EURAMOS-1, an international randomised study for osteosarcoma: results from pre-randomisation treatment.

BACKGROUND: Four international study groups undertook a large study in resectable osteosarcoma, which included two randomised controlled trials, to determine the effect on survival of changing post-operative chemotherapy based on histological response. PATIENTS AND METHODS: Patients with resectable osteosarcoma aged ≤40 years were treated with the MAP regimen, comprising pre-operatively of two 5-week cycles of cisplatin 120 mg/m(2), doxorubicin 75 mg/m(2), methotrexate 12 g/m(2) × 2 (MAP) and post-operatively two further cycles of MAP and two cycles of just MA. Patients were randomised after surgery. Those with ≥10% viable tumour in the resected specimen received MAP or MAP with ifosfamide and etoposide. Those with <10% viable tumour were allocated to MAP or MAP followed by pegylated interferon. Longitudinal evaluation of quality of life was undertaken. RESULTS: Recruitment was completed to the largest osteosarcoma study to date in 75 months. Commencing March 2005, 2260 patients were registered from 326 centres across 17 countries. About 1334 of 2260 registered patients (59%) were randomised. Pre-operative chemotherapy was completed according to protocol in 94%. Grade 3-4 neutropenia affected 83% of cycles and 59% were complicated by infection. There were three (0.13%) deaths related to pre-operative chemotherapy. At definitive surgery, 50% of patients had at least 90% necrosis in the resected specimen. CONCLUSIONS: New models of collaboration are required to successfully conduct trials to improve outcomes of patients with rare cancers; EURAMOS-1 demonstrates achievability. Considerable regulatory, financial and operational challenges must be overcome to develop similar studies in the future. The trial is registered as NCT00134030 and ISRCTN 67613327.

Which patients with microscopic disease and rhabdomyosarcoma experience relapse after therapy? A report from the soft tissue sarcoma committee of the children's oncology group.

PURPOSE: To identify which patients with rhabdomyosarcoma and microscopic residual disease (group II) are likely to not respond to therapy. PATIENTS AND METHODS: Six hundred ninety-five patients with group II tumors received chemotherapy and 90% received radiation therapy on Intergroup Rhabdomyosarcoma Study (IRS)-I to IRS-IV (1972 to 1997). Tumors were subgrouped depending on the presence of microscopic residual disease only (subgroup IIa), resected positive regional lymph nodes, (subgroup IIb), or microscopic residual disease and resected positive regional lymph nodes (subgroup IIc). RESULTS: Overall, the 5-year failure-free survival rate (FFSR) was 73%, and patients with embryonal rhabdomyosarcoma treated on IRS-IV fared especially well (5-year FFSR, 93%; n = 90). Five-year FFSRs differed significantly by subgroup (IIa, 75% and n = 506; IIb, 74% and n = 101; IIc, 58% and n = 88; P = .0037) and treatment (IRS-I, 68%; IRS-II, 67%; IRS-III, 75%; IRS-IV, 87%; P < .001). Multivariate analysis revealed positive associations between primary site (favorable), histology (embryonal), subgroup IIa or IIb, treatment (IRS-III/IV), and better FFSRs. Patterns of treatment failure revealed local failure to be 8%, regional failure, 4%, and distant failure, 14%. The relapse pattern noted over the course of IRS-I to IRS-IV shows a decrease in the systemic relapse rates, particularly for patients with embryonal histology, suggesting that improvement in FFSRs is primarily a result of improved chemotherapy. CONCLUSION: Group II rhabdomyosarcoma has an excellent prognosis with contemporary therapy as used in IRS-III/IV, and those less likely to respond can be identified using prognostic factors: histology, subgroup, and primary site. Patients with embryonal rhabdomyosarcoma are generally cured, although patients with alveolar rhabdomyosarcoma or undifferentiated sarcoma, particularly subgroup IIc at unfavorable sites, continue to need better therapy.

Routine brain imaging is unwarranted in asymptomatic patients with rhabdomyosarcoma arising outside of the head and neck region that is metastatic at diagnosis: a report from the Intergroup Rhabdomyosarcoma Study Group.

BACKGROUND: To the authors' knowledge, the incidence of brain metastases at the time of diagnosis in children with metastatic rhabdomyosarcoma (RMS) arising outside the head and neck region is unknown, and routine imaging to identify metastatic brain involvement is costly. METHODS: The authors retrospectively reviewed the results of computed tomography (CT) or magnetic resonance imaging (MRI) scans of the head, which was mandated by protocol, in patients with metastatic RMS arising outside the head and neck region who were enrolled on the fourth Intergroup Rhabdomyosarcoma Study (IRS-IV; 1991--1997). RESULTS: Of 100 eligible patients with metastatic RMS arising outside the head and neck region, 56 (56%) underwent head CT (n = 51) and/or MRI (n = 11) scans. Seven of these 56 patients (12.5%) had abnormal scans. Three patients with physical findings suggesting head or neck pathology underwent imaging that confirmed the presence of metastases in bone (one patient), orbit (one patient), or lymph nodes (one patient). One patient who presented with seizures had imaging findings consistent with cerebral embolic infarctions. Of three asymptomatic patients, one had bone metastases that also were identified on skeletal survey and one had bone metastases in the base of the skull that were not identified on bone scan. The remaining asymptomatic patient had a retroperitoneal paraspinal tumor with spinal canal extension and subsequently developed leptomeningeal disease dissemination. CONCLUSIONS: Brain metastases are uncommon at the time of initial diagnosis of metastatic RMS arising outside the head and neck region, and the majority of abnormalities detected on head CT or MRI scans are evident clinically or on other imaging studies. Patients with clinical findings suggesting intracranial pathology and those with paraspinal tumors may benefit from brain imaging, but cost savings may be realized by foregoing imaging in patients without these features.

Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group.

PURPOSE: This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs (vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients with metastatic rhabdomyosarcoma. PATIENTS AND METHODS: One hundred twenty-eight patients were randomly assigned to phase II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC), chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. RESULTS: Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated with either regimen (VM, 74%; IE, 79%; P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS: 55% vs. 27%; P = 0.012). CONCLUSIONS: Although the VM-containing regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered, and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.

Cytokine and matrix metalloproteinase expression in pigmented villonodular synovitis may mediate bone and cartilage destruction.

BACKGROUND: Pigmented villonodular synovitis (PVNS) is characterized by hypervascular proliferative synovium containing multinucleated giant cells, macrophages, and hemosiderin. The destruction of articular cartilage and erosion of periarticular bone is thought to be mediated by matrix metalloproteinases (MMPs). Expression of MMPs in some tumors appears to be stimulated through local production of cytokines, and several specific cytokines (TNF alpha, IL-1, and IL-6) play an important role in the stimulation of osteoclastic bone resorption. The role of cytokine secretion and regulation of MMP production in PVNS has not been investigated. DESIGN: In the present study, ten specimens from eight patients (ages 19 to 80) were evaluated histologically according to a modified Mirra classification and immunohistochemically (IHC) for the expression of MMP-9 (92 kDa gelatinase B), tumor necrosis factor alpha (TNF alpha), interleukin 1-beta (IL-1 beta), and interleukin 6 (IL-6). Localization of IL-6 and TNF alpha production was confirmed by in situ hybridization (ISH) for mRNA. RESULTS: All specimens, regardless of location (six knees, one ankle, one subtalar joint), showed diffuse and intense immunoreactivity for cytokines in the giant cells and synovial cells, and less intense and diffuse staining in the activated macrophages. Staining in the fibroblastic elements was minimal. In situ hybridization for TNF alpha and IL-6 mRNA mirrored the immunohistochemistry results, although the IL-6 staining was weaker than that for TNF alpha. Immunoreactivity for MMP-9 was diffuse and strong in giant cells, diffuse and moderate in synovial cells, and focal and moderate to strong in macrophages. In contrast, normal synovium demonstrated focal, moderate immunoreactivity for IL-1 beta, IL-6, TNF alpha and MMP-9 localized in the synovial lining cells. CONCLUSION: These findings suggest that periarticular bone resorption and cartilage destruction which characterize PVNS may be related to the expression of inflammatory cytokines, which in turn stimulate MMP production.

Histopathologic practices for esophageal biopsy specimens: survey results and implications for surveillance in patients with Barrett's esophagus.

A clinically valuable interpretation of esophageal biopsy specimens begins with well-prepared histologic sections. This may be especially true for reflux esophagitis and Barrett's glandular dysplasia. To determine exactly which histologic procedures are used by experts in gastrointestinal pathology, a checklist survey was mailed to 50 members of the Gastrointestinal Pathology Society. Responses were received from 42 (84%). Formalin, used 80% of the time, is overwhelmingly the most popular fixative. Orientation of biopsy material before further processing is performed in 36% of the institutions, most often (53%) by an endoscopy technician. The most frequently used (60%) substrate for orientation is filter material. The most common (83%) routine procedure uses only H&E staining. Others routinely add a mucin reaction to the H&E. Eleven different practices for sectioning are used; the most common (43%) is serial step sectioning at 3 levels. One third of the responders had a formal surveillance program for patients with Barrett's esophagus. For esophageal biopsy specimens, a broad spectrum of histologic practices exists. Trends for the more complex histotechnologic procedures to be used by those involved in screening for dysplastic Barrett's epithelium are evident.

P-glycoprotein expression in cartilaginous tumors.

BACKGROUND AND OBJECTIVES: Malignant cartilage tumors demonstrate chemotherapeutic resistance through undetermined mechanisms. P-glycoprotein is the protein product of the multiple drug resistance gene 1 (MDR-1) and confers multidrug chemotherapeutic resistance in a variety of malignancies. METHODS: MDR-1 expression was examined in 55 benign and malignant cartilage tumor specimens by immunohistochemistry using C219, C494, and JSB-1 antibodies, and by in situ hybridization with an MDR-1 specific oligonucleotide cDNA probe. RESULTS: Constitutive expression of P-glycoprotein was observed in all benign and malignant cartilage tumor specimens with a similar pattern of immunohistochemical staining present with all three antibodies. In benign tumors and low grade chondrosarcomas, the staining pattern was weak to intermediate and localized to clusters of cells. However, higher grade-tumors (Grade II and III) expressed P-glycoprotein in a higher percentage of cells and with more intense staining. P-glycoprotein expression was absent in normal human articular cartilage, but was focally present in costal and growth plate cartilage. The immunohistochemistry results were confirmed by in situ hybridization in 10 cases. CONCLUSIONS: P-glycoprotein is expressed constitutively in cartilaginous tumors, with greatest expression in high grade malignancies. The findings may account for the resistance of cartilage tumors to chemotherapeutic agents.

Osteoclasts constitutively express regulators of bone resorption: an immunohistochemical and in situ hybridization study.

Bone resorption is controlled by the local production of soluble regulatory molecules within the marrow microenvironment that mediate osteoclast recruitment, differentiation, and activation. Under normal conditions osteoclasts are rarely seen; in many pathologic states, however, the number of osteoclasts is dramatically increased, resulting in a net-loss of bone mass. The role of the osteoclasts as autocrine regulators of bone resorption in either normal or pathologic conditions has not been extensively investigated. The expression of IL-1 beta, IL-6, and TNF-alpha was examined in osteoclasts by immunohistochemistry under conditions of normal, reactive, and pathologic bone resorption, including growth plate (3 cases), fracture callus (5 cases), osteomyelitis (3 cases), Paget's disease (6 cases), giant-cell tumor of bone (14 cases), and brown tumor of hyperparathyroidism (2 cases). In each case, osteoclasts demonstrated immunoreactivity for IL-1 beta, IL-6, and TNF-alpha. In areas of active bone resorption, the intensity and uniformity of staining among the various conditions were similar, suggesting constitutive expression of these cytokines by activated osteoclasts. Giant-cell tumors of bone showed cytokine reactivity in over half of the giant cells, whereas stromal cells showed scattered staining. In acute osteomyelitis, inflammatory cells (mainly macrophages) and osteoclasts were intensely positive for all three cytokines. The immunohistochemical findings were confirmed by in situ hybridization using probes specific for IL-6 and TNF-alpha, the pattern of mRNA expression paralleled that of immunoreactivity for these cytokines. These findings support the notion of autocrine/paracrine regulation of bone remodeling by osteoclasts. Because overproduction of these cytokines may enhance bone resorption through the stimulation of osteoclast progenitor cells as well as mature osteoclasts, pathologic bone lesions with a large increase in the number of osteoclasts may be self-perpetuating. Alteration in the synthesis, secretion, or activity of these important regulatory molecules may in turn alter bone remodeling and loss.

Fine-needle aspiration biopsy of synovial sarcoma. A cytomorphologic analysis of primary, recurrent, and metastatic tumors.

Thirteen fine-needle aspiration specimens from 10 patients with histologically proven synovial sarcoma are described. The aspiration biopsy specimens were obtained from the primary tumor in five cases, locally recurrent tumors in four cases, pulmonary metastases in three cases, and mediastinal metastasis in one case. Patient's ages ranged from 22 years to 65 years; there were four women and six men. All cases had a confirmation biopsy and/or resection specimen that were reviewed. Histologic subtypes included monophasic fibrous (5 cases), monophasic epithelial (1 case), biphasic (3 cases), and poorly differentiated (1 case). The majority of the aspiration biopsy specimens were similar with moderate to marked smear cellularity dominated by cohesive clusters of spindle-shaped cells with ovoid, hyperchromatic nuclei and scanty tapering cytoplasm. Nucleoli were not prominent. Epithelial tumor cells with ovoid to round, mostly regular, centrally to eccentrically located nuclei, surrounded by scant to abundant cytoplasm predominated in one case (monophasic epithelial) and were admixed with spindle cells in a second (classical biphasic). Multi-nucleated tumor giant cells were not observed in any of the tumors. In biphasic synovial sarcoma, the neoplastic spindle cells are generally more numerous and frequent than the epithelial cells, making distinction from monophasic synovial sarcoma or other spindle cell soft tissue tumors difficult. Although synovial sarcoma may be diagnosed by fine-needle aspiration cytology, clinical correlation, especially in monophasic types, is necessary to minimize errors in sarcoma classification.

Mollaret's meningitis: case report with immunocytochemical and polymerase chain reaction amplification studies.

Mollaret's meningitis is a rare disease with a characteristic clinical course and distinctive cerebrospinal fluid (CSF) cytology. Although Mollaret originally described the large mononuclear cells seen in the CSF as endothelial, subsequent ultrastructural and immunocytochemical studies support a monocyte/macrophage lineage for these cells. To data, the pathogenesis of this entity remains uncertain, although an association with herpes simplex virus (HSV) has been reported in rare cases. In the current case study, immunocytochemistry for factor VIII-related antigen, leukocyte common antigen, and macrophage-specific antigen were performed and provide additional evidence of a monocyte/macrophage lineage for Mollaret cells. Polymerase chain reaction amplification for HSV DNA was done to further explore one possible etiology for this disease, but was negative.

Fine-needle aspiration cytology of metastatic small cell carcinoma of the colon: a report of three cases.

Small cell carcinoma of the large intestine is a rare, extremely aggressive malignancy often associated with an overlying adenoma. We report three cases of metastatic small cell carcinoma of the colon diagnosed by fine-needle aspiration (FNA) biopsy. Two of the patients were women (ages 33 and 46 yr old) and one was a man (69 yr old). FNA biopsy established the diagnosis of metastatic small cell carcinoma involving the liver (2 cases) and soft tissue of the scapular region (1 case). In one patient, the FNA diagnosis of hepatic metastases preceded identification of the primary site. Subsequently, the patient was found to have a small cell carcinoma subadjacent to a colonic villous adenoma, illustrating the importance of investigating villous lesions of the colon in patients with metastatic small cell carcinoma of unknown primary origin (especially in non-smokers). All three cases showed the characteristic cytologic features of small cell carcinoma. Ancillary studies performed on aspirated material confirmed the diagnosis of small cell carcinoma in one case. Immunocytochemical studies revealed punctate cytokeratin and diffuse neuron-specific enolase (NSE) positivity of the malignant cells. Ultrastructurally neurosecretory granules were evident. To the best of our knowledge, this is the first FNA cytologic report of metastatic small cell carcinoma of the large intestine. This FNA report also demonstrates when a small cell carcinoma is detected in a metastatic site in a patient lacking a lung primary, a likely primary site could be adjacent or beneath a polypoid lesion of the colon.

Extraosseous primary and recurrent giant cell tumors: transforming growth factor-beta1 and -beta2 expression may explain metaplastic bone formation.

Giant cell tumor (GCT) of bone is a locally aggressive neoplasm with a high incidence of recurrence, usually at the site of previous osseous involvement. Primary and recurrent intraosseous lesions typically are lytic and do not show evidence of tumor-associated osteogenesis. Rarely, GCT recurs or is primary within soft tissue, and not infrequently, these extraosseous lesions show metaplastic bone formation that is visible radiographically. The authors report two recurrent and one primary case of extraosseous GCT, all of which exhibited significant deposits of metaplastic bone localized to the periphery of the lesions. In situ hybridization showed messenger RNA (mRNA) for transforming growth factor beta1 (TGF-beta1) and transforming growth factor beta2 (TGF-beta2) in neoplastic stromal cells and osteoclast-like giant cells within the recurrent and primary extraosseous tumors as well as in active osteoblasts on the surfaces of recently formed spicules of metaplastic bone. In situ hybridization also revealed mRNA for TGF-beta1 and TGF-beta2 in primary intraosseous tumors from these cases and from four cases in which neither extraosseous recurrence nor osseous metaplasia was identified. In the microenvironment of the extraosseous soft tissue, production of these osteoinductive growth factors by GCT may have a paracrine effect on mesenchymal progenitor cells, thereby stimulating the osteoblastic differentiation and metaplastic bone formation associated with these lesions.

Amniotic fluid interleukin-10 concentrations increase through pregnancy and are elevated in patients with preterm labor associated with intrauterine infection.

OBJECTIVE: To better understand the role of the antiinflammatory cytokine interleukin-10 in preterm labor and infection, we evaluated the amniotic fluid interleukin-10 concentrations through pregnancy, in term, and in preterm labor. STUDY DESIGN: Amniotic fluid interleukin-10 levels were measured in 147 women throughout pregnancy including patients in the second trimester, patients at term with and without labor, and in patients in preterm labor with and without an intrauterine infection. We compared the amniotic fluid interleukin-10 concentrations among these five groups using the Mann-Whitney U test. RESULTS: Amniotic fluid interleukin-10 was detected in 70% to 91% of patients in each of the five study groups. Higher concentrations were found at term compared with the second trimester (p < 0.001) and concentrations were significantly greater in patients with preterm labor and intrauterine infection compared with those patients in preterm labor without infection (p < 0.001), patients at term in labor (p < 0.001), or patients at term not in labor (p < 0.001). When the patients in preterm labor with infection were analyzed by gestational age, those patients at < 30 weeks had significantly higher amniotic fluid concentrations of interleukin-10 (p = 0.014). CONCLUSIONS: Interleukin-10 was present in the amniotic fluid of the majority of pregnancies, with higher concentrations found at term compared with the second trimester. Intrauterine infection was associated with significantly increased concentrations, with even higher concentrations found in the very premature pregnancies. Interleukin-10 has a prominent yet undefined role in pregnancy and preterm labor complicated by intrauterine infection.

Extra-adrenal myelolipoma: report of two cases.

Myelolipomas are benign tumors composed of an admixture of mature adipose tissue and normal hematopoietic cells. The vast majority occur within the adrenal glands, but several extra-adrenal myelolipomas (EAMLs) have been reported. The typical EAML is a solitary, well-defined mass within the abdomen, most commonly in the retroperitoneal presacral area. EAMLs may produce symptoms related to their mass effect, but they are occasionally incidental findings. Most commonly, the patient is older than 40 years and has no hematologic abnormalities. It is important to distinguish EAMLs from other soft tissue tumors, in particular liposarcomas, myxoid malignant fibrous histiocytomas, and extramedullary hematopoietic tumors. We discuss two cases of EAML. The first was in the retroperitoneum of a 76-year-old woman. It is the largest EAML ever reported, measuring 26 cm x 15 cm x 11 cm. The second, a presacral mass in a 68-year-old man, was diagnosed preoperatively by percutaneous computed tomography-guided fine needle aspiration biopsy. Preoperative diagnosis facilitated surgical management in this case. We discuss the clinical, radiologic, and pathologic characteristics and the differential diagnosis of this rare entity.

Sudden death in epilepsy due to an isolated subependymal giant cell astrocytoma of the septum pellucidum.

We report a case of sudden unexpected death in an individual with epilepsy. Autopsy revealed a subependymal giant cell astrocytoma of the septum pellucidum, but there were no other lesions of tuberous sclerosis. We discuss sudden death in epilepsy, deaths related to primary brain tumors, the pathology of subependymal giant cell astrocytoma, and whether or not such a tumor can exist outside the setting of tuberous sclerosis. We also discuss the implications such findings may have on surviving family members, as well as the important role of the forensic pathologist in such cases.

Relationship of DNA ploidy to histology and prognosis in rhabdomyosarcoma. Comparison of flow cytometry and image analysis.

BACKGROUND: Although DNA ploidy correlates with prognosis in certain childhood cancers, e.g., neuroblastoma, its significance in rhabdomyosarcoma (RMS) is unclear and controversial. METHODS: Ploidy by flow cytometry (FCM) and image analysis (IA) in 26 of 27 children with RMS (17 embryonal, 3 mixed embryonal/alveolar, 5 alveolar, 1 anaplastic, 1 ectomesenchymoma) and 4 adults with pleomorphic RMS were evaluated. Statistical comparisons were analyzed between DNA content and gender, age, localization, Intergroup Rhabdomyosarcoma Study (IRS) group, and histopathologic subtype. Survival analyses were performed by the Kaplan-Meier test using the approximate chi-square statistic for the log rank test. RESULTS: The concordance rate between FCM and IA was 26 of 30 (87%); FCM was not performed in one tumor. Image analysis was more sensitive than FCM in detecting aneuploidy. Furthermore, DNA content was associated significantly with histologic subtype (P = 0.031); embryonal histology commonly was hyperdiploid (mean, 1.44; median, 1.27), whereas alveolar histology usually was near-tetraploid (mean, 1.83; median, 1.95). All four adult patients with pleomorphic RMS were aneuploid, with one showing multiple DNA peaks. No correlation between DNA content and survival was observed in the children with RMS. However, IRS group (P = 0.011) and patient age (P = 0.036) were independent prognostic indicators significantly related to survival. All adult patients died of their disease. CONCLUSIONS: Although ploidy correlates with histologic subtype, DNA content is not significantly predictive of prognosis in patients with RMS. Age at diagnosis and IRS group are independent predictors of clinical outcome in children with RMS.

Cytologic identification of Toxoplasma gondii from vitreous fluid.

A 75-year-old man presented with a diffuse necrotizing retinitis in his left eye. Although his condition was initially diagnosed as acute retinal necrosis syndrome, the serologic test results were interpreted as indicating recurrent toxoplasmosis retinitis. Cytopathologic examination of the vitreous following pars plana vitrectomy for repair of a retinal detachment revealed Toxoplasma organisms. The observation of Toxoplasma gondii in the vitreous specimen confirmed our clinical diagnosis and helped guide treatment of the patient.

Histiocytoid cardiomyopathy: case report and literature review.

The sudden death of an infant may be due to a variety of causes. In such cases, complete autopsy with radiologic, gross, microscopic, and toxicologic examination is warranted. We present a case of a previously healthy 15-month-old girl with no known disease, who experienced witnessed cardiac arrest, ventricular fibrillation, and death. Complete postmortem examination revealed histiocytoid cardiomyopathy as the cause of death. Histiocytoid cardiomyopathy is a rare infantile cardiac-muscle disorder characterized by the presence of enlarged, polygonal subendocardial myocytes which, by light microscopy, lack normal striations, and instead have granular, faintly eosinophilic cytoplasm. Ultrastructurally, the myocytes contain numerous mitochondria and markedly reduced numbers of myofibrils. Clinically, the disorder is characterized by cardiac arrhythmias and/or sudden death occurring in children under the age of two years. We discuss the differential diagnosis, proposed theories of etiology, and the pathology of this rare entity.