Trends in Bone Marrow Sampling and Core Biopsy Specimen Adequacy in the United States and Canada: A Multicenter Study.

OBJECTIVES: To assess bone marrow (BM) sampling in academic medical centers. METHODS: Data from 6,374 BM samples obtained in 32 centers in 2001 and 2011, including core length (CL), were analyzed. RESULTS: BM included a biopsy (BMB; 93%) specimen, aspirate (BMA; 92%) specimen, or both (83%). The median (SD) CL was 12 (8.5) mm, and evaluable marrow was 9 (7.6) mm. Tissue contraction due to processing was 15%. BMB specimens were longer in adults younger than 60 years, men, and bilateral, staging, and baseline samples. Only 4% of BMB and 2% of BMB/BMA samples were deemed inadequate for diagnosis. BM for plasma cell dyscrasias, nonphysician operators, and ancillary studies usage increased, while bilateral sampling decreased over the decade. BM-related quality assurance programs are infrequent. CONCLUSIONS: CL is shorter than recommended and varies with patient age and sex, clinical circumstances, and center experience. While pathologists render diagnoses on most cases irrespective of CL, BMB yield improvement is desirable.

Next generation sequencing of progressive colorectal liver metastases after portal vein embolization.

Portal vein embolization (PVE) can be required to stimulate liver regeneration before hepatectomy for colorectal liver metastasis (CRCLM), however PVE may also trigger CRCLM progression in patients initially exhibiting chemotherapy response. Using RNA-seq, we aimed to determine the molecular networks involved in metastatic progression in this context. A prospective study including all CRCLM patients undergoing PVE prior to hepatectomy was conducted. Paired biopsies of metastatic lesions were obtained prior to and after PVE and total RNA was isolated and used to prepare Illumina rRNA-depleted TruSeq stranded cDNA libraries for HiSeq 100 bp paired-end sequencing. Patients were classified with progression of disease (PDPVE) or stable disease (SDPVE) post-PVE using 3D-CT tumor volumetric analysis. RESULTS: Twenty patients were included, 13 (65.0%) in the PDPVE group (median 58.0% (18.6-234.3) increase in tumor volume) and 7 (35.0%) in the SDPVE group exhibiting continuous chemotherapy response (median -14.3% (-40.8 to -2.8) decrease in tumor volume) (p < 0.0001). Our results showed that progressive CRCLM after PVE undergo gene expression changes that indicate activation of core cancer pathways (IL-17 (p = 5.94 × 10-03), PI3K (p = 8.71 × 10-03), IL6 and IGF-1 signaling pathways), consistent with changes driven by cytokines and growth factors. Differential expression analysis in a paired model of progression (EdgeR, DeSeq) identified significantly dysregulated genes in the PDPVE group (FOS, FOSB, RAB20, IRS2). CONCLUSION: Differentially expressed genes and pathways with known links to cancer and metastasis were identified post-PVE in patients with disease progression. Highlighting these molecular changes is a crucial first step towards development of targeted therapeutic strategies that may mitigate the effects of PVE on tumor growth.

Decreased PCSK9 expression in human hepatocellular carcinoma.

BACKGROUND: The management of hepatocellular carcinoma (HCC) is limited by the lack of adequate screening biomarkers and chemotherapy. In response, there has been much interest in tumor metabolism as a therapeutic target. PCSK9 stimulates internalization of the LDL-receptor, decreases cholesterol uptake into hepatocytes and affects liver regeneration. Thus, we investigated whether PCSK9 expression is altered in HCC, influencing its ability to harness cholesterol metabolism. METHODS: Thirty-nine patients undergoing partial hepatectomy or liver transplantation for HCC were consented for use of HCC tissue to construct a tissue microarray (TMA). The TMA was immunostained for PCSK9. Imagescope software was used to objectively determine staining, and assess for pathological and clinical correlations. PCSK9 and LDL receptor mRNA levels in flash-frozen HCC and adjacent liver tissue were determined by quantitative RT-PCR. Serum PCSK9 levels were determined by ELISA. RESULTS: By immunohistochemistry, there was significantly lower expression of PCSK9 in HCC as compared to adjacent cirrhosis (p-value < 0.0001, wilcoxon signed-rank test). Significantly greater staining of PCSK9 was present in cirrhosis compared to HCC (p value <0.0001), and positivity (percentage of positive cells) was significantly greater in cirrhosis compared to HCC (p-value < 0.0001). Conversely, significantly higher expression of LDL-R was present in HCC as compared to the adjacent cirrhosis (p-value < 0.0001). There was no significant correlation of PCSK9 staining with grade of tumor, but there were significant correlations between PCSK9 staining and stage of fibrosis, according to spearman correlation test. PCSK9 mRNA levels were relatively less abundant within HCC compared to adjacent liver tissue (p-value =0.08) and normal control tissue (p-value =0.02). In contrast, serum PCSK9 levels were significantly increased among patients with HCC compared to those with chronic liver disease without HCC (p-value =0.029). LDL receptor mRNA was consistantly greater in HCC when compared to normal control tissue (p-value = 0.06) and, in general, was significantly greater in HCC when compared to adjacent liver (p-value = 0.04). CONCLUSIONS: The decreased expression of PCSK9 and conversely increased LDL-R expression in HCC suggests that HCC modulates its local microenvironment to enable a constant energy supply. Larger-scale studies should be conducted to determine whether PCSK9 could be a therapeutic target for HCC.

Hepatic ALECT-2 amyloidosis causing portal hypertension and recurrent variceal bleeding: a case report and review of the literature.

OBJECTIVES: To examine laser microdissection and mass spectrometry (LMD-MS), which has emerged as a new tool to aid in typing amyloid proteins. RESULTS: ALECT-2 is a potential cause of hepatic amyloidosis best detected by LMD-MS. METHODS: One of the more recently reported proteins is ALECT-2 (leukocyte cell-derived chemotaxin 2) amyloid, found in renal specimens of Hispanic patients. Here we report the first case of hepatic ALECT-2 amyloidosis diagnosed by LMD-MS from a liver biopsy specimen of a 52-year-old Hispanic man and causing portal hypertension with recurrent esophageal variceal bleeding. CONCLUSIONS: ALECT-2 can cause amyloidosis in organs other than the kidneys. It should be strongly considered in Hispanic patients and in those with a globular pattern of amyloid deposition. The incidence of ALECT-2 amyloidosis is likely underreported.

Amyloidosis in FDG-avid lymph nodes.

Amyloidosis in lymph node that is FDG-avid is an unusual diagnosis. FDG PET/CT showed the presence of multifocal lymphadenopathy mainly axillary with a mesenteric mass. Surgical lymph node biopsy with histological examination confirmed the diagnosis of amyloidosis in a 64-year-old woman with an initial left axillary pain. Amyloidosis should be considered on the differential diagnosis for a FDG-avid lymphadenopathy. Other differential diagnosis usually includes malignancy such as lymphoma or metastatic disease, infection, or sterile inflammation.

Penicillium marneffei infection in an immunocompromised traveler: a case report and literature review.

Penicillium marneffei has emerged as an important opportunistic pathogen in Southeast Asia during the human immunodeficiency virus (HIV) epidemic. We report a case of disseminated P. marneffei in a person with previously undiagnosed acquired immunodeficiency syndrome (AIDS) who traveled to Southeast Asia, illustrating the importance of considering this diagnosis in immunocompromised travelers.

Epithelioid angiosarcoma involving the lungs.

Diffuse lung involvement by metastatic tumor from an unknown primary site often constitutes a diagnostic dilemma. Although cytologic features and pattern of metastatic spread can guide in narrowing the list of possible primary neoplasms, immunohistochemistry remains pivotal in determining the phenotype of metastatic disease. We report a case with extensive involvement of lung parenchyma by a metastatic epithelioid neoplasm exhibiting a variety of distinctive patterns with a predominance of intra-arterial and lymphangitic spread. Immunohistochemical studies showed no evidence of epithelial, melanocytic, or lymphoid differentiation. The neoplastic cells were strongly positive for vimentin and CD31 but negative for CD34 and factor VIIIR:Ag. Electron microscopy of formalin-fixed tissue revealed multiple Weibel-Palade bodies and pinocytosis, supporting the diagnosis of epithelioid angiosarcoma. Doppler studies performed after pathologic diagnosis was rendered demonstrated 2 discrete hypoechoic masses within the medial aspect of the left proximal calf musculature, suggestive of solid soft tissue neoplasm-a possible source of pulmonary metastatic disease.