ABSTRACT
Although twin studies indicate that inherited genetic factors contribute to about 35% of colorectal cancers (CRC), the exact genetic background has currently been elucidated in only 5-10% of cases. These comprise several hereditary cancer predisposition syndromes that present with a high number of syn- or metachronous neoplasms within an affected person and/or family. Many of these tumors exhibit typical histopathological changes. In general, one should discriminate between cancer syndromes associated with adenomatous and non-adenomatous (i.e., hamartomatous) polyps, the latter being quite rare. The patient's age often serves as a substantial hint to hereditary cancer. The next step of diagnostic work-up includes analysis of microsatellite instability (MSI) together with immunohistochemical detection of a loss of expression in one of the most frequently affected mismatch repair genes (MSH2, MSH6; MLH1, PMS2). Finally, the molecular demonstration of a gene mutation in the blood or germline is the most expensive and tedious procedure. This requires a signed informed consent from the patient after appropriate genetic counseling.
Subject(s)
Colonic Neoplasms/genetics , Colonic Neoplasms/pathology , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Rectal Neoplasms/genetics , Rectal Neoplasms/pathology , Colonic Neoplasms/diagnosis , Colorectal Neoplasms/diagnosis , Diagnosis, Differential , Genetic Predisposition to Disease , Humans , Microsatellite Repeats/genetics , Rectal Neoplasms/diagnosisABSTRACT
BACKGROUND: Synovial sarcoma is a rare soft tissue malignancy that most often occurs in the extremities of young adults. Approximately 3 % of these mesenchymal malignant tumors occur in the head and neck region. Up to now about 100 cases have been published. PATIENTS: We report on two cases of a synovial sarcoma of the hypopharynx. In the first case the patient died 3.5 years after beginning of therapy including all therapeutical efforts (surgery, chemotherapy, radiotherapy). The second patient with a synovial sarcoma of his left hypopharynx and a distant metastasis in his 8th thoracic vertebral body is actually treated by neoadjuvant chemotherapy and included into a clinical study to optimize therapy of advanced soft tissue sarcomas. Further surgical treatment depends on the success of this therapeutic approach. CONCLUSION: Despite multitherapeutic approaches over all 5-year survival rates for advanced synovial sarcomas of the head and neck have moderately improved in the recent decades and an ideal treatment has not yet surfaced. Modification of accepted treatment modalities is discussed and therapy options in controlled clinical studies are described.
Subject(s)
Hypopharyngeal Neoplasms , Sarcoma, Synovial , Adult , Chemotherapy, Adjuvant , Clinical Trials as Topic , Combined Modality Therapy , Humans , Hypopharyngeal Neoplasms/diagnosis , Hypopharyngeal Neoplasms/drug therapy , Hypopharyngeal Neoplasms/mortality , Hypopharyngeal Neoplasms/pathology , Hypopharyngeal Neoplasms/radiotherapy , Hypopharyngeal Neoplasms/surgery , Hypopharynx/pathology , Immunohistochemistry , Magnetic Resonance Imaging , Male , Neoadjuvant Therapy , Radiotherapy Dosage , Sarcoma, Synovial/diagnosis , Sarcoma, Synovial/drug therapy , Sarcoma, Synovial/mortality , Sarcoma, Synovial/pathology , Sarcoma, Synovial/radiotherapy , Sarcoma, Synovial/surgery , Time FactorsABSTRACT
Few and conflicting cytogenetic data are available concerning the chromosomal constitution of (mainly gastric) extranodal marginal zone B-cell non-Hodgkin's lymphoma arising from mucosa-associated lymphoid tissue (MALT)-type lymphoma. The majority of salivary gland MALT lymphomas are thought to develop from longstanding Sjögren's syndrome/benign lymphoepithelial lesion (BLEL). We tried to achieve a better comprehension of related cytogenetic alterations by comparing DNA-ploidy and numerical chromosomal (#) aberrations, assessed by different techniques of DNA cytometry (image cytometry) and interphase cytogenetics using nonradiographic in situ hybridization (centromere specific probes for #3, 7, 12, 18) on 12 cases of BLEL, 13 low-grade MALT lymphomas (LG-MALT-L) and 4 high-grade MALT lymphomas (HG-MALT-L) of salivary gland. Both techniques were applied on tissue sections preferentially, enabling a reliable measurement of histomorphologically identified areas. No case of BLEL showed cytogenetic abnormalities. Three of 4 HG- and 2 of 13 LG-MALT-L exhibited complex chromosomal gains in nonisotopic in situ hybridization, which were reflected by DNA nondiploidy in image cytometry. In 6 of 13 LG- and lof 4 HG-MALT-L, one or two numerical chromosomal aberrations were demonstrated by nonisotopic in situ hybridization, which could not be resolved by image cytometry. In the 11 DNA-diploid LG-MALT-L, trisomies 18, 3, and 12 were found in 36, 12, and 9%, respectively. In conclusion, comparing BLEL, which showed no chromosomal aberrations, with LG- and HG-MALT-L, an increase in frequency and number of numerical aberrations and DNA nondiploidy was seen. Peritetraploid DNA nondiploidy might be characteristic for HG-MALT-L of salivary gland as it is a rare finding in MALT lymphomas of other sites. It is unclear whether the documented chromosomal aberrations in LG-MALT-L, especially increased rate of trisomy 18, indicate a pathogenic impact or merely reflect genetic instability.
Subject(s)
DNA, Neoplasm/analysis , Lymphoma, B-Cell, Marginal Zone/genetics , Salivary Gland Neoplasms/genetics , Sjogren's Syndrome/genetics , Adult , Aged , Aged, 80 and over , Cell Nucleus/genetics , Cell Nucleus/pathology , Cell Separation , Chromosome Aberrations , Female , Flow Cytometry , Humans , Image Cytometry , In Situ Hybridization , Interphase , Lymphoma, B-Cell, Marginal Zone/pathology , Male , Middle Aged , Ploidies , Salivary Gland Neoplasms/pathology , Sjogren's Syndrome/pathologyABSTRACT
Several salivary gland diseases present with the histomorphological features of a lymphoepithelial lesion with or without cyst formation. Some of the most important differential diagnoses (Sjögren's syndrome, marginal zone B-cell lymphoma, HIV-associated cystic lymphoepithelial lesion) are systemic diseases and require further investigation and therapy. However, in small biopsy specimens and in cases without relevant clinical information an exact diagnosis may be difficult to obtain. We have recently determined that the characteristic lymphoepithelial duct lesions develop by proliferation of basal cells of striated ducts, while we could not confirm the previously postulated participation of myoepithelial cells ("epimyoepithelial lesion/sialadenitis"). Although these duct lesions are typical of Sjögren's syndrome, they manifest in several diseases of salivary glands, exhibiting characteristic patterns concerning frequency and localization. This review discusses the most important lymphoepithelial diseases of salivary glands with respect to clinical presentation and histomorphology. Particular emphasis is placed on the lymphoepithelial duct lesions.
