A Case Report of HIV-Related Bilateral Inammatory Myobroblastic Tumors of Adrenal Gland

Inammatory myobroblastic tumor (IMT) is a rare disease which mostly occurs at younger age and locates in lung in general population. We report a rare case of 44-year-old man diagnosed adrenal IMT with HIV infection, who refused regular highly active antiretroviral therapy (HAART) 13 years ago until in hospital because of ndings of adrenal masses. The patient underwent CT-guided needle biopsy successfully, and the pathological analysis documented the diagnosis of IMT by the feature of proliferation of broblastic-myobroblastic with inammatory inltration. We failed to perform tumor complete resection due to diffuse invasion of tumor under laparoscope. The patient was complicated with severely multiple pulmonary infection post to surgery because of immunodeciency, that eventually caused the death of patient 2 months later. This case reminds us that IMTs may be too aggressive and progressed in HIV-positive patients with irregular HAART to perform surgical resections, and severe immunodeciency can be more fatal. To our knowledge, this case is the second IMT patient with HIV infection worldwide, but the rst case occurs at adrenal gland rather than lung in adult.


Introduction
In ammatory myo broblastic tumor (IMT) which originates from mesenchymal tissue is a very rare disease worldwide. IMT mostly occurs at younger age and locates in lung in general population, while other rare sites are gradually reported in reccent years such as liver, pancreas, pharynx, spinal canal, retroperitoneal space and so on [1,2,3,4]. Nowadays we are used to thinking of IMT as a low-grade malignant tumor with pathological feature of proliferation of broblastic-myo broblastic cells with in ammatory in ltration and a potential of local recurrence but a lower risk of distant metastases [5].
Human immunode ciency virus (HIV) attacks body's dendritic cells and macrophages, causing de cits in T-cell function, and leading to the occurance of acquired immune de ciency syndrome (AIDS)-de ning cancers such as Kaposi's sarcoma, non-Hodgkin lymphoma [NHL], and invasive cervical carcinoma [6]. While an increased incidence of non-AIDS-de ning cancers is gradually noted along with improved life expectancy because of the advent of highly active antiretroviral therapy (HAART) worldwide [7]. IMT is one kind of non-AIDS-de ning cancers reported only one case in Romania which located in lung and occurred at younger age [8]. We present a rare case of HIV-related IMT which is the second case in the world, but the rst case occurs at adrenal gland rather than lung at middle age.

Case Report
A 44-year-old man presented with a 3-week history of a persistently dull back pain. The patient refused to accept highly active antiretroviral therapy (HAART) post to the diagnosis of HIV infection 13 years ago. On physical examination, the tapping pain at costalspinal angle was present. The extremely decreased CD4 + T-lymphocyte cell count (6 cells/µL) and really increased HIV load (10001391 copies/mL) represented collapsed immunal system, however laboratory examination showed no evidence of opportunistic infection such as Cytomegalovirus, Epstein-Barr virus, fungus, and tubercle bacilli.
Functional adrenal analysis was found to be within normal range. Abdominal unenhanced computed tomographic (CT) scan showed two hypodense and heterogeneous solid lesions adjaent to bilateral adrenal gland subsequently, and the lesion adjacent to left adrenal gland measured approximately 67mm by 38mm in size versus 56mm by 58mm of the lesion adjacent to right adrenal gland (Fig. 1A).
Meanwhile enhanced CT showed moderate and heterogeneous enhancement (Fig. 1B), following enlargement of lymph nodes in retroperitoneal space, and accompanied by an inability to recognize normally anatomical structures of adrenal gland because of tumor opression ( Fig. 2A-B). We rstly considered the diagnosis of lymphoma in light of image features and severe immunode ciency caused by HIV, subsequently a CT-guided biopsy of the lesion adjacent to right adrenal gland was proceed.
The pathological analysis of biopsy specimen documented the diagnosis of IMT.The specimen measured 4/8/12 mm in size,1mm in diameter,with a gray-white surface grossly. Histological ndings revealed a proliferation of spindle cells without obvious atypia and small vessels in myxoid and collagenous background with an in ltration of plasma cells, lymphocytes and neutrophils. Collagenous sclerosis and myxoid degeneration were seen in partial area. The spindle cells didn't exhibit nuclear pleomorphism ( Fig. 4A-B). Immunohistochemical staining con rmed that these spindle cells were diffusely and strongly positive for Vimentin (Fig. 4C), while focally and weakly positive for smooth muscle actin(SMA) (Fig. 4D).
We used emtricitabine, tenofovir, and dolutegravir to control HIV infection. After the HAART duration of 1 month, CD4 + T-lymphocyte cell count increased to 33 cells/µL, however patient's symptom of back pain became progressively worse. Acknowledging the uncertain e cacy and adverse effects of chemotherapy, steroid therapy and radiotherapy when refered to HIV infection, we selected tumor resection of bilateral lesions under laparoscope by step. Unexpectedly we failed to make it due to unde ned margine and extensive invasion of the tumor found in operation. During postoperative course the patient was complicated with multiple pulmonary infections (Fig. 4), leading to the impossibility of adjuvent therapy.The patient died of multiple organ dysfunction syndrome caused by pulmonary infection two months later ultimately.

Discussion
The most common site of IMT is lung according to former studies,while adrenal gland is unusual anatomical location [9].The patient merely presented with back pain accompanied by no other manifestations such as fever, palpable mass, and emaciation. In addition, CT showed bilateral masses with no speci cally enhanced images. Above all, the patient had a 13-year history of HIV-infection with no treatments, leading to collapsed immunal system. In light of the above aspects, AIDS-de ning cancers were given priority in differential diagnosis such as lymphoma and Kaposi's sarcoma. CT-guided biopsy of the lesion was necessary to make a diagnosis.
Pathological analysis documented a proliferation of spindle cells and an in ltration of plasma cells, lymphocytes and neutrophils in accordance with features reported in former studies [10,11]. Immunohistochemical study showed that ALK1 was negative, representing less aggressive pathology and less likely to recur [12]. A study involved 84 cases suggested a 25% increasement of recurrence rate for ALK1-positive IMT specimens versus those of ALK1 negative [13]. However intraoperative ndings showed more aggressive pathological features in our case, which was in inconsistent with the predictive effect of ALK. This contradiction might be caused by HIV infection.
Completely surgical resection is the main treatment for most IMTs, and mass biopsy should be recommended to avoid organ resection for certain patients, when it is di cult to differentiate from primary organ malignancy. A retrospective study including 22 IMTs of urinary system documented good outcomes with no recurrence or metastases in a median follow-up duration of 6.1 years, who were treated with completely mass resection or radical organ resection [14]. If incomplete resection occurs, adjuvant therapy including steroid therapy, antibiotics, radiotherapy, chemotherapy or carbon dioxide laser should be attempted. Recent study showed that ALK inhibitors appeared to be bene cial to IMT as adjuvent therapy,which had been approved e cacy for ALK-positive non-small cell lung cancer [15]. In a multicenter prospective study, 12 patients of IMTS achieved an objective response of 50%, who accepted adjuvent therapy of ALK inhibitor (crizotinib), and ALK inhibitor regarded as a kind of targeted therapy seemed to be quitely effective in treating IMTs with incomplete resection [16]. We did not succeed in mass resection because of unde ned margine and extensive invasion of the tumor in this case, that might be caused by immunode ciency.We did not recommend any adjuvent therapies as well, because the patient was complicated with uncontrolled pulmonary infection that might be caused by endotracheal intubation in operation.
IMT was used to considering as benign tumor since it was rstly reported in lung in 1939 [17]. Most of IMTs had good outcomes according to the former studies, that relied on many factors such as demographics, comorbidities, oncologic features, expression of ALK, and degree of surgical completion [4,14]. Nowadays, pathologists demonstrate IMT's aggressive features of pathology in certain cases, suggesting its malignant potential [18,19]. Neverthless, the outcome of IMT is uncertain when it comes to HIV infection due to rare case reports of HIV-related IMTs. As far as we know, only 1 case had previously been reported in Romania, who didn't undergo surgical resection but received broad-spectrum antibiotics, antiviral and antifungal treatment, and the case had good evolution without any recurrence during 3-year follow-up. In our case, the patient nally died of AIDS complications post to unsuccessful surgery withthin 2 months, that made it impossible to try adjuvent therapies and track the natural course of tumor.
Our case and Romania case were featured by collapsed immunity caused by HIV. It is reasonable to speculate that there may be a possible correlation between HIV and IMT. More studies of HIV-related IMTs are necessary to con rm that it is accidental or not.

Conclusions
The case reminds us that IMTs may be too aggressive and progressed in HIV-positive patients with irregular HAART to perform surgical resections, and severe immunode ciency can be more fatal. Whether surgical resection is appropriate for HIV-related IMT is unclear, and more studies are necessary to draw meaningful conclusions. The correlation between HIV and IMT needs to be investigated in more cases.    Pulmonary CT showed extensive in ammatory lesions of bilateral lungs