IntroductionHox proteins are homeodomain-containing transcription factors (TFs) that play a vital role in establishing body plan during development. In addition to this role in body planning, Hox proteins have been implicated in limb regeneration, wound healing, adipogenesis, and hematopoietic stem cell self-renewal. 1 Hoxa9, in particular, is expressed at high levels in early hematopoietic progenitor cells and promotes stem cell expansion. In contrast, Hoxa9 down-regulation is associated with hematopoietic differentiation. 2,3 In keeping with this role, Hoxa9 knock-out mice show defects in B and T-cell lymphopoiesis and myelopoiesis. 4 HOXA9 has been intensively studied because of its central role in human acute leukemias. [5][6][7][8] Early studies of BXH2 mice, which spontaneously develop acute myeloid leukemia (AML) as a result of endogenous retroviral integration, showed that overexpression of Hoxa9, as a result of integrations at the locus, is one of the most common genetic abnormalities in these leukemias. 9,10 Subsequent gene expression profiling studies showed that HOXA9 is expressed in many AMLs. Of 6817 genes tested, HOXA9 was the single most predictive marker for poor prognosis. 11 Certain subtypes of acute leukemias, particularly those with rearrangements of the mixed lineage leukemia (MLL) gene, show especially high expression of A cluster HOX genes, 5,6,8 which is critical for MLL fusion protein-mediated transformation. 12,13 However, deregulation of Hox expression also appears to play a central role in leukemias without MLL rearrangements, including AMLs associated with the CALM-AF10 translocation, fusions of HOXA9 to the nucleoporin gene NUP98 in a subset of leukemias with the t(7;11), 14,15 overexpression of CDX2 or CDX4 [16][17][18] and identified T-cell acute lymphoblastic leukemia cases with translocations between the TCR␤ and the HOXA9/HOXA10 locus. 19

The use of mouse gene targeting to study molecules important in neural development is oftentimes impaired by early embryonic lethality. In order to address later roles for such molecules, specifically in neural stem cells, we generated transgenic mice that express both the tetracycline-inducible molecule rtTA-M2 and GFP under the control of the neural precursor specific form of nestin. Developmental analysis of these mice demonstrates that GFP expression is exclusive to the neural tube. Adult expression of GFP is seen only in known areas of adult neurogenesis, namely, the subventricular zone and the dentate gyrus. When crossed with a second transgenic mouse (TetOp-Cre) that expresses the Cre recombinase under the control of the tetracycline responsive promotor, we demonstrate temporal induction of Cre in bigenic animals exposed to doxycycline. We further demonstrate the feasibility of this approach by using the ROSA-26 reporter mouse to mediate recombination in neural precursor cells.

Glomangiopericytoma (sinonasal-type hemangiopericytoma) is an uncommon sinonasal neoplasm with a perivascular myoid phenotype. This tumor differs from conventional soft tissue hemangiopericytoma in location, biologic behavior, and histologic features. The proposed cell of origin is a modified perivascular glomuslike myoid cell. Glomangiopericytoma is an indolent tumor that tends to arise in the sinonasal tract of older adults and has a low malignant potential with excellent prognosis after surgical resection. Histologically, this lesion is composed of a diffuse, subepithelial proliferation of bland, uniform, closely packed spindled cells growing in a variety of patterns. A distinctive vascular network composed of variably sized vascular channels, the smaller of which demonstrate perivascular hyalinization, is often present. We report the case of a 48-year-old woman with epistaxis and nasal obstruction who was diagnosed with glomangiopericytoma and discuss the histologic differential diagnosis.

Low-grade fibromyxoid sarcoma (LGFMS) is a rare, typically deep-seated soft tissue neoplasm with deceptively bland cytology and metastatic potential. A t(7;16)(q34;p11) translocation, yielding a FUS/CREB3L2 fusion gene, has been identified in approximately 80%-90% of deep soft tissue LGFMS. Cutaneous fibromyxoid neoplasms occur not infrequently; dermatopathologists rarely consider LGFMS in the differential diagnosis, as this lesion is uncommon in the skin. We identified a group of superficial LGFMS and a spectrum of other cutaneous fibromyxoid neoplasms and performed fluorescence in situ hybridization (FISH) to assess the frequency of FUS rearrangement. FISH for the chromosomal rearrangement of FUS (16p11), using a dual-color, break-apart probe (Abbott Molecular/Vysis, Des Plaines, IL), was performed on formalin-fixed paraffin-embedded tissue sections from superficial LGFMS (n = 6), myxomas (n = 10), and myxofibrosarcoma/myxoid malignant fibrous histiocytomas (myxoid MFH) (n = 5). One hundred nonoverlapping tumor nuclei per case were evaluated for either fused (normal) or split (translocated) signals. Of the LGFMS, 4 of 6 (67%) showed a rearrangement of FUS (range: 72%-80% positive nuclei per 100 nuclei). The other neoplasms within the differential diagnosis were devoid of any rearrangement involving FUS (range: 0%-2% positive nuclei per 100 nuclei). Our observed frequency of FUS rearrangement in superficial LGFMS is consistent with those published in the literature for more deeply seated lesions. When applied to suspicious superficial myxoid or fibromyxoid neoplasms, the FUS FISH probe in formalin-fixed paraffin-embedded tissue can be a useful ancillary technique for diagnosis of this uncommon and deceptively bland tumor.