In 06/01, a white male in his fourth decade presented to the emergency department of a metropolitan county hospital with a 3-month history of an enlarging right inguinal mass. He noted accompanying scrotal swelling, night sweats, and groin pain, rated as 4/10 in severity, intermittent in nature with radiation to the surrounding inguinal area and right testicle.
This patient had been admitted to the same institution one month earlier with the same complaints. At that time, a fine needle biopsy of the right inguinal node was done and the patient was discharged with instructions for medical follow-up. Pain medications were prescribed for symptom control. Before the date of the follow-up visit, the patient returned to the emergency department with the same complaints. The needle biopsy result was subsequently reported as "negative for malignant cells."
Past medical history was significant for infection with Human Immunodeficiency Virus (HIV) and four episodes of pneumocystis carinii pneumonia (most recent in 2000), consistent with a diagnosis of Autoimmune Deficiency Syndrome (AIDS); (a subsequent CD4 count completed in July 2001 was 108/microliter). This patient also reported bilateral hip pain, neuropathic foot pain bilaterally and gastroesophageal reflux disease. Past surgical history revealed repair of a right inguinal hernia as a child, right inguinal fine needle biopsy 5/01, and repair of a left undescended testis as a child. Medications at the time of admission included: efavirenz 600 milligrams (mg) once daily, stavudine 40 mg twice daily, lamivudine 150 mg twice daily, sulfamethoxazole/trimethoprim (800 mg/160 mg) once daily, lansoprazole 15 mg daily, nortryptyline 75 mg daily.
A review of systems was significant for a weight loss of five pounds over the past month and the chronic hip pain reportedly previously diagnosed as osteoarthritis.
At presentation, the oral temperature was 99.1 degrees Fahrenheit and a heart rate of 108; vital signs were otherwise unremarkable. The patient was noted to be conscious, alert and oriented but somewhat agitated; beads of sweat were noted on his forehead. Physical examination was significant for mild pallor, left axillary lymphadenopathy, diffuse abdominal tenderness, mild hepatosplenomegaly and 2+ pitting edema involving the proximal right lower extremity. This edema involved the right inguinal region and extended inferiorly to the upper thigh; right thigh diameter was noticeably larger than the left (objective measurement not recorded). Genital examination revealed a circumcised, thickened, doughy penis and an enlarged right non-erythematous testicle with mild tenderness to palpation/manipulation. The right inguinal area was swollen, firm and tender with massive adenopathy measuring 12 centimeters (cm) by 8 cm; no discharge or warmth to touch was noted. The left groin area revealed a well-healed inguinal scar consistent with prior surgery and non-tender adenopathy recorded as 4 cm by 2 cm without erythema, warmth, or discharge.
Initial laboratory testing included a complete blood count with differential, chemistry panel, coagulation panel, urinalysis, and computerized tomography (CT) scans of the abdomen and pelvis. Blood tests were unremarkable except for mild anemia with hemoglobin of 10.2 grams/deciliter (g/dl). The CT scan revealed extensive retroperitoneal, pelvic, and bilateral inguinal adenopathy [figure ].
Pre-treatment and post-treatment CT Scans showing diffusely enlarged retroperitoneal adenopathy (see arrows) and subsequent disappearance following chemotherapy.
Following an initial assessment in the emergency department, this patient was admitted for further work-up and pain control. Differential diagnoses were focused on infectious and malignant etiologies [table ].
Initial and expanded differential diagnoses for male HIV(+) patient who presented with painful right inguinal adenopathy
Upon admission, additional laboratory studies were ordered including repeat complete blood count with differential, liver profile, Erythrocyte Sedimentation Rate (ESR), protein electrophoresis, and serum immunoelectrophoresis to rule out multiple myeloma, given the chronic hip pain.
CT scan of the chest showed an enlarged right paratracheal lymph node. Radiographs of right hip revealed mixed sclerotic and lytic lesions of the acetabulum and femur. Bone scan showed increased uptake in right femoral head, trochanter and proximal shaft of femur. The differential diagnosis at this point included lymphoma, multiple myeloma, and HIV adenopathy. Surgical and infectious disease consultations were requested.
The infectious disease service noted this patient's immunocompromised status and the possibility of an ineffective febrile response. Accordingly, the possibility of an infectious etiology was expanded to include infectious adenitis, disseminated mycobacterium avium intercellulare (MAC) infection, disseminated tuberculosis, cryptococcosis, histoplasmosis and rhodococcus equi (Nocardia restricta). Histoplasmosis was unlikely as there was no reported travel to histoplasmosis endemic regions. Additional studies were performed: hepatitis profile to rule out hepatitis infection and a viral panel (Human Herpes Virus [HHV]-8, Human T-cell Lymphotrophic Virus [HTLV]-1 & HTLV-11, and Epstein Barr Virus [HBV]), since viral infections have been associated with certain malignancies in HIV-positive patients.
Open biopsy and fine needle re-biopsy of the right inguinal lymph nodes were completed by the surgical service. The specimens from these biopsies were sent to pathology for histologic review, bacterial culture, fungal culture, viral culture, and acid-fast bacilli staining. Flow cytometry and repeat CD4 count and HIV RNA load was performed to assess current immune status and to rule out lymphoma.
The repeat complete blood count revealed normal lymphocyte (3,100 /mm3) and absolute neutrophil counts (9,600/mm3) and stable mild anemia (hemoglobin 10.8 g/dl). ESR was 125 mm/hour. Negative Rapid Plasmin Reagin (RPR) testing served to rule out syphilis. Two sets of blood cultures were negative for bacterial growth. The viral, fungal and bacterial studies, as well as acid-fast testing on the biopsied lymph node material were all negative. Flow cytometry was negative. Protein electrophoresis showed high alpha 2 levels, a faint Immunoglobulin G kappa band, and low albumin, essentially ruling out multiple myeloma. The hepatitis panel was negative. A liver function panel revealed an alanine aminotransaminase level of 194 units/liter, alkaline phosphatase of 253 units/liter and lactase dehydrogenase of 726 IU/liter, essentially unchanged from values noted at time of admission.
An ultrasensitive HIV RNA assay was undetectable and the CD4 count, which was initially 27/microliter, became undetectable during the hospital course. The patient's low CD4 was determined to be secondary to abnormal lymphocyte processing and cell turnover resulting from his current disease process, rather than failure of the highly active anti-retroviral therapy (HAART) and patient was continued on HAART by the infectious disease consultant.
Histologic evaluation revealed atrophic lymphoid follicles with small germinal centers and cellular reticular stroma with increased populations of plasma cells (see Figure and Figure ). A review of these specimens by pathology staff at a nearby comprehensive cancer center noted "florid HIV-associated plasma cell hyperplasia" and suggested the possibility of Castleman's Disease since this disorder is a plasma cell variant associated with interleukin 6 (IL-6) syndrome. Immunohistochemical stains demonstrated both kappa and lambda positive cells, which are non-specific pathologic findings in Castleman's disease as well as other malignant conditions.
Plasma cell infiltrate in inguinal lymph node biopsy. Atrophic follicles (magnification 40×). Bottom.
Plasma cells are identified by their eccentric, clock-face nucleus and pale perinuclear cytoplasmic crescent. Staining by hematoxylin-eosin stain (magnification 400×).
The patient's clinical presentation of non-infectious lymphadenopathy (all cultures negative), in combination with the absence of typical pathognomic features supporting a diagnosis of Castleman's Disease, necessitated a comprehensive review of published literature by the in-patient medical team. Following completion of this review, along with input from the infectious disease consultant, it was determined that this patient's diagnosis was a multicentric type of Castleman's Disease.
Accordingly the patient was started on a chemotherapy regimen of doxorubicin, vincristine, cyclophosphamide and prednisone by the hematology/oncology service. The patient appeared to tolerate this well, achieving some resolution of edema as well as adequate pain control.
This patient was discharged to home on day 3 following the first course of chemotherapy, with instructions for further out-patient follow-up with the oncologist. This patient received a total of six courses of chemotherapy and has remained in remission approximately 18 months following diagnosis (see figure for post-treatment CT scans), although he continues to complain of hip pain.