Krukenberg tumour in a 46-year-old black African woman with a background of ovarian fibroma- A case report

Abstract

Background

Tumours that metastasize to the ovary can occur in conjunction with other ovarian lesions, including benign sex cord stroma tumours like fibroma or fibrothecoma. This case report presents a unique instance of metastatic signet ring carcinoma involving the ovary in a background of fibroma in a Black African woman.

Patient presentation

A 46-year-old gravida 3, para 0 (2 alive), patient was referred from the general outpatient clinic to the gynecology clinic due to progressive abdominal swelling over the past eight months. Abdominal examination revealed marked distension with massive ascites. Physical examination of the chest demonstrated dullness to percussion over both lung bases, with increased dullness noted on the right. Auscultation revealed decreased air entry in the right middle and lower lung zones, with normal to increased air entry in the remaining lung fields. Abdominopelvic ultrasound revealed a large irregularly marginated homogeneous solid mass in the right adnexa measuring 16.4 × 11.7 × 12.7 cm. An abdominal CT scan revealed bilateral pleural effusion, which was more pronounced on the right, ascites, and evidence of pulmonary and hepatic metastasis. Serum chemistry revealed abnormal levels of several analytes, including elevated CA 125 at 1,108.8 (normal range 0–35) U/L and CA 19–9 at 63.8 (normal range 0–35) U/L. She subsequently underwent staging laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy, without any postoperative complications. The histologic sections of the right and left ovaries revealed a moderately cellular lesion composed of intersecting bundles of spindle cells in a fascicular and storiform pattern. Additionally, pockets of small round to oval-shaped cells with intracytoplasmic clear vacuoles pushing the nucleus to the periphery (signet ring cells) were identified in a few foci. These cells were initially thought to be ovarian stroma or theca cells. Microscopic examination revealed signet ring cells with cytoplasmic positivity for periodic acid-Schiff (PAS) staining. The histopathological diagnosis was metastatic signet ring cell carcinoma involving the ovary, with an underlying ovarian fibroma.

Conclusions

Ovarian metastatic signet ring carcinoma in a background of fibroma can pose a significant diagnostic challenge, as signet ring cells can mimic the ovarian stroma or theca cells, especially if they are only observed in a few foci of the sections.

Introduction

Krukenberg tumours are a type of ovarian tumour characterized by metastasis from primary cancers and commonly originate in the gastrointestinal tract and breast [1,2,3]. Microscopically, these tumours characteristically comprise sheets of signet ring cells featuring clear cytoplasm and eccentrically placed nuclei. However, their morphology can resemble ovarian stroma or theca cells, necessitating ancillary diagnostic tools to accurately distinguish signet ring carcinoma cells from similar cellular structures. Notably, metastatic tumours to the ovary can occur in conjunction with other ovarian lesions, including benign sex cord stroma tumours like fibroma or fibrothecoma as reported in the literature [4]. This case report presents a unique instance of metastatic signet ring carcinoma involving the ovary in a background of fibroma.

Case presentation

A 46-year-old gravida 3, para 0 (2 alive), was referred from the general outpatient clinic to the gynecology clinic due to progressive abdominal swelling over the past eight months. She complained of early satiety but denied any history of nausea, vomiting, or changes in bowel habits. Additionally, she reported a nonproductive cough, orthopnoea, and paroxysmal nocturnal dyspnoea. She had no significant past medical history.

Upon examination, she appeared chronically ill, with pallor and bilateral pitting pedal oedema extending up to the knees. She exhibited no cyanosis, jaundice, or signs of dehydration. Abdominal inspection demonstrated significant distension secondary to massive ascitic fluid accumulation, without evidence of palpable organ enlargement. Physical examination of the chest demonstrated dullness to percussion over both lung bases, with increased dullness noted on the right. Auscultation revealed decreased air entry in the right middle and lower lung zones, with normal to increased air entry in the remaining lung fields. Abdominopelvic ultrasound revealed a large irregularly marginated homogeneous solid mass in the right adnexa measuring 16.4 × 11.7 × 12.7 cm. The right ovary was not distinguishable from this lesion, and the left ovary was not visualized. The impression was a solid right ovarian mass suspicious for malignancy, accompanied by massive ascites and moderate pleural effusion with collapse of the left lower lobe. A chest radiograph confirmed moderate right pleural effusion, and pleural aspirate cytology indicated a high suspicion for malignancy. An abdominal CT scan revealed bilateral pleural effusion, which was more pronounced on the right, ascites, and evidence of pulmonary and hepatic metastasis.

Serum chemistry revealed abnormal levels of several analytes, including elevated CA 125 at 1,108.8 (normal range 0–35) U/L, CA 19 − 9 at 63.8 (normal range 0–35) U/L, CEA at 3.2 (normal range 0–5) ng/mL, LDH at 246 (normal range 225–450) IU/L, and elevated urea at 7.6 (normal range 2.5–5.8) mmol/L.

She subsequently underwent staging laparotomy with total abdominal hysterectomy and bilateral salpingo-oophorectomy, without any postoperative complications. Histopathological examination of the right and left ovaries revealed a moderate cellular lesion composed of intersecting bundles of spindle cells in a fascicular and storiform pattern. The neoplastic cells exhibited spindled to ovoid nuclei with pointed ends and scant eosinophilic cytoplasm surrounded by a collagenous stroma, with some areas showing a myxoid background. Additionally, pockets of small round to oval-shaped cells with intracytoplasmic clear vacuoles pushing the nucleus to the periphery (signet ring cells) were identified in a few foci. These cells were initially thought to be ovarian stroma or theca cells. Microscopic examination revealed signet ring cells with cytoplasmic positivity for periodic acid-Schiff (PAS) staining. The histopathological diagnosis was metastatic signet ring cell carcinoma involving the ovary, with an underlying ovarian fibroma. Figures 1, 2 and 3 show the gross and microscopic features of the mass.

She subsequently underwent abdominal paracentesis and chest tube insertion due to persistent ascites and pleural effusion, respectively. However, owing to financial constraints, she was unable to undergo further investigations and was discharged against medical advice. Additional information could not be ascertained as the patient was subsequently lost to follow-up.

Fig. 1

Gross image of the external surface of the right ovarian mass. Figure 1 above shows a bosselated surface of the right ovary

Fig. 2

Photomicrograph showing a hematoxylin and eosin-stained section of the ovarian mass. The photomicrograph shows many cells with abundant apparently clear cytoplasm and inconspicuous nuclei (signet ring cells)

Fig. 3

Photomicrograph of the mass after periodic acid–Schiff (PAS) staining. Figure 3 above shows many of the signet ring cells with pink cytoplasm

Discussion

We present a rare case of ovarian fibroma coexisting with bilateral metastatic signet ring carcinoma. Few cases of collision tumours involving ovarian fibroma have been reported in the literature, making this report noteworthy [5]. Reporting this case is crucial, as it highlights a potential diagnostic challenge that can significantly impact patient care.

The index patient presented with markedly elevated CA-125 and mildly elevated CA19-9. An increase in the serum levels of these markers, particularly in the patient’s age group, should lead to a high index of suspicion for epithelial ovarian malignancy. Although elevated CA-125 and CA19-9 levels are not pathognomonic or diagnostic of malignancy, it is essential for pathologists to thoroughly examine adequate, representative histologic sections when marker levels are increased, as some researchers have reported associations between these markers and ovarian malignancy [6,7,8]. Notably, some authors have also reported increases in carbohydrate antigens in benign ovarian lesions, highlighting the need for careful interpretation of these markers [9,10,11].

It is essential to consider a rare entity, primary signet ring cell stroma tumour of the ovary, which can mimic a metastatic tumour. Ancillary techniques are necessary to exclude this entity. Unlike our patient’s presentation, primary signet ring stroma tumours are typically benign, unilateral, and associated with normal CA-125 and CA19-9 levels. Additionally, the clear cytoplasm of these rare tumours is not stained with PAS [9, 12, 13].

Although immunohistochemistry was not performed, metastatic signet ring carcinomas typically express EMA and cytokeratins, distinguishing them from primary signet ring stroma tumours. Specifically, CK7 and CK20 staining can help differentiate between gastrointestinal origins: CK7 positivity suggests upper GI tract, while CK20 positivity indicates lower GI tract origin.

Our patient presented with a large accumulation of peritoneal fluid in the abdomen and pleural fluid in the chest. The presence of an ovarian mass was highly suggestive of a fibroma. However, since both ovaries were enlarged, other differential diagnoses need to be considered. The ascites and pleural effusion failed to resolve after removal of the ovarian masses, indicating the presence of other lesions. This failure to resolve should prompt clinicians to consider alternative diagnoses in patients initially presumed to have ovarian fibroma.

Histological examination revealed a sheet-like proliferation of bland, spindle-shaped cells with small, bipolar nuclei lacking features suggestive of malignancy. Notably, clear cells with abundant, seemingly clear cytoplasm were observed, which could be easily mistaken for theca cells commonly found in fibrothecoma. Importantly, pathologists thoroughly examine such cells, as closer inspection revealed some cells with flattened, inconspicuous, eccentric nuclei. The differential diagnosis for these clear cells includes lipoblasts, capillary endothelial cells, and signet ring cells of metastatic carcinoma.

We confirmed the nature of the cells via special histochemical stains, which are particularly useful in a resource-poor setting such as ours. The cytoplasm was positive for PAS, which strongly suggests a metastatic signet ring carcinoma, as lipoblasts and endothelial cells are typically negative for this stain.

Although immunohistochemistry can be used to identify the primary site, careful evaluation of the onset and progression of patients’ symptoms, combined with more affordable imaging evaluations, can be valuable in detecting the primary site of the disease in resource limited setting. CT scans are a valuable diagnostic tool for identifying the primary origin of metastatic tumours in low-resource settings.

In addition to the differential diagnoses mentioned earlier, it is essential to note that some uncommon tumours with signet ring morphology have been reported, including epithelioid smooth muscle neoplasms and signet ring myeloma cells [14, 15].

Conclusion

Ovarian metastatic signet ring carcinoma arising in a fibroma poses a diagnostic challenge due to the resemblance of signet ring cells to ovarian stroma or theca cells, particularly when present in limited foci. Elevated serum CA-125 and CA 19 − 9 levels in this context warrant suspicion of epithelial ovarian malignancy. Periodic acid-Schiff (PAS) staining facilitates differentiation of signet ring cells from stromal or thecal cells. Moreover, persistent peritoneal or pleural accumulation despite appropriate management should prompt reconsideration of alternative diagnoses in patients initially diagnosed with ovarian fibroma.