De novo acute myeloid leukemia with 20-29% blasts is less aggressive than acute myeloid leukemia with ≥30% blasts in older adults: a Bone Marrow Pathology Group study.

It is controversial whether acute myeloid leukemia (AML) patients with 20-29% bone marrow (BM) blasts, formerly referred to as refractory anemia with excess blasts in transformation (RAEBT), should be considered AML or myelodysplastic syndrome (MDS) for the purposes of treatment and prognostication. We retrospectively studied 571 de novo AML in patients aged >50 years, including 142 RAEBT and 429 with ≥30% blasts (AML30), as well as 151 patients with 10-19% BM blasts (RAEB2). RAEBT patients were older and had lower white blood count, but higher hemoglobin, platelet count, and karyotype risk scores compared to AML30, while these features were similar to RAEB2. FLT3 and NPM1 mutations and monocytic morphology occurred more commonly in AML30 than in RAEBT. RAEBT patients were treated less often with induction therapy than AML30, whereas allogeneic stem cell transplant frequency was similar. The median and 4-year OS of RAEBT patients were longer than those of AML30 patients (20.5 vs 12.0 months and 28.6% vs 20.4%, respectively, P = 0.003); this difference in OS was manifested in patients in the intermediate UKMRC karyotype risk group, whereas OS of RAEBT patients and AML30 patients in the adverse karyotype risk group were not significantly different. Multivariable analysis showed that RAEBT (P < 0.0001), hemoglobin (P = 0.005), UKMRC karyotype risk group (P = 0.002), normal BM karyotype (P = 0.004), treatment with induction therapy (P < 0.0001), and stem cell transplant (P < 0.0001) were associated with longer OS. Our findings favor considering de novo RAEBT as a favorable prognostic subgroup of AML.

An infant with combination gene mutations for Monogenic Diabetes of Youth (MODY) 2 and 4, presenting with Diabetes Mellitus Requiring Insulin (DMRI) at 8 months of age.

Monogenic Diabetes of Youth (MODY) is an autosomal dominant form of diabetes. [Fajans SS, et al. NEJM 2001: 345: 971-980.] There are at least six different types of MODY, all of which involve a loss of function gene mutation that results in diminished insulin production. MODY2 results from a mutation in the glucokinase gene (GCK), which decreases enzyme activity. MODY4 results from a mutation in the insulin promoter factor-1 (IPF-1) gene, a transcription factor which regulates the transcription of insulin. [Sperling M, et al. NEJM 2006: 355: 507-510.] TJ presented at 8 months of age with diabetes mellitus requiring insulin (DMRI) with negative islet autoantibodies. She had a prolonged honeymoon period, as evidenced by her insulin requirement of 0.5 units/kg/day at three years of age. Genetic testing showed combination MODY2 (c.1019+18G >A) and MODY4 (c.226G>A) gene mutations. The father was homozygous for MODY2 and the mother was heterozygous for MODY4. [Athena Diagnostics Evaluations "2007 # 839 - Monogenic Diabetes (MODY) Evaluation for the patient, the patient's father, and the patient's mother] Neither parent had diabetes mellitus. The clinical course and negative islet autoantibodies support that the combination of benign MODY2 and MODY4 gene mutations in the parents resulted in DMRI in TJ.

Papillary thyroid cancer in struma testis with malignant transformation in the lung associated with trisomy 17 successfully treated with total thyroidectomy and radioiodine ablation.

BACKGROUND: Struma testis is a rare entity, and there are only few reports on the malignant transformation of a testicular teratoma to papillary thyroid carcinoma in the literature. In this report, we describe the malignant transformation of struma testis with distant lung metastasis associated with trisomy 17 and a coexisting papillary microcarcinoma in the thyroid. CASE REPORT: A 56-year-old man presented after a left orchiectomy for an undescended left testicle. Pathologic examination identified a monodermal teratoma composed of thyroid parenchyma and associated with a 1.7-cm papillary thyroid carcinoma. Further evaluation showed a pulmonary mass on a chest CT scan. Total thyroidectomy revealed a 0.5-mm focus of papillary thyroid cancer, and removal of the lung mass confirmed metastatic papillary thyroid cancer. Array-comparative genomic hybridization of both tumors showed trisomy 17 in the struma testes and the lung metastasis. The patient responded well to radioactive iodine ablation and has no evidence of cancer 3 years later. CONCLUSION: To our knowledge, this is the first case of papillary thyroid cancer in struma testes metastatic to the lung. It highlights the difficulties in treating these patients. Surgery to remove cancer foci, followed by radioactive iodine ablation, resulted in an excellent response in our patient. Interestingly, trisomy 17, which has so far been observed only in noninvasive thyroid nodules, was associated with pulmonary metastasis in our patient.

A Novel del(20q) in Aggressive Nodal Marginal Zone Lymphoma.

This is a case report of a previously undescribed 20q chromosomal deletion (del(20q)) in marginal zone lymphoma (MZL). A 54-year-old Caucasian male presented with an enlarging neck mass and multiple violaceous skin nodules over his chest. Biopsy of the neck mass and cervical lymph nodes revealed MZL. Cytogenetic evaluation of both lymph node and bone marrow tissue revealed del(20q). This was an unexpected finding, as del(20q) is associated with myelodysplastic syndromes and myeloproliferative neoplasms and rarely seen in diffuse large B-cell lymphoma, follicular lymphoma, and T-cell lymphoma, but has not previously been described in MZL. We describe the case presentation and histologic findings and discuss the significance of this novel finding.

Deceptively benign low-grade fibromyxoid sarcoma: array-comparative genomic hybridization decodes the diagnosis.

Low-grade fibromyxoid sarcoma (previously known as Evans tumor) is a rare soft tissue neoplasm characterized by a deceptively bland appearance despite the potential for late metastasis or recurrence. We describe a 13-year-old patient with a popliteal fossa mass initially thought to be benign that, because of array-comparative genomic hybridization findings and subsequent immunohistochemistry, was diagnosed as low-grade fibromyxoid sarcoma. The array-comparative genomic hybridization demonstrated a loss of 11p11.2p15.5 and a gain of 16p11.2p13.3 with breakpoints involving the CREB3L1 (cAMP responsive element-binding protein 3-like 1) and FUS (fused in sarcoma) genes, respectively. Subsequent fluorescence in situ hybridization analysis of a dual-labeled break-apart FUS probe on interphase cells was positive. Our case highlights the importance of using genetic information obtained via array-comparative genomic hybridization to classify accurately pediatric soft tissue tumors.

Skin metastases in non-small cell lung cancer.

Skin metastasis associated with lung cancer is an uncommon manifestation and usually portends an aggressive clinical course. It can be either synchronous with the underlying malignancy or be the sign of recurrence. Solitary metastases can be treated with surgical resection or radiation therapy, but multiple lesions are usually treated with palliative chemotherapy. With standard platinum-based doublet regimens, treatment results are usually poor. With the advent of newer agents like pemetrexed, bevacizumab and erlotinib, perhaps results may improve with ongoing clinical trials.