Dale A. Ellison

Diagnosing cervical biopsies in adolescents: the use of p16 immunohistochemistry to improve reliability and reproducibility.

Objective. To increase the specificity in diagnosing cervical biopsies in adolescents, we evaluated the use of p16 immunohistochemistry (IHC) as an adjuvant test in addition to hematoxylin and eosin (H&E). Materials and Methods. One hundred cervical histological tissues from adolescents were stained with routine H&E and monoclonal p16 (clone E6H4; dilution, 1:25; Dako). One gynecologic pathologist and 3 pediatric pathologists independently reviewed the cases, rendered diagnoses first by using H&E alone, and then added p16 IHC as an adjuvant marker. The interobserver agreement between the gynecologic pathologist and the pediatric pathologists was calculated using &kgr; statistics. Results. The agreement rates between the gynecologic pathologist and all 3 pediatric pathologists were fair (&kgr; = 0.39, 0.36, and 0.37) when only H&E sections were used, and were improved to moderate (&kgr; = 0.53, 0.44, and 0.50) after using p16 IHC in addition to H&E. Conclusions. The evaluation of cervical intraepithelial neoplasia based solely on H&E-stained biopsies may lack interobserver reproducibility. The p16 IHC reduces the number of discrepancies and improves the rate of agreement among pathologists in diagnosing adolescents cervical lesions. The improvement in the diagnosis of cervical biopsies has important implications in the treatment and follow-up of adolescent girls with abnormal cervical cytological diagnoses.

Clonal Telomeric Fusions and Chromosome Instability in a Subcutaneous Sacrococcygeal Myxopapillary Ependymoma

Subcutaneous sacrococcygeal myxopapillary ependymoma (SSME) is a very rare neurologic tumor with no demonstrable connection to the spinal column. Little is known of its etiology, clinical characteristics, or cytogenetics. Giemsa-band analysis revealed a stemline karyotype showing 62 chromosomes. Sidelines within the tumor showed clonal telomeric fusions resulting in dicentric chromosomes involving the fusion of numerous chromosomes. Recurrent telomeric fusions resulted in the progressive deletion of chromosome bands 11q25 and 11q23 and subsequently the entire long arm. This is the first case of a SSME to show clonal cytogenetic aberrations. However, of greater interest is the demonstration of the clonal progression of telomeric fusions resulting in dicentric chromosomes and the subsequent loss of chromosome arms. The observation of clonal telomeric breakage/fusion cycles as progenitor lesions to subsequent deletions provides evidence for telomeric association as an intermediate step in the progression of chromosomal instability.

Malignant Triton Tumor Presenting as a Rectal Mass in an 11-Month-Old

We report the case of an 11-month-old white male who had a family history of neurofibromatosis, had multiple café-au-lait spots on the trunk and extremities, and was diagnosed with a malignant triton tumor of the rectum. To our knowledge, this is the first report of a malignant triton tumor of the rectum and one of the youngest patients reported with the tumor.

Fatal Non-Transplant-Related Epstein-Barr Virus–Associated Atypical Lymphoid Proliferations in Infants and Children: A Clinicopathologic Study

Most Epstein-Barr virus (EBV)–related infections in infants and children are asymptomatic or self-limited mild viral illnesses, but rare cases of a rapidly fatal disorder have been described. Failure of the cellular response to control EBV-related lymphoid proliferation leads to severe disease with multiple complications, including a fatal outcome or development of an EBV-driven, clonal lymphoid neoplasm. In this report we characterize 3 cases of fatal, nontransplant, or immunodeficiency-related EBV infection in very young children with immunophenotypic and molecular evidence of B/natural killer (NK)-T cell clonal expansion. An immunohistochemical staining panel included testing for B-cell antigen (CD20), and T/NK cell antigens including CD2, CD3, CD4, CD8, CD56, CD57, and TIA-1. T-cell and B-cell PCR clonality testing was performed on paraffin tissue specimens to identify clonal populations. The ages of these 3 patients ranged from 22 months to 4 years. Initial clinical presentations included pneumonia, abnormal liver function tests and fever, and lymphadenopathy. The 3 patients died within 17 to 72 days of presentation, and autopsy was performed on 1 patient. All cases demonstrated prominent atypical lymphoid or lymphohistiocytic infiltrates, and necrosis was present in 2 of the 3 cases. The atypical lymphocytes were positive for CD3 (cytoplasmic), CD2, CD8, TIA-1, and CD57 and negative for CD4. We molecularly identified B-cell clones in the 2 tested patients, who also showed evidence of hemophagocytosis. Fatal EBV infection is characterized by a morphologic spectrum with atypical lymphoid infiltrates and variable necrosis. Our molecular studies of these patients suggest a clonally-derived expansive process, most likely driven by EBV infection. Our results also suggest that development of clonality is associated with an aggressive clinical course and may be useful in predicting greater risk for fatal outcome. A high index of suspicion, coupled with appropriate serologic and molecular testing, aids in early recognition and diagnosis of these lymphoproliferative processes.

Soft-Tissue Aneurysmal Bone Cyst: Report of a Case with t(5;17)(q33;p13)

We describe a primary aneurysmal bone cyst (ABC) of the soft tissue of the distal thigh in a 10-year-old girl. Radiographs showed an oblong density in the soft tissue that was consistent with hemorrhage or calcification; the underlying bone was unremarkable. Pathologic findings were consistent with myositis ossificans on gross examination, but numerous hemorrhagic cysts were present in the lesion. Histopathologic findings showed features of an ABC. Cytogenetic analysis of the tumor revealed 46,XX,t(5;17)(q33;p13); 17p13 breakpoints have been reported in intraosseous ABC. Thirteen months after diagnosis, the patient had excellent function and no radiologic evidence of recurrent disease. Soft-tissue ABC is a rare, benign lesion that can have a similar radiologic appearance to myositis ossificans but has a histologic appearance identical to that of its intraosseus counterpart.

Melanotic Neuroectodermal Tumor of Infancy: Report of a Case with Myogenic Differentiation

An 8-month-old boy presented with a 6-week history of a skull mass of the anterior fontanelle. The mass was excised, and the histopathologic features were diagnostic for melanotic neuroectodermal tumor of infancy. The tumor showed focal myogenin positivity, which has not been previously reported in this tumor. The patient has no evidence of recurrent tumor 10 months after the excision. No adjuvant therapy was given. In addition, we stained a case of melanotic neuroectodermal tumor of infancy obtained from Columbus Childrens Hospital; focal myogenin positivity was present.

Hajdu-Cheney Syndrome: Report of a Case

Hajdu-Cheney syndrome is a rare disorder characterized by short stature, joint hypermobility, distinctive craniofacial and skull abnormalities, dental anomalies, and acroosteolysis of the distal phalanges. Cystic kidneys have been associated with some cases. We report a case of a 12-year-old girl with renal failure who underwent bilateral nephrectomies. Histopathological examination revealed polycystic kidneys with numerous nodules located throughout the kidney composed of basaloid epithelial cells.

Tumors of the Autonomic Nervous System

Tumors of the adrenal medulla, extra-adrenal paraganglia of the sympathetic neuroendocrine system, and paraganglia of the head and neck are derivedfrom neural crest cells. These tumors manifest as growing masses and can cause endocrine dysfunction due to unregulated secretion of hormones. Tumors arising in the adrenal medulla (pheochromocytomas) and extraadrenal paraganglia (paragangliomas) usually present in adulthood. Their diagnosis is based on histologic features, immunohistochemical stains, and electron microscopy. These features are reviewed, as are familial syndromes and their associated gene mutations.

Cytogenetic Findings in Pediatric T-Lymphoblastic Lymphomas: One Institution’s Experience and a Review of the Literature

Cytogenetic analyses of lymphomas commonly reveal nonrandom chromosomal abnormalities, but there are relatively few reports in childhood lymphoblastic lymphoma (LL). We retrospectively reviewed G-banded karyotypic analyses performed at Arkansas Children’s Hospital between 1990 and 2004. Six children (2 to 20 years old) had LL that presented as mediastinal or cervical masses and had a T-cell immunophenotype and clonal abnormalities. The cytogenetic findings in these 6 patients were as follows: 46,XX,−7,inv(9)(p11q12),der (12)t(7;12)(q11.2;p13),t(16;18)(p13.1;q21),+22 in patient 1; 47,XX,+9,del(9)(q11q22)x2 in patient 2; 72−119, XY,+X,+1,+1, inv(2) (p11q13),−3,+5,+6,+7,+10,−12,−16, −21,−21,−22,+mar in patient 3; 48,XY,+5,+20,t(7;9) (q32;q34) in patient 4; 47∼48,XX,der(10)t(10;14)(q23; q11.2),+12, del(12)(p12)x2, −14,del(16)(q22q22),+?add (19)(p13.3) in patient 5; and 48∼49,XY,+7,+8,t(11;19) (q23;p?13.3),+der(19)t(11;19)[cp20] in patient 6. Eleven chromosome breakpoints in 6 of our patients (7q11, 12p13, 16p13, 18q21, 9q11, 2p11, 2q13, 7q32, and 7q23) have been reported in other patients with acute lymphoblastic leukemia or LL and involved regions containing TEL, ABL, E2A, MLL, and T-cell receptor-α genes. A review of the cytogenetic findings of these and other cases of LL reveals that clonal aberrations are common and most frequently involve T-cell receptor gene regions. The aberrations show some features similar to those of acute lymphoblastic leukemia and are not unique to LL, thus furnishing additional evidence of the equivalence of these two diseases. The cytogenetic features of LL may be helpful in the diagnosis of pediatric lymphomas and undifferentiated neoplasms.