ultrasound showed a right lobe of 3.2 by 2.2 by 4.9 cm and a left lobe of 2.7 by 2.3 by 6.2 cm, with hypoechoic, inhomogeneous pattern; the lower half of the right lobe had a hypoechoic, inhomogeneous conglomerate, vascularized, with macrocalcifications with posterior acoustic shadowing of 2.5 by 1.8 by 1.8 cm; the isthmus had a hypoechoic nodular conglomerate with necrosis areas of 4.7 by 1.7 by 4.64 cm, with extension to the left lobe and occupying the lower part (TIRADS 4c-5); the upper half of the left lobe displayed a hypoechoic, inhomogeneous nodule with microcalcifications of 1.3 by 1.3 by 1.4 cm and another nodule with calcifications and posterior acoustic shadowing, with a tendency to conglomerate with the previous one, of 3 cm (TIRADS 5); lymphadenopathy with microcalcifications with posterior acoustic shadowing of 1 by 0.8 by 0.54 cm left laterocervical and another similar lymphadenopathy of 0.5 by 0.4 cm right laterocervical (Figure 2).
 

Intravenous contrast computed tomography of the cervical region revealed a right thyroid lobe of 3.07 by 3.98 by 6.43 cm, left thyroid lobe of 2.8 by 3.11 by 3.29 cm, and an isthmic nodule of 3.33 by 2.24 cm, enhancing, heterogeneous, right lobe nodules of 2.02 by 2.49 cm and 1.7 by 2.22 cm, respectively, and a left lobe nodule of 1.14 by 1.29 cm. Thorax evaluation detected that a mass from the thyroid was also extended and visible in the superior mediastinum, a right lateral pleural nodule with bosselated margin in the posterior segment of the right upper lobe of 1.08 by 1.98 by 2.01 cm, and microadenopathy in the right and left hilum and in the superior and middle mediastinum; the pelvis region confirmed total hysterectomy, with no subdiaphragmatic lymphadenopathies and thin fluid collection in the pouch of Douglas. Overall, the tracheal diameter was not affected in order to impose an emergency thyroidectomy. A multidisciplinary decision was taken to postpone thyroid removal so that the patient can start chemotherapy as a priority due to the post-surgery pathological report. Close imaging and hormonal surveillance are required, along with active intervention in case of increase dimensions. Alternatively, a fine needle aspiration at the largest thyroid nodule was proposed, but declined by the patient.

3. Discussion

All patients who underwent surgery for HGSOC must follow adjuvant chemotherapy, in contrast with other ovarian cancer subtypes which require treatment scheme corresponding to the stage of the disease^(17,18).

A perspective for improving these patients’ outcome is the focus on poly (ADP-ribose) polymerase (PARP) inhibitors as targeted therapy for patients who relapse after adequate chemotherapy in the front line^(19,20). Cytoreductive surgery had already been performed in this patient’s case, and chemotherapy was recommended as adjuvant treatment before she came for endocrine check-up. Although TI-RADS classification of the nodule indicated a high risk of thyroid cancer requiring total thyroidectomy and lymphadenectomy, the initiation of adjuvant therapy for ovarian cancer was considered a priority^(21,22).

Additional observation is represented by the low Body Mass Index of the patient (16.5 kg/sqm) that seemed constitutional rather than related to the recent gynecological surgery. Body Mass Index is controversially associated with the outcome in this severe malignancy^(23,24). Also, the patient had a low normal TSH that might require supplementary follow-up in order to avoid a clinically manifested hyperthyroidism. Of note, she had low vitamin D levels which have been reported in correlation with various conditions, oncologic or not, but, at this point, it seemed incidental^(25-28).

4. Conclusions

While genetic exploration seems less likely useful in this particular instance, the connection between a severe type of ovarian cancer and a multinodular goiter should be carefully taken into consideration for practical purposes in order to decide the best intervention strategy and which step of multidisciplinary approach to be prioritized.  

 Corresponding author: Florica Şandru, e-mail: florysandru@yahoo.com

CONFLICT OF INTEREST: none declared.

FINANCIAL SUPPORT: none declared.

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