Hemothorax resulting from hemorrhagic degeneration of giant uterine leiomyomata: A rare variant of pseudo-Meigs' syndrome.

A 40-year-old nulliparous woman taking no medications and with past medical history of only childhood asthma presented to an outlying hospital emergency department after experiencing witnessed syncope at home. She reported progressive abdominal distention over several months accompanied by moderate left lower quadrant discomfort. On initial evaluation, she had a blood pressure of 50/30 mmHg and so was resuscitated with 2 L of intravenous fluids and two units of uncrossed packed red blood cells. She was started on norepinephrine infusion. Bedside ultrasound Focused Assessment with Sonography for Trauma (FAST) examination revealed free fluid in the abdomen. She underwent computed tomography (CT) angiography of the chest, abdomen, and pelvis, which revealed a giant, conglomerate abdominopelvic soft-tissue lesion measuring 22 x 29 × 25 cm in overall size with displacement of adjacent structures ( Fig. 1 A). Imaging also revealed a small right pleural effusion and small-volume ascites ( Fig. 1 B). Laboratory tests showed a post-transfusion hemoglobin of 8.8 g/dL and a serum lactate of 7.7 mmol/L. The patient was transferred to our institution for gynecologic oncology evaluation. Fig. 1 A: Coronal reconstruction from the patient's initial computed tomography (CT) angiography of the chest performed at the outside hospital showing near-total replacement of the abdominopelvic contents by a giant, conglomerate, vascularized mass or masses with displacement of normal abdominal viscera, most notably into the left upper quadrant. Likewise present is small-volume perihepatic ascites. B: Axial image from the same CT angiogram as in panel A showing a small right pleural effusion. A small amount of right upper quadrant and left upper quadrant ascitic fluid is also noted. Fig. 1 A: Coronal reconstruction from the patient's initial computed tomography (CT) angiography of the chest performed at the outside hospital showing near-total replacement of the abdominopelvic contents by a giant, conglomerate, vascularized mass or masses with displacement of normal abdominal viscera, most notably into the left upper quadrant. Likewise present is small-volume perihepatic ascites. B: Axial image from the same CT angiogram as in panel A showing a small right pleural effusion. A small amount of right upper quadrant and left upper quadrant ascitic fluid is also noted. Following transfer, the patient was weaned off vasopressor support and her hemoglobin remained stable such that no further blood transfusions were required. There was no vaginal bleeding. Additional laboratory studies showed no detectable serum beta-hCG but did show elevated CA-125 (113 U/mL; normal 0–35 U/mL) and Human Epididymis Protein 4 (84.8 pmol/L; normal 0–63.7 pmol/L), raising concern for ovarian malignancy. Alpha-fetoprotein and carcinoembryonic antigen levels were within normal limits. Two days after transfer, she developed worsening dyspnea. CT angiography of the chest was performed and revealed no pulmonary embolism but showed a much larger right-sided pleural effusion than had been observed at presentation, with complete right lower lobe and partial right middle lobe atelectasis ( Fig. 2 A). A right-sided diagnostic and therapeutic thoracentesis was performed, yielding 1.2 L of grossly bloody fluid. Pleural fluid analysis was exudative with a hematocrit of 26 %, identical to the serum hematocrit, qualifying the effusion as a hemothorax. Cytology was negative for malignancy. Fig. 2 A: Axial image from computed tomography (CT) angiography of the chest performed at our institution showing a now-moderate right pleural effusion with compressive atelectasis. B: Axial image at the level of the pelvis from the patient's pre-operative contrast-enhanced CT showing high-attenuation ascitic fluid adjacent to part of the patient's giant, necrotic abdominopelvic mass. Fig. 2 A: Axial image from computed tomography (CT) angiography of the chest performed at our institution showing a now-moderate right pleural effusion with compressive atelectasis. B: Axial image at the level of the pelvis from the patient's pre-operative contrast-enhanced CT showing high-attenuation ascitic fluid adjacent to part of the patient's giant, necrotic abdominopelvic mass. Repeat CT of the abdomen and pelvis showed increasing abdominopelvic ascites with high attenuation (i.e., ≥50 Hounsfield units), raising suspicion for hemorrhagic ascites ( Fig. 2 B). Gynecologic oncology then proceeded with an exploratory laparotomy, which revealed 2.5 L of hemoperitoneum and several large pedunculated uterine fibroids, up to 10cm in size. A total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed with pathology showing leiomyomata with hemorrhage and infarct-type necrosis. The fibroid-containing uterus weighed 5.8kg (normal <100 gm). Cytology of the hemoperitoneum was negative for malignancy. Following the hysterectomy, there has been no recurrence of pleural or abdominal fluid for one year post-procedure.

Lawrence Huang: Writing – original draft. Tana Pradhan: Writing – review & editing. Oleg Epelbaum: Writing – original draft.

None.

The ability of peritoneal fluid to cross into the pleural space and cause a pleural effusion is well-known to pulmonologists through examples such as hepatic hydrothorax and Meigs' syndrome. The latter term, coined in the 1930s in honor of Dr. Meigs who first described the syndrome, refers to the triad of a benign ovarian mass (classically a fibroma), ascites, and a pleural effusion [ 5 ]. The definition of Meigs' syndrome also includes resolution of fluid accumulation following resection of the tumor. In subsequent years, the related entity of pseudo-Meigs’ syndrome came to encompass other gynecological neoplasms associated with concurrent ascites and pleural effusion, likewise with disappearance of fluid after surgical removal of the pelvic lesion. A spectrum of benign and malignant pelvic pathologies is associated with Meigs' and pseudo-Meigs’ syndrome ( Table 1 ) [ 6 ]. Neoplasias in the peritoneal cavity could undergo transcoelomic and/or lymphohematogenous spread to the pleural space [ 7 , 8 ]. In transcoelomic spread, cells from the primary tumor detach and seed the peritoneal fluid; following this, fluid currents can carry tumor cells cephalad across the diaphragm and directly into the pleural cavity when diaphragmatic fenestrations or porous diaphragms are present [ 9 , 10 ]. Upregulation of adhesion proteins then facilitates the implantation of these cells onto the pleural surface, leading to effusion formation. In lymphohematogenous spread, loose tumor cells traverse specialized stomata in the diaphragm and enter the lymphatic system, through which they could then migrate to distant sites through lymphatics or blood vessels, including to the pleural cavity [ 11 , 12 ]. Table 1 Pelvic pathologies associated with Meigs' and pseudo-Meigs’ syndromes. Table 1 Syndrome Tumor Type Description Meigs Syndrome Fibroma Tumors arising from the ovarian stroma that are composed of fibroblasts [ 23 ] Thecoma Estrogen-producing tumors resembling theca cells, endocrine cells groups in the ovary involved in folliculogenesis [ 24 ] Brenner Tumor Tumors from ovarian transition cells that resemble urothelial cells surrounded by dense fibrous tissue [ 25 ] Granulosa Cell Tumor Tumors derived from sex cords and ovarian mesenchyme with an indolent course [ 26 ] Pseudo-Meigs Syndrome Struma Ovarii Teratoma or the ovary that may contain functional thyroid follicles [ 27 ] Mucinous Cystadenoma Epithelial mucinous tumors that are typically unilateral, multilocular, voluminous, cystic [ 28 ] Teratoma Tumors consisting of well-differentiated derivatives of germ cell layers [ 29 ] Uterine Leiomyoma Benign uterine tumors of smooth muscle [ 30 ] Secondary Metastatic Tumors Dissemination of neoplastic cells from the primary tumor [ 31 ] Pelvic pathologies associated with Meigs' and pseudo-Meigs’ syndromes. The ability of hemoperitoneum to migrate into the pleural space is less well described, but evidence of this possibility has been available since the publication of a case series in the 1960s by Pratt and Shamblin [ 13 ] and has been reinforced by more recent reports of hemothorax in the setting of hepatocellular carcinoma rupture [ 14 ]. It is now widely recognized that simple peritoneal fluid enters the pleural space in predisposed individuals through subtle diaphragmatic defects, which can be microscopic [ 15 ]. It is likely that the same mechanism underlies the passage of blood across the diaphragm through fenestrations that in some cases could be grossly visible [ 16 ]. Uterine leiomyomata are benign smooth-muscle tumors caused by the proliferation of myometrial tissue. Typically, problems associated with these non-aggressive lesions are chronic and include vaginal bleeding, infertility, and pelvic pressure. Rarely, more serious complications can arise, one example of which is necrotic degeneration that occurs as they enlarge because the accompanying blood supply becomes inadequate, leading to infarction [ 17 ]. The subacute abdominal symptoms our patient was experiencing prior to the development of massive bleeding may have been related to progression of this phenomenon. Even less common but most acute and dangerous (a total of only 125 English-language cases published as of 2018) is the development of intra-abdominal hemorrhage, which can occur in the presence or absence of degeneration [ 18 ]. Such bleeding can initially manifest as syncope and then evolve to life-threatening hemorrhagic shock, both of which our patient exhibited. As mentioned, the first report of the triad of uterine leiomyoma, ascites, and pleural effusion was published in the 1930s, but it did not involve a hemothorax [ 19 ]. Between the 1930s and the 1970s, a number of additional reports of this triad emerged [ [20] , [21] , [22] ], some of which included hemorrhagic pleural effusion but none of which matched our scenario of proven hemoperitoneum and hemothorax in the same patient. Since the 1970s, to our knowledge there have been no analogous reports added to the English-language literature until the current one. The rarity of this type of presentation of uterine leiomyomata coupled with positivity of certain serum tumor markers understandably led to initial concern about gynecological malignancy even if hemorrhagic shock would be decidedly unusual in that setting. Ultimately, the resolution of peritoneal and pleural blood post hysterectomy qualified this case as an example of pseudo-Meigs’ syndrome brought about by very common benign pelvic masses presenting very uncommonly.

• Trans-diaphragmatic translocation of hemoperitoneum is an uncommon mechanism of spontaneous hemothorax. • Very rarely, as in our case, the culprit hemoperitoneum can result from rupture of a degenerating uterine leiomyoma. • The combination of a uterine mass, peritoneal fluid, and a pleural effusion initially raised concern for gynecologic malignancy. • The findings and outcome in our case fulfilled the definition of pseudo-Meigs’ syndrome. Trans-diaphragmatic translocation of hemoperitoneum is an uncommon mechanism of spontaneous hemothorax. Very rarely, as in our case, the culprit hemoperitoneum can result from rupture of a degenerating uterine leiomyoma. The combination of a uterine mass, peritoneal fluid, and a pleural effusion initially raised concern for gynecologic malignancy. The findings and outcome in our case fulfilled the definition of pseudo-Meigs’ syndrome.

Hemothorax refers to a situation wherein sufficient blood enters the pleural space to result in a pleural fluid hematocrit level that is at least 50 % that of serum. Most overtly bloody pleural effusions do not meet this criterion and are thus considered hemorrhagic but not hemothoraces; these are usually caused by pleural malignancy. In the vast majority of cases, hemothorax is caused by vascular injury, whether due to blunt or penetrating trauma, a medical procedure, or direct tumoral erosion (e.g., by metastatic sarcoma). Spontaneous (i.e., non-traumatic) hemothorax is a rare scenario in which blood accumulates in the pleural space in the absence of a discrete vascular culprit. Etiologies of spontaneous hemothorax include a miscellany of uncommon conditions such as thoracic endometriosis [ 1 ], pleural extramedullary hematopoiesis [ 2 ], or a ruptured pulmonary arteriovenous malformation [ 3 ] among many others. Although description of the coexistence of uterine leiomyoma (fibroid), ascites, and pleural effusion dates all the way back to the 1930s [ 4 ], transdiaphragmatic migration of hemoperitoneum caused by rupture of this benign uterine tumor is an exceptionally rare mechanism of spontaneous hemothorax. Herein we present what may be the first fully documented example of this unique occurrence, which fulfills the definition of pseudo-Meigs’ syndrome.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.