Today’s morning report case was a 62 year old M with no known PMH (15 pack year smoking history) presenting with chronic cough, shortness of breath and weight loss. Labs were significant for mild anemia/thrombocytopenia and significant lymphopenia and CXR showed a large right pleural effusion. The patient was subsequently found to be HIV+ (first diagnosis, CD4 count 52).
Differential for pleural effusions in HIV+ patients:
– Infectious etiologies: Must consider the common bacteria that cause pneumonia (Strep pneumo, Staph aureus), which accounts for up to 30% of pleural effusions in HIV patients. Mycobacteria (M Tb, MAC), PCP, cryptococcus and disseminated histoplasmosis should also be considered, especially when the CD4 is <150.
– Malignant etiologies: Kaposi Sarcoma (large bilateral pleural effusions, majority present with skin lesions), Non-hodgkin lymphoma (presents with pulmonary nodules/masses, lymphadenopathy, hepatosplenomegaly), Primary effusion lymphoma, primary lung cancer and metastases.
– Other causes of pleural effusions such as heart failure, hypoalbuminemia, nephrotic syndrome/CKD should also be considered.
Our patient received a thoracentesis demonstrating an exudative effusion with 46% “other” cells, which were identified as large lymphoma cells. Further cytology studies revealed CD19/CD20 negative, CD45 positive, HHV8 positive neoplastic cells, and the patient was diagnosed with Primary Effusion Lymphoma.
Primary Effusion Lymphoma (PEL)
– PEL is a rare HIV associated non-Hodgkin’s Lymphoma (accounts for 4% of HIV associated NHL)
– Arises in body cavities such as pleural space, pericardium and peritoneum and generally demonstrates evidence of HHV-8 infection (>90% of HIV associated PEL also are EBV+). There are usually no extracavitary tumor masses present and patients typically present with dyspnea (from pleural/pericardial disease) or abdominal distension (from peritoneal disease). Imaging typically does not show any solid masses, mediastinal enlargement or parenchymal abnormalities.
– The prognosis for PEL is poor with median survival time of ~6 months.
– The diagnosis is made by analyzing effusions (will almost always be positive for malignant cells due to the liquid-phase growth of tumor). The malignant cells are usually CD45+ but negative for most B cell markers (CD19, 20, 79a) and T cell antigens.
– There is limited data on the treatment of PEL and generally involves initiation of antiretroviral therapy, cytotoxic chemotherapy, and local radiation therapy.
Thank you Brian Yu for presenting such an interesting and rare case!
Today we presented a case of a 44 year old M with no significant past medical history who reported a 3 month history of shortness of breath and abdominal pain and distension. Given the history and physical exam findings consistent with a volume overloaded state, the initial differential diagnosis included causes of heart failure, liver disease and renal disease (ESRD, nephrotic syndrome). Labs were significant for an infiltrative pattern of liver injury (significantly elevated alkaline phosphatase, minimally elevated transaminases and normal bilirubin) as well as an elevated globulin gap of 4.8. TTE showed reduced an ejection fraction of 35% and abdominal ultrasound demonstrated cirrhosis and ascites.
Work-up of an elevated globulin gap:
– An elevated globulin gap (difference between the total serum protein and serum albumin concentration) should always be evaluated. The first step in evaluation is to determine whether it represents a monoclonal or polyclonal gammopathy.
– Causes of polyclonal gammopathy include viral infections (acute HIV, hepatitis C), connective tissue disorders and other causes of persistent inflammation (acute phase reactants will cause an increase in the globulin gap).
– Causes of monoclonal gammopathy include MGUS, multiple myeloma, Waldenstrom’s macroglobulinemia, amyloidosis and lymphoma.
– An SPEP (shown below), immunofixation and free light chain assay should be ordered to help determine the etiology of the protein gap. Remember that SPEP is the initial screening test and the sensitivities of serum immunofixation and free light chain assay are higher for detecting the presence of paraproteins. An abnormal free light chain ratio indicates overproduction of either kappa or lambda light chain.
Today in Goldstein Morning Report we presented a case of a 45 year old M with no PMH who was brought in for acute encephalopathy and witnessed seizures. On exam the patient was found to have multiple cranial neuropathies and labs were significant for a positive RPR (1:32). The patient had a lumbar puncture performed which showed 4 WBCs (lymphocytes), glucose 67 and protein 54 and CSF VDRL was found to be reactive.
– Clinical signs of neurosyphilis include meningitis, stroke, acute/chronic encephalopathy, loss of vibration sense, cranial nerve dysfunction and auditory/ophthalmic abnormalities.
– The diagnosis of neurosyphilis is based on clinical suspicion, serologic tests and CSF analysis.
– Remember that CSF abnormalities can occur in early syphilis, and may not be clinically significant in the absence of neurologic signs/symptoms.
– In early neurosyphilis, serum nontreponemal (VDRL, RPR) and treponemal tests (FTA-ABS) are generally reactive, however in late neurosyphilis VDRL and RPR may be nonreactive and FTA-ABS should always be performed.
– CSF-VDRL is highly specific and a reactive test is diagnostic for neurosyphilis, however the sensitivity is much lower.
Diagnosis of neurosyphilis in an HIV- patient
– In patients with a nonreactive CSF-VDRL, treatment depends on further CSF findings.
—> If the CSF WBC>5, treat for neurosyphilis.
—> If the CSF WBC<5 but the CSF protein >45, treat for neurosyphilis.
Diagnosis of neurosyphilis in an HIV+ patient
– Similarly to HIV- patients, further CSF studies must be used to diagnosed neurosyphilis when the CSF-VDRL is negative. However HIV can cause a mild CSF pleocytosis and protein level (especially in those with CD4>200, detectable HIV RNA and not on ART).
–> If the CSF WBC >20, treat for neurosyphilis.
–> If the CSF WBC is 6-20, treat for neurosyphilis if the CD4<200, HIV RNA<50 and on ART
–> If the CSF WBC is ≤5, do not treat.