Department of Pathology, Dr Babasaheb Ambedkar Road, Mumbai 400022 India;

Two benign liver lesions with little malignant potential are nodular regenerative hyperplasia and hepatocellular adenoma. It appears that nodular regenerative hyperplasia is an adaptive response to hepatic vasculopathy. The usage of anabolic steroids, oestrogen, metabolic disorders, and vascular abnormalities are all linked to hepatocellular adenoma. We describe an interesting case of a young woman who arrived with edoema, coughing, and increasing dyspnea. Within two days of her stay in the hospital, she passed away from her sickness. A medical autopsy revealed pulmonary hypertension, intrapulmonary haemorrhage, and hepatocellular adenoma developing against the backdrop of nodular regenerative hyperplasia

Keywords:Hepatic adenomas, nodular regenerative hyperplasia, and hepatic vascular disease,

Hepatocellular adenoma (HCA) and nodular regenerative nodule (NRH) are uncommon benign liver abnormalities. Regenerating hepatic nodules without fibrous septa and atrophy of the parenchyma in between are characteristics of NRH. It is a hepatocytes' adaptive response to portal obliterative venopathy [1]. HCA is an uncommon benign hepatic tumour that is frequently linked to the use of anabolic steroids, oestrogen, metabolic illness, and in rare cases, vascular abnormalities [2]. Rare case reports of NRH and HCA occurring simultaneously have been found in the literature [3,4]. In this article, we describe an unique NRH and HCA combination in a young female who passed away from pulmonary hypertension (PH) and intrapulmonary haemorrhage.

A 21-year-old single woman was admitted to the hospital with a cough and dyspnea that worsened over the course of 10 days, progressing from grade 1 to 4. Multiple episodes of widespread oedema and vomiting were followed by unconsciousness. Her past medical history included a negative pregnancy test and three years of amenorrhea. Hyperprolactinemia was identified in the patient. The level of serum prolactin was 280ng/ml. Primolut N and Cabergoline (0.5mg) tablets were used to treat her (10 mg). There was no prior history of endocrine, cardiac, or connective tissue disorders. Routine laboratory tests were conducted at the time of admission and were within normal bounds. Total bilirubin was 2.4 mg/dl, AST was 218 IU/ml, and ALT was 111 IU/ml for serum creatinine.

Severe pulmonary artery hypertension was detected by 2D echo. Due to intrapulmonary haemorrhage and pulmonary hypertension, the patient passed away two days after entering the hospital. There was a medical autopsy done. Volumetric and hemorrhagic lungs were discovered during a systemic evaluation. Atherosclerotic plaque was visible in the main pulmonary artery. There was no sign of hyperplasia or adenoma in the pituitary gland, which was normal. There were no oesophageal varices or splenomegaly. A gross examination of the liver revealed several small yellowish-white nodules with diameters between 0.2 and 0.5 cm. A single massive, well-defined, tan-gray nodule measuring 2x1x1cm . Noncirrhotic liver parenchyma was present nearby. Necrosis, haemorrhage, or a central scar were not present. The rest of the organs were ordinary. Diffuse little nodules with histopathology evidence of NRH, showing regenerating hepatocytes creating nodules without fibrous septa. Hepatocytes around nodules exhibited atrophy. On microscopic analysis of a single big nodule, hepatocytes were grouped in three to four cell thick trabeculae with bland morphology and no atypia or elevated nuclear to cytoplasmic ratio. The lesion was also partially encapsulated. (See Figure 2B.) The lesion had a few unpaired arteries but no interlobular bile ducts, which suggested HCA. There was no macrovesicular steatosis or inflammation. Thick trabeculae were seen in reticulin stain without reticulin network degradation. To rule out hepatocellular cancer, glypican 3 and CD34 immunohistochemistry (IHC) were performed. 2% was the Ki67 mitotic index.

Most benign liver nodules are asymptomatic and are only discovered by accident or during an autopsy. Small regenerating nodules occur in the liver parenchyma in NRH, which can evolve to non-cirrhotic portal hypertension. The gold standard for NRH diagnosis continues to be histopathology. There is still no consensus regarding the pathogenesis of NRH. According to several views, the cause of the condition could be autoimmune, haematological, infectious, neoplastic, or drug-induced [1]. According to studies, pharmaceuticals like steroids, anticancer medications, immunosuppressants, and birth control pills play a role in the development of NRH. The phenomena of portal obliterative venopathy, which causes nodular transformation of the liver (NRH), has been described by Wanless et al [1]. 107 liver samples from NRH patients showed destroyed portal venules, according to Nakanuma et al. [5].

On a 2D echo, the patient's respiratory symptoms were identified as pulmonary arterial hypertension. Lung histopathology revealed PH characteristics and a sizable thrombus. At the autopsy, NRH was a coincidental finding. Rarely do NRH and PH coexist. Two autopsy cases of NRH connected to PH were reported by Yutani et colleagues in 1988 [6]. Multifocal nodular hyperplasia of the liver with noncirrhotic portal hypertension was described by Portmann B et al in one case, which was further worsened by PH [7]. They have clarified that nodular lesions in the liver may have been caused by prolonged exposure to blood-born hepatotropic agents. Three cases of NRH with connective tissue disease were described by Watabe H et colleagues in 2006 [8]. In the course of each patient's condition, PH and then NRH were both developed.

Liver histology also revealed the presence of HCA in addition to NRH. It is unknown at what point both hepatic nodules first emerged. There are very few isolated case reports of NRH and HCA coexisting in the literature [3,4]. HCA has been linked to the use of anabolic steroids, oestrogen, metabolic diseases, and in rare cases vascular abnormalities in women of childbearing age [2]. This patient was prescribed Primolut, which contains norethisterone, after being found to have hyperprolactinemia.

This could be one of the HCA's causal agents. The precise length of the treatment, however, was unknown. Between NRH and HCA, hepatic vascular pathology may be a common denominator. Hepatic vascular pathology has been linked to benign hepatic nodular lesions, according to Sempoux C et al [9]. In addition to congenital and acquired hepatic hemodynamic anomalies, Kobayashi S et al explored the radiological and histological features of hepatocellular nodular lesions in conjunction with [10]. Recently in 2020 Bell P D et al found HCA developing in patients with systemic lupus erythematosus on the back of NRH [4].

They have suggested that the hepatic vasculopathy linked to SLE, a systemic inflammatory disease, may be responsible for both nodular lesions. Our instance demonstrates an odd connection between PH, NRH, and HCA. The pathogenesis may be complex or it may be a coincidence between pulmonary hypertension and hepatic nodules. All three lesions may share a common aetiology called vascular pathology. While pulmonary veno-occlusive disease and thromboembolic phenomena were major complications of PH, the modification in hepatic microvasculature that resulted in NRH and HCA seems to have been a side effect.

We describe a highly uncommon instance of NRH and HA related to PH. In this situation, vascular pathology may be a common occurrence for all three lesions. Therefore, it is advisable to use imaging techniques to rule out related disorders in PH patients.

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Anjali D Amarapurkar. Two benign hepatic nodules with pulmonary hypertension: A Case Report. International Journal of Gastroenterology and Hepatology 2022.