Madeleine Pfaltz

Is there a role for positron emission tomography with 18F-fluorodeoxyglucose in the initial staging of nodal negative oral and oropharyngeal squamous cell carcinoma

The aim of our study was to assess the value of positron emission tomography (PET) with 18F‐fluorodeoxyglucose (FDG) for the staging of clinically nodal negative necks in oral and oropharyngeal squamous cell carcinoma (SCC) using sentinel lymph node (SLN) biopsy and elective neck dissection (END) as “gold standard” for comparison.

Sentinel lymph node evaluation in squamous cell carcinoma of the head and neck

OBJECTIVE: The aim of our study was to assess the feasibility of sentinel lymph node (SLN) radiolocalization in N0 neck in squamous cell head and neck carcinoma and its predictive value for occult metastasis. Study Design: Nineteen patients of an open prospective trial. SETTING: After peritumoral injection of a 99m Tc labeled radiocolloid, the SLN was localized preoperatively by lymphoscintigraphy and intraoperatively through the intact skin by a hand-held gamma-probe. The histology of the SLN and the nodes of the elective neck dissection were compared. RESULTS: Localization of the SLN by lymphoscintigraphy was possible in 18 of 19, and with the handheld gamma-probe in all 19 patients. Six SLN revealed occult metastatic disease. No skip metastasis were found in the 13 neck specimen with negative SLN. CONCLUSION: SLN evaluation in N0 neck in squamous cell carcinoma of the head and neck is accurately feasible and seems to adequately predict the presence of occult metastasis.

Combined comparative genomic hybridization and genomic microarray for detection of gene amplifications in pulmonary artery intimal sarcomas and adrenocortical tumors

Identification of gene amplifications in human tumors is important for the understanding of tumorigenesis and may lead to discovery of diagnostic and prognostic markers. In this study, we used a microarray‐based comparative genomic hybridization (CGH) technique, combined with conventional CGH, to identify gene amplifications in 43 tumors including eight pulmonary artery intimal sarcomas and 35 adrenocortical tumors. Conventional CGH revealed gains or amplifications of 12q13–q15 in six sarcomas and in two adrenocortical carcinomas. Using microarrays, we demonstrated that, among genes located on 12q13–q15, SAS/CDK4 were amplified in six sarcomas, and MDM2 and GLI in five and four sarcomas, respectively. The two adrenocortical tumors showed coamplifications of SAS/CDK4 and MDM2. Furthermore, PDGFRA (located on 4q12) amplification was identified in five sarcomas. Our data demonstrate: (1) amplifications of SAS/CDK4, MDM2, GLI, and PDGFRA are strongly associated with the tumorigenesis of pulmonary artery intimal sarcomas, whereas SAS/CDK4 and MDM2 coamplification may contribute to the progression of adrenocortical tumors; (2) microarray‐based CGH is a useful tool for simultaneous detection of multiple gene amplifications, with a high sensitivity and resolution compared to that of conventional CGH.

Histopathological features of occult metastasis detected by sentinel lymph node biopsy in oral and oropharyngeal squamous cell carcinoma.

Objectives Sentinel lymph node biopsy has been introduced for head and neck cancer with promising results. Research in breast cancer has revealed different histopathological features of occult lymph node metastasis with possibly different clinical and prognostic implications. The aim of the study was to evaluate the histopathological features of occult metastasis detected by sentinel lymph node in oral and oropharyngeal squamous cell carcinoma.

Mixed medullary and follicular carcinoma of the thyroid

We report a case of medullary carcinoma of the thyroid which on light microscopy showed not only the well known arrangement of cells in sheets and nests but also unequivocal follicular structures. These follicular structures are present both in the primary tumor and in lymph node metastases. Immunohistochemical investigations revealed that the cells lining the follicles produce thyroglobulin, whereas the remaining tumor tissue is positive for calcitonin and carcinoembrionic antigen. This case represents a medullary carcinoma of the thyroid with an atypical pattern consisting of both thyroglobulin and calcitonin producing cells.

Inflammatory Monocytes Are a Reservoir for Merkel Cell Polyomavirus

Merkel cell polyomavirus (MCPyV) is a recently discovered virus that is implicated in the oncogenesis of Merkel cell carcinoma (MCC). The route of dissemination and the reservoir(s) of MCPyV within the human body have not yet been identified. In this study we describe two patients with multiple MCPyV-positive inflammatory and neoplastic skin lesions at different anatomic sites. Patient 1 was suffering from psoriasis for many years and was diagnosed with MCC 7 years before this study. Patient 2 had developed numerous non-melanoma skin cancer lesions under post-transplant immunosuppression. In both patients, MCPyV DNA was detected in whole blood and in urine using PCR and direct sequencing of PCR products. When we analyzed different blood compartments, we found MCPyV exclusively in cell-free serum and in blood monocytes, but not in lymphocytes or granulocytes. Upon separate analysis of resident (CD14(lo)CD16(+)) and inflammatory (CD14(+)CD16(-)) monocytes, we detected MCPyV exclusively in inflammatory, but not in resident monocytes. Our findings raise the possibility that MCPyV persists in inflammatory monocytes and spreads along the migration routes of inflammatory monocytes. This points to intervention strategies to contain MCPyV. Moreover, blood or urine tests may serve as ancillary tests to confirm MCPyV infection in a clinical setting.

Loss of heterozygosity at chromosome 6q23–25 correlates with clinical and histologic parameters in salivary gland adenoid cystic carcinoma

The prognosis of salivary gland adenoid cystic carcinoma (ACC) depends on the clinical stage, the location of the primary tumor, and the histologic growth pattern. ACCs with a cribriform growth pattern have a better prognosis than those with a solid growth pattern; however, clear-cut grading criteria have not yet been established, and therefore prognostic indicators on a molecular level are of special interest. In order to analyze tumor tissue with different growth patterns, cribriform and solid tumor areas of 25 patients were microdissected and separately analyzed for loss of heterozygosity (LOH) at nine polymorphic microsatellite markers located between 6q14 and 6q27. LOH was detected in 19/25 (76%) patients and LOH rates were highest at markers D6S441, D6S310, D6S311 and UTRN, which are located at 6q23–25. Combined analysis of LOH at these four markers shows that in primary tumor subtype foci with cribriform growth pattern LOH is associated with high TNM stages (P<0.01), high T stages (P=0.01), positive lymph node status (P=0.03), an unfavorable disease course (P=0.02), and the presence of >10% solid growth pattern (P=0.05). In contrast, in primary tumor subtype foci with solid growth pattern, no significant differences in LOH rates were found in patients from prognostically and histologically favorable versus unfavorable patient groups. The frequent occurrence of LOH at 6q23–25 and the correlation of LOH rates with prognostic parameters indicate that a prognostically important tumor suppressor gene is located in this chromosomal area.

Expression of the extra domain B of fibronectin, a marker of angiogenesis, in head and neck tumors

Objectives/Hypothesis The extra domain B (ED‐B) of fibronectin, a naturally occurring marker of tissue remodeling and angiogenesis, is expressed in the majority of aggressive solid human tumors, whereas it is not detectable in normal vessels and tissues.

Human herpesvirus type 6 and cytomegalovirus in AIDS-associated Kaposi's sarcoma: No evidence for an etiological association☆

Epidemiological studies indicate that acquired immune deficiency syndrome (AIDS)-associated Kaposis sarcoma (KS) may be caused by an infectious, preferentially sexually transmitted agent. Herpesviruses infections are common sexually transmitted diseases in homosexual men, who are also the main risk group for developing Kaposis sarcoma. To evaluate a possible role of human herpesvirus-6 (HHV-6) and cytomegalovirus (CMV) in the development of AIDS-associated KS, we investigated cutaneous AIDS-associated KS in 26 AIDS patients using the polymerase chain reaction (PCR) and immunohistochemistry (IHC) to detect the presence of HHV-6 and CMV. Human herpesvirus-6 was detected in nine of 26 Kaposis sarcoma specimens (all cases were HHV-6 subtype B) and in eight of 27 normal skin specimens from human immunodeficiency virus (HIV) seropositive and HIV seronegative patients (one case was HHV-6 subtype A and seven cases were HHV-6 subtype B). In two of four patients showing HHV-6 in KS of the skin, the virus also was detected in other investigated tissues, such as heart, lung, liver, kidney, and adrenals. Cytomegalovirus was detected only in AIDS-associated KS (seven of 26 KS specimens) and not in normal skin tissues of HIV-seropositive and HIV-seronegative patients. Cytomegalovirus was detected in other organs of those patients showing CMV in Kaposis sarcoma. Our data indicate that the presence of HHV-6 and CMV in AIDS-associated KS most likely reflects disseminated viral infection. Human herpesvirus-6 and CMV may be cofactors but not the only causative agents for the development of AIDS-associated KS.

Immunohistochemistry in the diagnosis of malignant mesothelioma

The histological diagnosis of malignant mesothelioma of the pleura, especially the distinction from peripheral adenocarcinoma of the lung, may be difficult. The immunohistochemical reports previously published on this subject show diverging results mainly because a variety of antibodies and staining techniques have been used by the different authors. To obtain comparable and reproducible results standard techniques and commercialized antibodies should be applied in routine pathology. In order to investigate the value of immunohistochemistry for the separation of the two entities formalin fixed and paraffin embedded blocks of 47 mesotheliomas and 22 adenocarcinomas were investigated with the PAP technique and commercially available antibodies to carcino-embryonic antigen (CEA), keratin, vimentin, epithelial membrane antigen (EMA), pregnancy specific antigen (SP1), S-100 protein and monoclonal antibody lu-5 (mAB lu-5). CEA positivity was found in all 22 adenocarcinomas examined, but only 2/47 (4%) of all mesotheliomas showed a positive result. SP1 was positive in 13/22 (59%) of the adenocarcinomas, whereas only 3/47 (6%) mesotheliomas were positive for this marker. No significant difference in the rate of positive cases in the adenocarcinoma and mesothelioma group could be found with the other above mentioned antigens. The results of our study indicate that especially CEA, but also SP1 are valuable markers in the diagnosis of malignant mesothelioma.