CLINICAL HIV AND AIDS JOURNAL (ISSN:2633-5476)

Neoplasms in HIV positive patients are classified as associated with AIDS and not associated with AIDS. Non-Hodking Lymphoma is found among those associated with AIDS. Burkitt lymphoma, B-celllymphoma, CNS primary Lymphoma and serous-associated Lymphoma are even more characteristic forms of presentation in this population. It is characterized by a low CD4 count and some with severe immune suppression. This case has an atypical presentation, the patient being immune suppressed under ART.

HIV; Lymphoma; Ophthalmoparesis

At the beginning of the HIV epidemic, up to 40% of people infected with HIV were expected to develop some form of neoplasm in their lives. Since the initiation of ART, these numbers have been decreasing.

Neoplasms in HIV-positive patients are classified as AIDS-associated and nonAIDS-associated. The former are characterized by being generally dependent on the immunodeficiency or related infectious agents. The most common are Kaposi’s sarcoma, non-Hodgkin’s lymphoma and uterine cancer. Non-AIDS-associated malignancies are not related to the immunodeficiency and may include anal cancer, Hodgkin lymphoma, germ cell tumor, and lung cancer [1,2].

Our goal is to communicate an unusual of a B-cell NHL in an HIV positive patient.

 A42-year-old female with HIV, diagnosed approximately 1 year ago on treatment with Raltegravir 400 mg/day, Emtricitabine and Tenofovir 300/300 g/day with good adherence to treatment and good immune status (Viral Load: 20 copies and CD4 378/mm³ was admitted to ICU for severe headache (10/10 according to pain VAS) and ophthalmo paresis (paralysis of de III right cranial nerve). She had been hospitalized in another center for low back pain attributed to lumbar disc pathology. A nerve root block was performed with poor response. An MRI of the spine showed an expansive formation at the rectum-anal level that infiltrates the sacrum and bone marrow. A biopsy sample was taken by colonoscopy and she was discharged with pain treatment: NSAIDs and opioids.

Upon admission to the ICU of our hospital, an MRI was performed with angio resonance of intra and extra cranial vessels. The study showed a small image in the posterior region of the right cerebellar hemisphere compatible with ischemic sequel; 5 mm acoustic schwannoma inside the left internal auditory canal and a doubtful aneurysmal image in the left internal carotid artery. The patient underwent a digital angiography that ruled out aneurysmal pathology and vascular malformations.

A first lumbar puncture (LP) was also performed with elevated CSF protein concentrations (0.98 g/L) and without cellular elements. Direct examination and cerebrospinal fluid cultures were negative. She was transferred to the Internal Medicine Service to complete her study and treatment.

Vital Signs: BP 120/80 mmHg - HR 87/min – RR 19/min – BT <37.8 ºC – O₂ Sat 98%.

Cardiovascular: no alterations

Respiratory: no alterations

Abdomen: no alterations

Neurological: lucid. Dysphonia and dysphagia with runny nose during swallowing. Normal mobility of the palatal veil with gagging and cough reflexes present. Complete paralysis of the III right cranial nerve. Left predominant paraparesis with preserved osteotendinous reflexes and indifferent plantar reflex. No sensitive level but with acute retention of urine, interpreted as secondary to root compression.

Blood analysis 

A second lumbar puncture was performed and showed and clear CSF with pleocytosis> 200 cells (60% PMN). Proteins and glucose was normal (Table1).

The PCR tests on cerebrospinal fluid for JC – Mycobacterium tuberculosis – CMV – EBV were negative as well as staining with Chinese ink for Cryptococcus. The cultures of cerebrospinal fluid were negative too.

The approach of this patient is complex and therefore we must first begin with an anatomical discussion. Tumors of the sacrum region with root compromise on one side and alterations of the cranial nerves by a tumor at the skull base on the other side. We could think of a solid tumor with metastases, but a high-grade B-cell lymphoma with neurological compromise was most likely. ACD4 <200 cell/mm recount value is a pro for B lymphoma however the patient has a count of 378 cells and being under ART is presumed to have a long-standing infection which favors the oncological process. Negative serology for EBV does not rule it out because it is not a primary tumor of the nervous system but it infiltrates the meninges, it is also rare but may have started in recto [3].

It has been estimated that the incidence of NHL in patients with HIV infection is over 100 times that found in the general population [4] and in cases of HL it is between 5 and 15 times the rate of the general population [5]. In patients with HIV infection, diffuse large cell lymphoma B strain (LDCGB) and Burkitt lymphoma (BL) are the most common forms of NHL. In the case of HL, histological variants of mixed cellularity and lymphocyte depletion are the most common. Certain types of lymphoma occur specifically in HIV-infected patients, such as primary effusion lymphoma (PEL) and plasmoblastic lymphoma. In patients with HIV infection, the occurrence of diffuse large cell lymphoma (LDCG) in the central nervous system (CNS) as well as primary CNS lymphoma occurs more frequently [6].

Another diagnosis to be considered is meningeal carcinomatosis associated with non-Hodgkin’s lymphoma as it is the second most common neoplasm in AIDS patients. On the negative side, the isolated impact of the CN III is not a common occurrence. Compared to lymphomas in the HIV negative population, lymphomas in HIV patients are more likely to present advanced-stage disease, extranodal compromise, or atypical location. The absence of tumor cells in CSF does not exclude this diagnosis, since the sensitivity does not exceed 46% when compared to what was found in the necropsies of deceased patients with meningeal carcinomatosis [7-10].

As a non-tumoral cause we must think in this case of LambertEaton Myasthenic Syndrome (LEMS), as it is found in the list of differential diagnoses of any pathology with ocular involvement. It can be presented at any age range, mainly in females.

Myasthenia gravis was also considered as it may be a para neoplasticthymoma phenomenon but it has also been associated with extrathymic tumors such as small cell lung cancer and Hokdking lymphoma. However, the pure ocular form is uncommon and, in addition, both the ACRA (antibodies against the acetylcholine receptor) and the anti-MUSK antibodies and an EMG with repetitive stimulation were normal [11,12].

The diagnosis was confirmed by biopsy of the rectal mucosa with stromal infiltrate composed of elements of spherical nucleus and very scarce cytoplasm. There is some degree of attrition, they show moderate nuclear atypias, sometimes clear nucleus and prominence nucleus: Ck: (-), SYN: (-), VIM: very mild positivity, CD20: + weak, granular, CD3: (-), CD99: weak, GFAP: (-). The histological image, in the clinical context of the patient, may be linked to a lympho proliferative lesion, probably of the B. strain linked to its underlying disease and immune suppression.

The presentation of lymphoma in this patient was atypical, however it is an etiology to always consider in patients with serology positive for HIV with CD4 count below 200 cells.

The authors declare no conflict of interest.

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