Silvia Taccogna

Percutaneous Laser Ablation in the Treatment of Hepatocellular Carcinoma with Small Tumors: Analysis of Factors Affecting the Achievement of Tumor Necrosis

PURPOSE To identify the factors that affect the achievement of tumor necrosis with percutaneous laser ablation (PLA) in patients with hepatocellular carcinoma (HCC) and tumor size no larger than 4.0 cm. MATERIALS AND METHODS Ultrasound-guided biopsy results were retrospectively studied in 99 lesions (range, 0.5-4.0 cm; mean, 2.7 cm) from 82 patients (44 men, 38 women; age range, 50-80 years; median, 68 y) who had undergone PLA. RESULTS Complete tumor ablation was obtained in 90 lesions (90.9%). Of the nine cases in which complete tumor necrosis was not achieved, six had tumors located in sites that did not allow the optimal placement of fibers, and five of these had a tumor diameter greater than 3 cm. Early discontinuation of PLA as a result of decompensation of liver cirrhosis was the reason for not achieving a complete tumor ablation in three other cases. There was a clear relationship between the energy delivered and the volume of necrosis achieved (r = 0.56; P < .001) regardless of the initial size of HCC tumors. The number of illuminations required, and consequently the amount of energy delivered, was also affected by tumor location. In fact, lesions adjacent to large vessels (> or = 3 mm) required a greater number of illuminations than the other lesions to achieve complete ablation (2.9 +/- 1.4 vs 2.3 +/- 0.9; P = .043). The eight cases with undifferentiated histology required more illuminations than the cases with other histologic types (3.4 +/- 0.9 vs 2.2 +/- 0.9; P < .001). However, these cases were located in sites that did not allow the optimal placement of fibers, therefore requiring multiple treatments. CONCLUSION PLA is a highly effective treatment in HCC with a tumor size of 4.0 cm or smaller. In this setting, two variables, tumor size and tumor location, affect the achievement of complete tumor ablation and the number of treatments required to obtain tumor necrosis.

The use of core needle biopsy as first-line in diagnosis of thyroid nodules reduces false negative and inconclusive data reported by fine-needle aspiration

BackgroundThe reported reliability of core needle biopsy (CNB) is high in assessing thyroid nodules after inconclusive fine-needle aspiration (FNA) attempts. However, first-line use of CNB for nodules considered at risk by ultrasonography (US) has yet to be studied. The aim of this study were: 1) to evaluate the potential merit of using CNB first-line instead of conventional FNA in thyroid nodules with suspicious ultrasonographic features; 2) to compare CNB and FNA as a first-line diagnostic procedure in thyroid lesions at higher risk of cancer.MethodsSeventy-seven patients with a suspicious-appearing, recently discovered solid thyroid nodule were initially enrolled as study participants. No patients had undergone prior thyroid fine-needle aspiration/biopsy. Based on study design, all patients were proposed to undergo CNB as first-line diagnostic aspiration, while those patients refusing to do so underwent conventional FNA.ResultsFive patients refused the study, and a total of 31 and 41 thyroid nodules were subjected to CNB and FNA, respectively. At follow-up, the overall rate of malignancy was of 80% (CNB, 77%; FNA, 83%). However, the diagnostic accuracy of CNB (97%) was significantly (P < 0.05) higher than that of FNA (78%). In one benign lesion, CNB was inconclusive. Four (12%) of the 34 cancers of the FNA group were not initially diagnosed because of false negative (N = 1), indeterminate (N = 2) or not adequate (N = 1) samples.ConclusionsCNB can reduce the false negative and inconclusive results of conventional FNA and should be considered a first-line method in assessing solid thyroid nodules at high risk of malignancy.

Immunohistochemistry for BRAF(V600E) Antibody VE1 Performed in Core Needle Biopsy Samples Identifies Mutated Papillary Thyroid Cancers

BRAF(V600E) is the most frequent genetic mutation in papillary thyroid cancer (PTC) and has been reported as an independent predictor of poor prognosis of these patients. Current guidelines do not recommend the use of BRAF(V600E) mutational analysis on cytologic specimens from fine needle aspiration due to several reasons. Recently, immunohistochemistry using VE1, a mouse anti-human BRAF(V600E) antibody, has been reported as a highly reliable technique in detecting BRAF-mutated thyroid and nonthyroid cancers. The aim of this study was to test the reliability of VE1 immunohistochemistry on microhistologic samples from core needle biopsy (CNB) in identifying BRAF-mutated PTC. A series of 30 nodules (size ranging from 7 to 22 mm) from 30 patients who underwent surgery following CNB were included in the study. All these lesions had had inconclusive cytology. In all cases, both VE1 and BRAF(V600E) genotypes were evaluated. After surgery, final histology demonstrated 21 cancers and 9 benign lesions. CNB correctly diagnosed 20/20 PTC and 5/5 adenomatous nodules. One follicular thyroid cancer and 4 benign lesions were assessed at CNB as uncertain follicular neoplasm. VE1 immunohistochemistry revealed 8 mutated PTC and 22 negative cases. A 100% agreement was found when positive and negative VE1 results were compared with BRAF mutational status. These data are the first demonstration that VE1 immunohistochemistry performed on thyroid CNB samples perfectly matches with genetic analysis of BRAF status. Thus, VE1 antibody can be used on thyroid microhistologic specimens to detect BRAF(V600E)-mutated PTC before surgery.

Utility of HBME-1 immunostaining in serous effusions.

Utility of HBME‐1 immunostaining in serous effusions

Primary Gastric Plasmacytoma and Helicobacter pylori Infection

A 65-year-old woman presented in April 2007 with a 3-month history of abdominal discomfort and occasional epigastric pain. The patient’s past medical history was otherwise unremarkable. Physical examination was significant only for mild epigastric tenderness to deep palpation without rebound or guarding. Both the complete blood cell count and routine blood chemistry did not show any significant abnormality. An upper endoscopy revealed bulging of the gastric wall and loss of gastric folds, with hyperemic and friable gastric mucosa from the antrum to the posterior side of midbody (Fig 1). Multiple biopsies from the lesion showed dense infiltration of atypical plasma cells in the gastric mucosa, with no demonstration of centrocyte-like cells or reactive follicles (Fig 2A, hematoxylin and eosin stain). Immunostaining with an anticytokeratine antibody (CKMNF116) highlighted the absence of lymphoepithelial lesions (ie, the glandular epithelium was not infiltrated by the malignancy; Fig 2B). Plasma cells stained positively for CD-79a, CD138 (Fig 3A), immunoglobulin (Ig) G, lambda chain (Fig 3B), and the bcl-6 oncogene product, but negative for CD-3, CD-20, CD-45, IgA, IgM, kappa chain, and bcl-2 protein. These findings were consistent with the diagnosis of plasmacytoma. Helicobacter pylori (H pylori) was identified on Giemsa-stained sections (Fig 4, arrows). The Updated Sydney System grading of H pylori infection and inflammation was mild to moderate. Following the pathology report, a number of additional investigations were undertaken. No monoclonal component was identified in serum or urine immunofixation tests. Whole-body computed tomography, as well as skeletal radiological survey, did not show the presence of any additional tumor mass or bone lesions. Bone marrow aspirates and trephine bone marrow biopsy specimens taken from the posterior iliac crest showed a normal marrow with a proportion of polyclonal plasma cells less than 5% of the total marrow nucleated cells. Seminested polymerase chain reaction amplification revealed clonal rearrangement (distinct single band) of immunoglobulin heavy chains using primers for the framework region 2A (FR2A)/variable low joining heavy region (VLJH) region in samples from the gastric biopsy (Fig 5), but not from the bone marrow biopsy. Finally, Western blot analysis revealed the presence of antibodies against the cytotoxicity-associated gene A product (CagA) of H pylori (Fig 6). The patient received a 1-week triple therapy regimen consisting of lansoprazole 30 mg twice a day, amoxicillin 1 g twice a day, and clarithromycin 500 mg. A new upper gastrointestinal endoscopy performed 3 months after the cessation of treatment showed the complete disappearance of the tumor. Multiple biopsies were taken from the entire stomach, none of which showed plasmacytic infiltration or H pylori. Polymerase chain reaction analysis also showed regression of the abnormal clone. No relapse was documented endoscopically and histologically 14 months after the initial diagnosis of primary gastric plasmacytoma. Primary extramedullary plasmacytomas account for approximately 4% of all plasma cell neoplasms. They have been described in any soft tissue, most frequently in the upper respiratory tract, and are defined by lack of evidence of bone marrow involvement. Gastric plasmacytoma is rare and constitutes in turn less than 5% of these tumors. Accordingly, the literature about this entity consists of anecdotal reports or small case series. This entity is usually localized and frequently pursues an indolent clinical course, but has a tendency for local recurrence and may rarely progress to overt multiple myeloma. The differential diagnosis includes nonHodgkin’s lymphomas with plasmacytic differentiation such as lymphoplasmacytic lymphoma, follicular lymphoma, monocytoid B-cell lymphoma, and, particularly, mucosa-associated lymphoid tissue (MALT) lymphomas. Up to 30% of patients with MALT lymphoma present plasmacytic differentiation, a feature that is especially prominent in a rare type of MALT lymphoma known as immunoproliferative small intestinal disease. Other than morphologic criteria, including the absence of centrocyte-like cells, reactive follicles, or lymphoepithelial lesions; the expression of CD138; and the lack of B-lymphocyte antigens (such as CD20); are helpful in differentiating gastric plasmacytoma from MALT lymphoma. Analysis of the published data indicates that surgical treatment or irradiation, with or without chemotherapy, has been the predominant therapeutic approach. H pylori is a Gram-negative spiral microaerophilic bacterium that colonizes the human stomach of at least half of the world’s population. A causative association between H pylori infection and gastric tumors, specifically adenocarcinoma and MALT lymphoma, has been established by epidemiologic, biologic, and molecular genetic studies. The link Fig 1. JOURNAL OF CLINICAL ONCOLOGY D I A G N O S I S I N O N C O L O G Y VOLUME 27 NUMBER 1 JANUARY 1 2009

Analysis of differential therapeutic strategies for primary breast lymphoma: two case reports

Primary breast lymphoma (PBL) is a rare form of extranodal non-Hodgkin’s lymphoma (NHL), whose own specific biological characteristics still need to be fully defined. No significant prognostic factor has been found and the optimal therapeutic strategy is uncertain. However, an intensified systemic therapy has been advocated to prevent relapse, even in patients who show a complete response to local treatment. We report two cases of primary diffuse large B-cell breast lymphoma, review the literature about this topic, and discuss treatment options. We conclude that differential therapeutic strategies based on the risk of relapse associated with the International Prognostic Index (IPI) are a reasonable way to approach PBL, and can avoid undue toxicity deriving from treatment.

Kaposi sarcoma of the stomach: a case report

A 60-year-old man presented with persistent dysphagia and weight loss of 2-months duration. An upper GI endoscopy revealed mycotic oesophagitis and chronic gastritis with two ulcers of the gastric body and antrum. Repeat endoscopy was performed after medical treatment failed, and histological examination on new biopsy samples led to a diagnosis of Kaposi sarcoma of the stomach. HIV infection was not known at this time; however, the patient was tested after the diagnosis of Kaposi sarcoma was made and found to be HIV positive. An adequate biopsy sampling was required for histological diagnosis and the use of immunohistochemical markers, especially human herpesvirus 8 (HHV8) antibodies, supplied valid diagnostic support. This case underlines the importance of an accurate evaluation of vascular proliferation in gastrointestinal biopsies even in patients without clinical evidence of HIV-related pathology.

Predictive Value of Malignancy of Thyroid Nodule Ultrasound Classification Systems: A Prospective Study

Context British Thyroid Association (BTA), American Thyroid Association (ATA), and American Association of Clinical Endocrinologists (AACE/ACE/AME) recommend for thyroid nodules an ultrasound (US)-based stratification of risk of malignancy. Aim of our study was to assess the diagnostic accuracy of US classification systems and their reliability for indication to fine-needle aspiration (FNA). Design Prospective study on 987 thyroid nodules consecutively referred for FNA. US images were independently reviewed by four experts for assignment of malignancy risk. Cytologically benign nodules had confirmation with a second FNA, whereas Bethesda class IV, V, and VI nodules were operated upon. Class III nodules had surgery or follow-up on the basis of clinical, immunocytochemical, and US features. Results BTA: Malignancy rate was 2.8% in benign, 10.0% in indeterminate, 51.3% in suspicion, and 80.9% in malignant US class. Sensitivity was 0.74, specificity was 0.92, and accuracy was 0.89. ATA: Malignancy rate was 0.0% in benign, 2.2% in very low suspicion, 3.0% in low suspicion, 5.8% in intermediate, and 55.0% in high suspicion US class. Sensitivity was 0.81, specificity was 0.87, and accuracy was 0.86. AACE/ACE/AME: Malignancy rate was 1.1% in low-risk, 4.4% in intermediate-risk, and 54.9% in high-risk US class. Sensitivity was 0.82, specificity was 0.87, and accuracy was 0.86. K correlation coefficient was 78.9%, 76.9%, and 82.0% for BTA, ATA, and AACE/ACE/AME classifications. Conclusions Classification systems had elevated predictive value of malignancy in high-risk classes. ATA and AACE/ACE/AME systems were effective for ruling out indication to FNA in low-US-risk nodules. A similar diagnostic accuracy and a substantial interobserver agreement was provided by the three- and the five-category classifications.

Phenotypic changes of the thyrocyte membrane in papillary thyroid carcinoma. A three-dimensional study

Aim of the study was to assess the presence of structural changes in the complex carbohydrate chains of thyroid epithelia undergoing neoplastic transformation. We investigated thyroid cells from neoplastic lesions using a panel of lectins with specific affinity for distinct carbohydrate residues. Sixty samples of thyroid tissue, including normal, hyperplastic and neoplastic lesions were obtained from surgical specimens and blindly evaluated with lectin stains. Confocal microscopy was used to obtain three-dimensional (3-D) images of the samples with a positive reaction. Wheat germ agglutinin (WGA) was consistently positive on the apical membrane of papillary thyroid carcinomas (PTC), was weakly expressed in follicular carcinomas (FC) and resulted negative in normal thyrocytes and in benign conditions. The 3-D microscopy model showed that the WGA staining pattern in light microscopy corresponds to a continuous layer on the luminal surface of both papillary and tubular structures of PTC cells. The other lectins under evaluation did not provide any significant result. In conclusion, in PTC the apical border of thyrocytes showed a strong, specific and consistent staining with WGA. These findings may be related to a modified interaction of thyroglobulin molecule with thyroid cell membrane and with the expression of molecules that are involved in the process of tumorigenesis and tumor progression.