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.

Mast cell sarcoma in an infant: a case report and review of the literature.

Mast cell diseases comprise a spectrum of disorders including cutaneous mastocytosis, indolent or aggressive systemic variants including leukemia, and unifocal tumor formations such as benign extracutaneous mastocytoma or aggressive mast cell sarcoma (MCS). Many mast cell diseases are associated with aberrancy of c-KIT proto-oncogene resulting in tyrosine kinase activity, typically exhibiting point mutation in codon 816. MCS is an exceedingly rare clinicopathologic entity characterized by a unifocal accumulation of neoplastic mast cells that grow in a locally destructive manner. We report a case in a 2-year-old boy who was initially diagnosed at 8 months of age with atypical cutaneous mastocytoma of the right ear with subsequent aggressive, destructive growth pattern; features that were most consistent with MCS. So far, MCS has been documented in the literature in at least 6 human cases. To the best of our knowledge, our case represents the first MCS in an infant. Thorough multimodal approach with strict follow-up is relevant in appropriately diagnosing this rare entity, particularly in differentiating this lesion from other neoplasms that are more likely to occur in infancy.

Alcohol fat clearing increases lymph node yield after surgery for colorectal cancer.

Lymph node (LN) yield is associated with oncologic outcome in patients who undergo surgery for colorectal adenocarcinoma (CRC). Standards to maximize LN yield have been initiated to enhance treatment of patients with CRC. This study evaluates the impact of a simple alcohol-based preparation protocol on LN yield. Surgical specimens from patients with CRC were prepared using either the alcohol protocol or standard formalin fixation and LN yield was compared. In total, 80 consecutive patients (n = 40 formalin, n = 40 alcohol) were examined. Overall, median LN yield increased from 17 to 29 (P < 0.01) with the alcohol fat clearance protocol. For patients with rectal adenocarcinoma who underwent proctectomy after neoadjuvant chemoradiotherapy, LN yield increased from 15 to 23 (P = 0.02). The frequency of need for additional sampling to achieve a minimum 12 LN count was also reduced. Initiation of a standardized alcohol fat-clearing protocol increased LN yield after surgery for CRC. This simple, cost-effective measure may improve the efficiency of LN assessment and accurate staging, which may impact oncologic outcomes.

Occult hematologic malignancy in routine tonsillectomy specimens: a single institutional experience and review of the literature.

OBJECTIVES: Handling of tonsillectomy specimens often includes gross and histologic examination. The published incidence of occult malignancy in benign-appearing tonsils is vanishingly rare, and consequently some propose omitting histologic analysis in young patients without clinical risk factors for malignancy or grossly suspicious features. METHODS: At our institution, an occult Burkitt lymphoma in a grossly benign-appearing tonsil from an otherwise healthy 5-year-old prompted review of our cases. We retrospectively reviewed tonsillectomy findings over a 5-year period, excluding patients with known lymphoma or head and neck malignancies. A total of 740 patients were identified. All cases underwent gross and histologic examination. RESULTS: Four additional malignancies were diagnosed, including a clinically unsuspected lymphoma in a 14-year-old patient. In our experience, although most tonsillar malignancies present with suspicious clinical or gross findings, occult malignancies do occur. CONCLUSIONS: Recognition of these occult findings may facilitate early diagnosis and treatment; thus pathologic study of these specimens may still be justified.

Barrett's esophagus: A review of diagnostic criteria, clinical surveillance practices and new developments.

Barrett's esophagus is defined by metaplastic glandular changes to the distal esophagus and is linked to an increased risk of esophageal adenocarcinoma. Controversy exists whether the definition should be limited to intestinal type glands with goblet cells or should be expanded to include non-goblet cell columnar epithelium. Barrett's esophagus may be asymptomatic in a large proportion of the population but screening should be considered for those with certain clinical findings. The diagnosis of Barrett's should be based on the combination of careful endoscopic evaluation and histologic review of the biopsy material. Continued surveillance biopsies may be necessary in cases of indeterminate or low grade dysplasia. Clinical follow-up of patients with high grade dysplasia should be tailored to the individual patient. Development of newer endoscopy techniques including chemoendoscopy, chromoendoscopy and use of biomarkers on frozen tissue have shown some promise of identifying patients at risk for malignancy.

A folding pattern that is stable to thermal cycling is achieved by long term storage of recombinant human beta-casein with four extra N-terminals amino-acid residues at -20 degrees C.

Studies have followed the turbidity (OD400 nm) of beta-casein (CN) as temperature (T) increased from 4 to 37 degrees C. Native non-phosphorylated beta-CN showed a turbidity increase above 25 degrees C and precipitated at about 22 degrees C in 5mM Ca+2. These patterns were reproducible upon T-cycling while those of recombinant beta-CN proteins are not. Here, a wild-type recombinant that was thermally stable after being frozen in solution and stored at -20 degrees C for a prolonged period of time was denatured with guanidine HCl and refolded by dialysis against buffer. This protein was again not stable to T-cycling. A recombinant mutant with four extra N-terminal amino acids was very stable to T-cycling, both with and without 5mM Ca+2. However, it was still much different than the native protein. These results indicate that there are probably many energy minima for this protein and emphasize the possibility of "chaperon-like" conditions for proper folding of human beta-CN.