Victor Saldivar

Viral-associated trichodysplasia spinulosa: a case with electron microscopic and molecular detection of the trichodysplasia spinulosa-associated human polyomavirus

Trichodysplasia spinulosa (TS) is a folliculocentric and clinically papular dermatological disorder occurring in the setting of immunosuppression typically in association with solid organ transplantation or hematolymphoid malignancies. We report the occurrence of TS in a 7‐year‐old girl with Down syndrome and pre‐B‐acute lymphoblastic leukemia who was completing chemotherapy at onset. The patients affected follicles were dilated by an expansion of a dystrophic follicular inner root sheath cell population displaying enlarged trichohyaline cytoplasmic granules and progressing centrally to keratotic and parakeratotic debris, and superficially demonstrating some diminutive hair shaft‐like material within the keratotic spicules. Electron microscopic studies of a follicular lesion showed extracellular viral particles suggestive of a polyomavirus within the central follicular keratotic debris. DNA polymerase chain reaction (PCR) and gene sequencing studies, performed on the tissue of the microscopic slide and paraffin block, for the recently identified TS‐associated polyomavirus (TSPyV) resulted as positive for TSPyV. PCR for the Merkel cell polyomavirus was negative. To date, this case is unique in representing the first case of TS confirmed by electron microscopy in which a related viral pathogen has been molecularly identified. An additional 19 reported cases classifiable as TS are tabulated and reviewed.

Glioblastoma multiforme masquerading as a pleomorphic xanthoastrocytoma

Since its first description by Kepes in 1979, pleomorphic xanthoastrocytoma (PXA) has been considered a tumor with a benign course. Two cases are presented here that support the concept that PXA may be more accurately considered part of a spectrum of astrocytomas that occasionally may act aggressively. These cases represent astrocytomas with PXA components and are characterized by meningeal proximity, a high number of mitoses, and subsequently aggressive clinical behavior. The importance of recognizing the potential of a “benign” PXA to transform into a malignant entity has obvious implications for the therapeutic management of these tumors.

Cytogenetic and molecular evaluation of clinically aggressive esthesioneuroblastoma.

We report a 16-year-old boy with esthesioneuroblastoma that presented with a unilateral tumor extending to the maxillary sinus and periorbital region. Despite initial therapy with gross resection, 5,682 cGy to the tumor bed and chemotherapy, the patient subsequently had a rapid local recurrence with distant metastases. Immunocytochemical, ultrastructural, cytogenetic, and molecular techniques were performed to determine if this tumor was biologically similar to childhood neuroblastoma. Urinary excretion of vanillylmandelic acid (VMA) and homovanillic acid (HVA) were markedly elevated. Chromogranin and neuron specific enolase immunostaining of tumor cells was positive, as seen in neuroblastoma. Electron microscopic studies showed cells that were closely packed and connected by occasional cell junctions. The cell cytoplasm contained moderate amounts of filaments and microtubules. Numerous electron dense granules were observed; however, these granules lacked distinct nucleoids and generally reacted strongly for acid phosphatase, indicating a lysosomal rather than a secretory function. Tumor cells contained near-pseudotetraploid chromosomes, with all chromosomes represented at least three times, and chromosome 5 was present in multiples of eight. Clonal structural abnormalities included 2q+ and 5q+ and multiple double minutes. Northern blot analysis revealed both c-myc and N-myc expression; however, N-myc amplification was not demonstrated, and c-myc expression appeared increased, unlike cases of rapidly progressive neuroblastoma. These results suggest that despite biologic similarities to neuroblastoma in catecholamine excretion and some ultrastructural features, molecular genetic abnormalities differ in this comparatively aggressive case of estesioneuroblastoma.

Neuroblastoma presenting as acute monoblastic leukemia

Purpose: We report a 5-year-old boy with stage 4 neuroblastoma initially diagnosed as having acute monoblastie leukemia (FAB M5A. AMoL), based on bone marrow morphology, histochem-istry. immunocytochemistry. immunophenotyping. and cytoge-netics. all consistent with AMoL. The patient also had circulating blasts at diagnosis. After failing initial therapy for AMoL and because of concerns about residual blasts with a clumped appearance in the bone marrow, urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA and N-myc amplification in tumor cells were evaluated and found to be positive, resulting in the diagnosis of neuroblastoma. Abdominal computerized tomography showed a left adrenal mass. A review of 10 reported cases of neuroblastoma with leukemic features showed that seven of them were misdiagnosed as having leukemia, and in six of the seven, the diagnosis of neuroblastoma was made postmortem. Conclusion: Neuroblastoma may be confused with acute leukemia, even with the use of modern techniques.

Postoperative chemotherapy for primary intracranial germ cell tumo

Two children with primary intracranial mixed germ cell tumors are described who were successfully treated by partial resection of the tumor followed by sequential combination chemotherapy without radiation therapy. The chemotherapy consisting of VP-16 and cisplatin alternating with vincristine, methotrexate, and bleomycin resulted in apparent complete response after 6 to 7 months of treatment. Disease-free remission has continued 30-34 months off therapy. A small residual mass in one patient continues to decrease in size on magnetic resonance imaging and is presumed to represent postsurgical change rather than malignant tumor. This report demonstrates that chemotherapy may be effective in primary germ cell tumors of the suprasellar and pineal regions and could be considered for primary treatment instead of radiotherapy.

Terminal deoxynucleotidyl transferase negative acute lymphoblastic leukemia in two offspring of mothers exposed to diethylstilbestrol (DES) in utero.

We report two children with leukemia who were born to diethylstilbestrol (DES)-exposed mothers. The children were 2 and 6 years old at diagnosis and the lymphoblasts expressed the unusual terminal deoxynucleotidyl transferase negative phenotype. Both children completed induction and maintenance therapy and are alive 6 and 4 years from diagnosis. The role of DES as a transplacental carcinogen is reviewed, and a hypothesis for the target cell interaction is proposed.

Clinical, histologic, and genetic features of mesothelioma in a 7-year-old child.

Malignant mesothelioma (MM) is a highly aggressive malignancy that is extremely rare in children. This case report documents a 7‐year‐old male without previous asbestos exposure with peritoneal MM that initially responded to chemotherapy with cisplatin and gemcitabine but ultimately metastasized to his chest. He was diagnosed with MM based on histology, extensive immunohistochemical analyses, and an elevated serum CA‐125 level. Cytogenetics and comparative genomic hybridization (CGH) analysis of his tumor identified a single extra copy number of chromosome 11 with few other changes noted. Pediatr Blood Cancer 2013; 60: 146–148.