Isolated Hepatic Hemangiomatosis Leading to Fatal Consumptive Coagulopathy in an Elderly Patient: A Case Report

Abstract

Patient: Male, 74-year-old

Final Diagnosis: Isolated hepatic hemangiomatosis

Symptoms: Anemia • coagulopathy • liver failure • thrombocytopenia

Clinical Procedure: —

Specialty: Gastroenterology and Hepatology

Objective: Unknown etiology

Background

The most common vascular lesions of the liver are hepatic hemangiomas (HH), which are generally asymptomatic and do not require medical intervention. However, when the lesions are large or multiple, they can be a significant clinical problem. This report describes a unique case of an elderly patient with isolated hepatic hemangiomatosis associated with the onset of consumptive coagulopathy and hemolytic anemia, ultimately resulting in liver failure and death.

Case Report

A 74-year-old man presented with jaundice, progressive weight loss, fatigue, lower-limb edema, and recurrent epistaxis. Laboratory findings revealed normocytic anemia, thrombocytopenia, hyperbilirubinemia, hypoalbuminemia, and elevated liver enzymes. Abdominal ultrasound (US) and computed tomography (CT) demonstrated hepatomegaly with multiple hypoechoic and hypodense focal lesions, initially raising suspicion of metastatic disease. Colonoscopy and upper gastrointestinal endoscopy showed no evidence of malignancy. A core-needle biopsy of the hepatic lesions, complemented by positron emission tomography–computed tomography (PET-CT) and magnetic resonance imaging (MRI), confirmed the benign nature of the lesions, consistent with isolated hepatic hemangiomatosis.

The patient was managed symptomatically and discharged home with recommendations for continued outpatient monitoring and urgent consultation in the event of any clinical deterioration. Unfortunately, after 3 months of relative symptoms improvement, he developed gastrointestinal bleeding and acute liver failure, which ultimately resulted in his death.

Conclusions

Hepatic vascular lesions are diagnostically challenging; definitive diagnosis requires correlation of clinical, imaging, and histopathological findings, as well as multidisciplinary consultation. The clinical course of hepatic hemangiomatosis ranges from benign to life-threatening, with potential complications such as hepatic failure or coagulopathy.

Introduction

Vascular lesions of the liver are a heterogeneous group of pathologies, ranging from benign and asymptomatic, to moderately aggressive lesions that cause localized tissue destruction, and ultimately to highly invasive malignancies that actively metastasize and rapidly destroy hepatic parenchyma along with adjacent structures [1]. Accurate differentiation among these lesions is clinically important, as misdiagnosis can lead to delayed or inappropriate management. Distinguishing between these lesions requires a multifaceted diagnostic approach including various imaging techniques such as US, CT, MRI, and PET-CT. When imaging findings are inconclusive, histopathological examination plays a crucial role in establishing a definitive diagnosis and in most cases allows for the selection of appropriate treatment [1].

Hepatic hemangiomatosis is a rare disorder characterized by multiple, poorly demarcated vascular lesions resembling cavernous hemangiomas, which infiltrate and replace healthy liver parenchyma [1,2]. While predominantly described in pediatric populations, isolated adult cases are exceedingly rare, with fewer than 20 reported in the literature [3]. This condition often remains asymptomatic for extended periods of time, but it can also lead to the development of life-threatening complications resulting from the functional loss of the liver parenchyma and impaired perfusion of the affected organ [2,3]. A particularly dangerous and extremely rare complication of hepatic vascular lesions is the Kasabach-Merritt phenomenon (KMP) – a coagulation disorder, manifested by thrombocytopenia, disseminated intravascular coagulation, and hemolytic anemia. This syndrome primarily affects neonates and infants and is typically associated with the presence of large Kaposiform hemangioendothelioma (KHE) or tufted angioma (TA) [4,5].

In this report, we present the case of an elderly man with isolated hepatic hemangiomatosis complicated by hemolytic anemia, thrombocytopenia, and consumptive coagulopathy, leading to progressive liver failure and death.

Case Report

A 74-years old man with a history of hypertension, chronic venous insufficiency, and epilepsy was admitted to a local internal medicine department after experiencing progressive jaundice and weight loss (approximately 10 kg) over the previous 5 months. He reported weakness, lack of appetite, swelling of both lower limbs, and a sensation of distention in the right upper quadrant of the abdomen. He also had chronic constipation and recurrent epistaxis, which required frequent medical management, beginning a few months prior to admission. His long-term medication regimen included telmisartan (20 mg once daily), alprazolam (2.5 mg once daily), and valproic acid (300 mg twice daily). He denied previous alcohol abuse, recreational drug use, exposure to metoclopramide, use of steroids, or relevant exposure to any known environmental toxicants.

The initial abdominal US revealed a moderately enlarged liver (craniocaudal dimension 193 mm) with an irregular surface, heterogeneous echostructure, and multiple hypoechoic and hyperechoic focal lesions showing minimal or absent Doppler flow. The largest lesion (35 mm in diameter) was located at the hepatic hilum (Figure 1). These findings raised suspicion for multiple liver metastases. To identify a potential primary tumor and to detect the presence of any neoplastic lesions in other parts of the body, a contrast-enhanced CT of the chest, abdomen, and pelvis was performed. The CT showed a mild thickening of the proximal part of the transverse colon at the hepatic flexure and numerous, mainly hypodense, hepatic lesions, suggesting multiple liver metastases accompanied by capsular retraction (Figure 2). No ascites or enlarged lymph nodes were detected. Moreover, the scan revealed a small, solitary solid nodule in segment 6 of the left lung, subtle bilateral fibrous lesions near the diaphragm, and multiple minor thyroid nodules with benign appearance in subsequent US (EU-TIRADS 2). Given the suspicion of metastatic transverse colon cancer, the patient underwent colonoscopy, which showed no pathological findings except for small hemorrhoids. Upper gastrointestinal endoscopy revealed mild bile reflux gastropathy without any other abnormalities or suspicious lesions. Due to the absence of a detectable primary tumor, he was referred to the surgical oncology department for a targeted core-needle biopsy of the liver.

Figure 1.

Abdominal ultrasound showing the sonographic image of the liver. Notable features include the heterogeneous parenchyma of the organ and the presence of numerous oval focal lesions with varying echogenicity. The largest, hyperechoic lesion with hypoechoic halo was located near the hepatic hilum.

Figure 2.

Contrast-enhanced computed tomography. The study shows multiple irregular lesions occupying almost the entire liver, which progressively fill with contrast. (A) axial view, before contrast administration; (B) axial view, arterial phase; (C) axial view, venous phase; (D) axial view, 10 minutes delayed phase; (E) coronal view, arterial phase; (F) coronal view, venous phase.

One month later, after appropriate preparation, an ultrasound-guided core-needle biopsy was performed, obtaining 3 samples from separate hepatic lesions. There were no signs of bleeding after the procedure, so the patient was discharged home with a recommendation to attend a follow-up visit after obtaining the histopathology results. While awaiting the biopsy results, a whole-body PET-CT scan with fluorodeoxyglucose was performed, showing no pathological increase in radiotracer uptake (Figure 3). Histopathological examination revealed fragments of normal liver parenchyma infiltrated by a benign, hemangioma-type vascular tumor composed predominantly of dilated vascular channels of varying wall thickness, lined by a single layer of flat, CD34-positive endothelial cells without cytological atypia (Figure 4). No metastatic or cancerous cells were detected. Due to the absence of confirmed neoplastic disease, the surgical oncology department referred the patient to the gastroenterology department for further evaluation.

Figure 3.

Positron emission tomography-computed tomography (PET-CT). The study did not demonstrate pathological uptake of the radiotracer. (A) non-contrast computed tomography (CT). (B) PET-CT image.

Figure 4.

Microscopic characteristics of hepatic hemangiomatosis using hematoxylin-eosin and CD34 immunostaining. (A) Low-magnification view showing shreds of normal liver parenchyma infiltrated with fragments of a hemangioma-type vascular tumor containing erythrocyte-filled, various-sized, vascular channels separated by fibrous septa (hematoxylin-eosin; 100×). (B) Higher-magnification view of the boxed area in panel A showing narrow (solid arrows), and extensively dilated (open arrows) pathological vascular spaces filled with erythrocytes and lined by flattened endothelium. The vascular lumina are separated by fibrous stroma forming septa of variable thickness (hematoxylin-eosin; 200×). (C) Dilated vascular spaces are lined by CD34-positive endothelial cells (immunoperoxidase; 200×). (D) Higher magnification of the boxed area in panel C demonstrating the delicate single-layer flat endothelial cells without any signs of cytological atypia (immunoperoxidase; 400×)

Upon admission to the gastroenterology department, physical examination revealed malnutrition, jaundice, mild lower-extremities edema, and minor purpuric lesions on the distal parts of extremities. No mucocutaneous telangiectasias were observed on the lips, oral mucosa, or surrounding skin. The liver was enlarged and firm on palpation, extending slightly below the right costal margin. Laboratory tests showed moderate normocytic anemia (8.9 g/dL [13.7–17.5 g/dL]) with lowered haptoglobin concentration (19 mg/dL [30–200 mg/dL]), thrombocytopenia (62×10³/μL [163–337×10³/μL]), impaired coagulation (INR 1.6 [0.8–1.2], APTT 48.7 s [25.1–37.7 s]), hyperbilirubinemia (total bilirubin 5.14 mg/dL [<1.2 mg/dL]) with predominance of conjugated bilirubin (2.95 mg/dL [<0.3 mg/dL]), increased levels of ammonium (132.7 g/dL [27.2–102 g/dL]), elevated levels of hepatic transaminases (ALT 45 U/L [<41 U/L], AST 52 U/L [<40 U/L]), GGTP (1007 U/L [<60 U/L]), ALP (158U/L [40–130 U/L]), and d-dimer (>34 000 ng/mL [age-adjusted reference level <750 ng/mL]). Active or previous HBV, HCV, or HAV infection were excluded, and tumor markers (CEA, CA19-9, and AFP) were within the normal limits, supporting a non-malignant vascular etiology. Contrast-enhanced MRI of the abdomen revealed numerous, hepatic focal lesions occupying almost the entire organ. The lesions were hyperintense on T2-weighted images and hypointense on T1-weighted images, with imaging characteristics suggestive of hepatic cavernous hemangiomas. Most lesions exhibited progressive centripetal contrast enhancement, with incomplete filling observed in the largest ones (Figure 5). No pathological calcifications or foci of necrosis were observed. The previously described thickening of the transverse colon was not visualized on MRI. Magnetic resonance cholangiopancreatography (MRCP) did not reveal any modelling or dilatation of the biliary tract.

Figure 5.

Contrast-enhanced magnetic resonance imaging of the abdominal cavity showed an enlarged liver with polycyclic contours and uncountable, different-sized focal lesions occupying almost the entire organ. Most of the lesions progressively fill with contrast in a centripetal manner. The largest lesions exhibit incomplete, nodular or irregular contrast filling. (A) T2-weighted images. (B) T1-weighted images. (C) arterial phase. (D) venous phase. (E) portal phase. (F) 10-minute delayed phase.

All imaging studies were reviewed by a radiology specialist, who found no evidence of progression over time. No extrahepatic vascular abnormalities were identified. The differential diagnosis included hepatic hemangiomatosis (HHS), hepatic epithelioid hemangioendothelioma (HEHE), hereditary hemorrhagic telangiectasia (HHT), and systemic hemangiomatosis. Based on sequential CT, MRI, and PET-CT findings, it was concluded that the radiological appearance of the hepatic lesions was most consistent with isolated hepatic hemangiomatosis. The patient was also re-evaluated by oncologists and surgical oncology specialists, who ruled out malignancy and recommended further follow-up under gastroenterological supervision.

Alprazolam and valproic acid were discontinued. The patient was started on ursodeoxycholic acid (500 mg twice daily), spironolactone (25 mg once daily), lactulose (7.5 g twice daily), and ornithine citrate (3 g once daily), obtaining incomplete but significant subjective symptom improvement. Following a discussion of the available therapeutic options and in alignment with the patient’s preferences, he was discharged with recommendations to avoid hepatotoxic factors, maintain a high-protein diet, continue outpatient monitoring, and seek urgent medical consultation in the event of clinical deterioration.

After 3 months of relative mitigation of symptoms, the patient was admitted to a local hospital due to severe gastrointestinal bleeding and hepatic function decompensation, manifesting as coagulopathy, worsening jaundice, and severe encephalopathy. Despite intensive medical management and blood component transfusions, he died soon after admission. Personal, non-medical considerations precluded postmortem examination.

Discussion

This case underscores that accurate diagnosis of hepatic vascular lesions can be inherently challenging and requires clinical correlation, integration of multimodal imaging, and histopathological confirmation. Furthermore, it illustrates that isolated hepatic hemangiomatosis, although rare, should be considered in the differential diagnosis, as it may be complicated by serious conditions such as consumptive coagulopathy, potentially resulting in rapid clinical deterioration.

Our patient’s symptoms can be partially attributed to the presence of multiple lesions exerting pressure on hepatocytes and small bile ducts. Given the multiplicity and large size of some vascular lesions, we hypothesize that the patient’s symptoms (frequent, difficult-to-control epistaxis, and petechiae on the distal parts of the limbs) along with the associated laboratory abnormalities (thrombocytopenia, abnormal INR, and APTT, anemia with low haptoglobin levels, and hyperbilirubinemia) can be explained by chronic intravascular coagulation within these lesions and secondary hemorrhagic coagulopathy resulting from the depletion of platelets and coagulation factors.

This constellation of findings (thrombocytopenia, angiopathic hemolytic anemia, and consumptive coagulopathy) in the presence of a rapidly growing vascular tumor is characteristic of KMP, a rare disorder predominantly observed in neonates and infants [4,5]. KMP arises from turbulent blood flow through tortuous vascular channels, leading to platelet aggregation and activation of coagulation pathways on damaged vascular endothelium, while hemolytic anemia results from mechanical destruction of erythrocytes by the walls of the vascular lesions and platelet aggregate [5,6]. The diagnosis of KMP is primarily clinical but can be supported by imaging studies (CT, MRI) and laboratory findings, although biopsy is often omitted due to the high risk of bleeding [5–7]. KMP is most associated with a single, large, painful, and rapidly growing vascular lesion, usually located in the skin or adjacent soft tissues. Deep-seated vascular lesions without cutaneous involvement account for a minority of cases and carry a worse prognosis [5].

Despite Kasabach and Merritt’s original 1940 description of a boy with the classic triad of KMP symptoms and a vascular lesion referred to as a “giant capillary hemangioma,” some authors suggest that KMP is exclusively associated with 2 types of vascular tumors – KHE and TA – which have distinctive imaging findings and histopathological characteristics [1,5,6,8]. While KHE and TA are extremely rare in adults, isolated cases of these tumors causing KMP-like manifestations have been documented [9,10]. A review of the English-language literature did not identify any cases of KHE or TA occurring exclusively in the liver, further underscoring the uniqueness of our observation. Additionally, a few case reports describe instances where the classic KMP triad was triggered by other vascular liver lesions, including angiosarcoma, HEHE, giant cavernous hemangiomas, and hepatic hemangiomatosis [2,11–13].

Hepatic hemangiomatosis is a rare condition characterized by poorly demarcated vascular lesions in the liver, which replace a significant portion of the normal hepatic parenchyma [14]. Histopathological examination reveals vascular spaces of varying sizes lined by a single layer of flat epithelium without cellular atypia. Hemangiomatosis is more common in women than in men, and is usually associated with a giant hemangioma (diameter greater than 4 cm) [14]. Typical imaging findings include heterogeneous, poorly-defined vascular lesions that appear hypoattenuating on non-contrast CT, hypointense on T1-weighted MRI, and hyperintense on T2-weighted MRI, with progressive enhancement in the late dynamic phases of contrast studies [2,13,15,16]. Hepatic hemangiomatosis can be completely asymptomatic [17], manifest as pain or discomfort in the right upper quadrant [18], or present with severe complications, including disseminated intravascular coagulation (DIC), heart failure, or liver failure [13,16]. It can be part of the clinical spectrum of certain syndromes, such as hereditary hemorrhagic telangiectasia (HHT, previously known as Rendu-Osler-Weber syndrome) or systemic hemangiomatosis [3]. However, in our case, no vascular lesions were identified elsewhere in the body, nor were there telangiectasias of the mucosa or gastrointestinal tract, which excludes the presence of these syndromes.

Although most cases of hepatic hemangiomatosis occur in neonates and infants, isolated adult cases have been reported, with only about 20 documented worldwide [2,3]. Some of these were associated with KMP-like manifestations. For instance, Eun et al reported a case of a 33-year-old woman with histologically confirmed isolated hepatic hemangiomatosis and nearly identical imaging findings. She developed symptomatic anemia, thrombocytopenia, and acute liver failure, which ultimately led to her death [16]. Conversely, Maeda et al described a 47-year-old woman with hepatic hemangiomatosis complicated by Budd-Chiari syndrome, who achieved complete remission following liver transplantation [3].

The vascular lesions observed in hepatic hemangiomatosis, both histologically and on imaging studies, most closely resemble cavernous hemangiomas, which are typically congenital, asymptomatic vascular lesions of the liver, often discovered incidentally. On ultrasound, these lesions are usually well-demarcated, oval, and hyperechoic (less commonly hypoechoic with a hyperechoic rim), while larger lesions may appear as heterogeneous focal abnormalities exhibiting minimal or no detectable blood flow on Doppler imaging [15]. On non-contrast CT, they appear hypoattenuating, whereas in MRI, they are hypointense on T1-weighted images and hyperintense on T2-weighted images. After contrast administration, HH typically demonstrates peripheral nodular enhancement in the arterial phase, followed by progressive, homogeneous, and usually complete centripetal filling in the venous and delayed phases [15]. While rare cases exist where hepatic hemangiomas led to life-threatening complications, multiple hepatic vascular lesions causing severe symptoms, as observed in our patient, should primarily be differentiated from HHS and HEHE. HHS, the most aggressive vascular malignancy of the liver, typically affects older men in the sixth or seventh decade of life and presents with varied growth patterns.

Extrahepatic metastases occur in approximately 20% to 40% of cases at diagnosis [1,19]. A characteristic imaging feature of HHS is intense contrast enhancement during the arterial phase, usually progressing centripetally (less commonly centrifugally or irregularly), followed by contrast washout in the delayed phase [20–22]. In contrast, the hepatic lesions in our patient exhibited slow contrast enhancement, with most achieving full enhancement only in the delayed phase – a pattern more typical of hepatic hemangiomatosis [1,2,12,15]. PET-CT may provide valuable data for differential diagnosis, as HHS typically demonstrates intense 18-FDG uptake [23], but cases of HHS with low radiotracer uptake on PET-CT have also been described, further complicating preoperative diagnosis [21]. Histopathologically, HHS is characterized by pleomorphic atypical cells with mitotic figures forming vascular channels. These channels exhibit a wide spectrum of patterns, ranging from excessively dilated sinusoidal spaces to slit-like, freely anastomosing vascular channels or papillary structures within the vascular lumen [24].

HEHE is a rare tumor of intermediate malignancy that most commonly affects middle-aged women, causing a wide range of nonspecific symptoms. It typically presents as multiple peripheral nodules, although it can also appear as a solitary lesion or in a diffuse pattern. Similar to HH and hepatic hemangiomatosis, HEHE is hyperintense on T2-weighted imaging and hypointense on T1-weighted imaging. In contrast-enhanced imaging, characteristic features of HEHE include its peripheral location, capsular retraction, the so-called “target sign” (a contrast enhancement pattern observed in 70% to 96% of cases, characterized by different intensities between the central and peripheral tumor areas, often persisting into the hepatobiliary phase), and the “lollipop sign” (abrupt cutoff of a brightly enhanced vessel at the border of a non-enhancing, hypointense tumor) [25]. The diagnosis of HEHE is based on histopathological examination of liver tissue obtained via core-needle biopsy. The tumor consists of irregular, spindle-like epithelioid cells, often containing multiple cytoplasmic vacuoles, which align along the hepatic sinusoids and central veins of the lobules. HEHE typically contains large amounts of centrally located stroma, as well as focal calcifications [26]. Although HEHE occasionally exhibits aggressive behavior, the imaging features in our patient were non-specific and, more importantly, the histopathological findings did not support this diagnosis. Furthermore, the pathological increase in radiotracer uptake, typically observed in HEHE on PET-CT, was not present.

As demonstrated above, diagnosing hepatic vascular lesions remains challenging due to overlapping imaging features, the potential for an atypical course, and uncharacteristic tumor appearances. Definitive diagnosis usually requires correlation of clinical presentation, epidemiological data, imaging studies, and histopathological examination. Despite extensive diagnostic workup, no signs of malignancy were found in our patient. The most likely diagnosis was hepatic hemangiomatosis complicated by hemolytic anemia, thrombocytopenia, consumptive coagulopathy, and acute liver failure. Confirmation would require histopathological examination of the entire liver after transplantation or postmortem; however, an autopsy was not performed for reasons beyond our control. This case, along with the literature review, demonstrates that the prognosis of hepatic hemangiomatosis is unpredictable – from long-term survival to rapid progression with severe complications and death [2,3,15,16,18,19]. The lack of established treatment standards is due to the rarity of the disease, although therapies such as steroids, anti-VEGF drugs, embolization, partial liver resection, and liver transplantation (LT) have been described [3,14,18]. Given the extensive vascular involvement, the severely reduced volume of functional hepatic parenchyma, and the absence of clearly dominant vascular lesions, the multidisciplinary team determined that neither partial liver resection nor TACE was likely to provide any clinical benefit in this case, and that LT was the only potentially curative treatment option. During hospitalization in the gastroenterology department, the patient was counseled regarding the available therapeutic options. Given the subjective improvement reported by the patient, the absence of radiological evidence of lesion progression or worsening coagulopathy, and following a discussion of the preferred management strategy with the patient, a decision was made to proceed with close observation. He was advised to present promptly to a tertiary referral center in the event of any deterioration in general condition. Unfortunately, the sudden deterioration of his clinical condition and hospital admission without the possibility of LT prevented timely surgery.

Conclusions

Definitive diagnosis of hepatic vascular lesions is often challenging and requires careful correlation of clinical, imaging, and histopathological findings, supported by multidisciplinary consultation. Although adult-onset isolated hepatic hemangiomatosis is extremely rare, it should be considered in the differential diagnosis of atypical vascular lesions of the liver. Given the variable clinical course, which range from asymptomatic and benign to life-threatening presentations associated with thrombocytopenia, hemolytic anemia, consumptive coagulopathy, and rapid clinical deterioration, early recognition and coordinated therapeutic approach are essential. Given the scarcity of reported cases, further collaborative research is needed to clarify the disease’s natural history, prognostic determinants, and optimal treatment strategies.