Enlarging Parietal Mass with Lytic Skull Lesion

A 17-year-old female patient with past medical history significant for acute lymphoblastic leukemia diagnosed 20 months before this illness presented with a 1-month history of a progressively enlarging head mass in the right posterior parietal region. The patient denied any pain or redness around the mass. However, 2 weeks before admission, she noted a significantly rapid increase in swelling. She reported some intermittent blurry vision in the last 2 weeks. There was no history of head trauma, sensory or motor symptoms, headaches, dizziness, nausea, vomiting, fever, chills, weight loss or fatigue. The patient had never noticed any other lesions on her head. She was in the maintenance phase of acute lymphoblastic leukemia treatment, consisting of 6-mercaptopurine, vincristine, prednisone, intrathecal methotrexate and trimethoprim-sulfamethoxazole prophylaxis. A radiograph of the calvarium revealed a well-defined right parietal lytic lesion on the day of presentation to our institution. An MRI of the head revealed a right parietal 2 cm rim-enhancing lesion involving the inner and outer tables of the right parietal calvarium. There was a small amount of enhancing tissue extending along the subgaleal surface and the superficial margin of the lesion. The brain was normal, and there were no other calvarial lesions (Figs. 1 and 2).FIGURE 1.: Coronal postcontrast T1 image showing a heterogeneous enhanced mass.FIGURE 2.: Axial T1 post contrast flair image showing thick rimmed lesion with enhancement.The patient lived in Bakersfield, CA and was an active athlete in both swimming and yoga. She denied any interference with physical activity. She also denied substance abuse or sexual activity. There was 1 dog at home and no history of contact with birds. Physical examination revealed a young woman in no apparent distress with normal vital signs and a weight of 53 kg. Examination of her head revealed a soft tender mass, 2 cm in diameter, over the right posterior parietal region. Neurologic examination showed intact cranial nerves, normal sensation, normal motor strength but with decreased deep tendon reflexes on the left lower extremity and normal deep tendon reflexes on the right. There were no signs of meningismus. The remainder of the physical examination was normal. Neurosurgical evaluation was requested for an excisional biopsy. Intraoperatively pus was noted in the capsule of the right posterior parietal skull lesion with erosion through the parietal bone to the dura mater. The patient underwent a craniectomy of ~4–5 cm in diameter and recovered without neurologic sequelae. Broad spectrum antimicrobial therapy consisting of cefotaxime, vancomycin and metronidazole was initiated. Further microbiologic identification revealed the diagnosis and led to further evaluation. Denouement Continued from p. 589 The Gram stain from the right parietal mass revealed moderate numbers of yeast organisms, and the bacterial cultures grew yeast within the first 24 h. The patient was treated with liposomal amphotericin B and 5-fluorocy-tosine for suspected cryptococcal infection. Yeast grew on both bacterial and fungal cultures and was identified as Cryptococcus neoformans. The minimum inhibitory concentrations (MIC) of antifungal agents against this organism included 1 μg/ml for amphotericin B, 2 μg/ml for fluconazole and 0.5 μg/ml for 5-fluorocytosine. Histopathologic examination of the surgical specimen revealed evidence of osteonecrosis and osteomyelitis. Gomorimethenamine-silver, mucicarmine, and periodic acid-Schiff stains confirmed the presence of cryptococcal organisms. The diagnosis of cryptococcal osteomyelitis of the skull led to further evaluations to determine the extent of disease. Serum cryptococcal antigen by enzyme immunoassay (Premier Cryptococcal Antigen EIA; Meridian Bioscience, Inc., Cincinnati, OH) was positive at 1/97 on day 1 of treatment, peaked to 1/107 on day 2 and declined to 1/3 on day 42 and 1/11 on day 84 of treatment. A cerebrospinal fluid (CSF) cryptococcal antigen test was positive with a titer of 1/2. CSF fluid analysis revealed < 1 red blood cell/mm3, < 1 white blood cell/mm3, glucose of 57 mg/dl and protein of 25 mg/dl. Fungal CSF stains revealed rare yeast, and culture grew Cryptococcus. Follow-up fungal stain and culture of CSF on days 9, 42 and 84 were negative. CSF cryptococcal antigen titer decreased to 1/1 by day 84. Erythrocyte sedimentation rates was 46 mm/h (Wintrobe) at baseline and decreased to 18 mm/h (Westergren) on day 84 of illness. C-reactive protein values were normal since the beginning of treatment. Fungal blood and urine cultures were negative for Cryptococcus. During hospitalization, CD4 T cell lymphopenia was noted with an absolute CD4 T cell count of 190/mm3. Other T cell subset values were normal. A human immunodeficiency virus antibody screen was negative. Computed tomography imaging of the chest demonstrated the presence of right anterolateral middle lobe and lateral right lower lobe hyperdense nodules without involvement of the ribs. Computed tomography of the abdomen and pelvis revealed normal liver, spleen and kidneys. A nuclear bone scan was significant for abnormal increased tracer uptake only in the right parietal skull. After completion of liposomal amphotericin B for 3 weeks and 5-fluorocytosine for 2 weeks, the regimen was changed to oral fluconazole 800 mg/day divided twice a day with long term suppressive therapy at a lower dose planned for the duration of chemotherapy and until absolute CD4 T cell counts became normal. Cryptococcosis is caused by an encapsulated yeast-like fungus, C. neoformans. Most clinical disease involves central nervous system, lungs, skin and bones. 1 Immunocompromised patients with AIDS may present with cryptococcal meningitis or pulmonary disease. Pediatric patients with HIV infection may have varied clinical presentations with nonspecific findings including fever, malaise, headache or fulminant presentations with meningitis, cryptococcemia or disseminated disease. 2 Cryptococcal disease has been reported in pediatric patients who are receiving immunosuppressive therapy for leukemia, lymphoma or Hodgkin disease or are the recipients of solid organ or bone marrow transplantation. 3–5 Individuals who are immunocompetent may develop symptoms after exposure to birds and inhalation of the fungus from pigeon feces. After inhalation, hematogenous dissemination can occur with systemic infection occurring mainly in immunocompromised individuals. Central nervous system disease can present with symptoms of headache, fever, nausea, vomiting, or nuchal rigidity. Other neurologic presentations include visual disturbances such as diplopia, photophobia, papilledema, focal neurologic deficits, seizures, altered mental status or cerebellar dysfunction. Cryptococcal osteomyelitis has been reported in 5–10% of patients with disseminated cryptococcosis. 6–10 A review of 39 cases by Behrman et al. 6 included patients age 16 months–80 years with clinical symptoms of soft tissue swelling and/or tenderness after systemic infection. Radiographic evidence usually demonstrates osteolytic lesions with no surrounding sclerotic or periosteal changes. Bone sequestration and a soft mass overlying the affected area have also been described. 6,8,9 Although multiple sites have been identified, most patients present with an isolated bone lesion. Sites that have been reported with osteomyelitis included vertebra, femur, tibia, rib, humerus, clavicle, pelvis and scapula. In one review, a single site was identified in 30 of 40 (75%) patients with 1 bone involved, compared with 10 of 40 (25%) patients with multiple bone sites involved. 7 Involvement of the skull (among other sites) has been reported by Armonda et al. 10 One case included a similar patient with left temporal scalp swelling corresponding to a lytic bone lesion on radiograph. This patient had immunosuppression and unrecognized pulmonary disease with probable hematogenous spread and subsequent osteomyelitis of the skull. The CSF analysis did not show evidence of meningitis, but the antigen test and cultures were positive. The question remains whether the lesion eroded through the dura to involve the CSF or if there was central nervous system extension occurring during excision and debridement. This report serves to stress the importance of close follow-up of children with acute lymphoblastic leukemia who are being treated with less intense immunosuppressive maintenance chemotherapy. These children are at risk for a variety of potentially life-threatening opportunistic infections and require regular clinical evaluations during the maintenance phase of chemotherapy and for the first year after discontinuation of immunosuppressive regimens.