Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “MALT”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources
PubMed2003

Helicobacter pylori genotyping in gastric adenocarcinoma and MALT lymphoma by multiplex PCR analyses of paraffin wax embedded tissues.

BACKGROUND: Gastric infection with Helicobacter pylori is the major cause of chronic active gastritis and is associated with the pathogenesis of peptic ulcer and gastric carcinoma. Gastric mucosal damage involves both host and H pylori dependent factors, such as the presence of the cag pathogenicity island and allelic variations of the vacA and iceA genes. AIMS: To evaluate the association of these virulence factors with the development of gastric malignancies, a retrospective study was performed on archived tissue routinely obtained for diagnostic histopathology. METHODS: DNA was extracted from formalin fixed, paraffin wax embedded gastric tissue sections of 93 patients with chronic active gastritis (n = 39), adenocarcinoma (n = 28), or mucosa associated lymphoid tissue (MALT) lymphoma (n = 24). The extracted DNA was used to perform a polymerase chain reaction based, simultaneous analysis of the following: (1) cagA status, (2) allelic variation of the iceA genes (iceA1, iceA2), allelic variation of the signal peptide (s1a, s1b, s2) and the midregion (m1, m1a, m2) of the vacA gene. RESULTS: The iceA1 gene showed a 3.6 fold and the vacA s1a variant a 4.2 fold higher prevalence in gastric adenocarcinoma than in gastritis. The combined presence of both the vacA s1a and iceA1 genes had a 5.6 fold higher frequency in adenocarcinoma. The vacA m2 allele was the predominant subtype in MALT lymphoma and the combination of the vacA m2 subtypes with the vacA s1 and the iceA1 variants occurred in MALT lymphoma nearly five times more often than in chronic active gastritis. CONCLUSIONS: Certain H pylori subtype combinations possess a differentiating and predictive value for the development of gastric adenocarcinoma and MALT lymphoma.

Adenocarcinoma↗
PubMed2005

[Utility of MALT (Münchner Alkoholismus Test) questionnaire for detection of alcoholism in women].

BACKGROUND AND OBJECTIVE: Patients identified as risk drinkers usually fill a questionnaire in order to assess their alcohol dependence. In our setting, the Münchner Alkoholismus Test (MALT) has been recommended, but there are not enough data about its validity and accuracy, particularly in women. The aim of this study was to assess the psychometric properties of this test in a female population. SUBJECTS AND METHOD: 414 woman were recruited in a Health Center and a Specialized Center for addiction treatment. MALT test and the Schedule for Clinical Assessment in Neuropsychiatry (SCAN) semistructured interview (gold standard; DSM-IV and CIE-10 criteria) were performed to all patients. Internal consistence, criteria validity and the most diagnostic efficacy cut-off point (ROC curves) were assessed. RESULTS: The MALT average (standard deviation) score of the whole sample was 3.98 (9.48) points (95% confidence interval [CI], 3.07-4.90). Cronbach alpha was 0.939 (95% CI, 0.931-0.947). With a score of 4 or more points, the test had 100% (95% CI, 98.9-100) sensitivity and 95.4% (95% CI, 95.2-95.5) specificity. CONCLUSIONS: The MALT test has an excellent internal reliability and extremely good diagnostic accuracy. It is very useful to detect alcohol dependence in women. A cut-off of 4 or more points is proposed.

Adolescent↗
PubMed2005

High relapse rate in patients with MALT lymphoma warrants lifelong follow-up.

BACKGROUND: B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT lymphoma) is thought to be an indolent disease, with a good prognosis following various forms of treatment. Little, however, is known about the rate and pattern of relapse following successful treatment. PATIENTS AND METHODS: We have analyzed time to and pattern of relapse in patients with MALT lymphoma, along with investigation of t(11;18)(q21;q21), t(1;14)(p22;q32), and t(14;18)(q32;q21) involving IGH/MALT1, trisomy 3, and trisomy 18. Eighty-six patients achieving complete remission (CR) after initial therapy with sufficient follow-up data were available. Primary site of disease was the stomach (n = 36), salivary gland (n = 19), ocular adnexa/orbit (n = 12), lung (n = 8), thyroid (n = 5), breast (n = 3), liver (n = 2), and skin (n = 1). RESULTS: Thirty-two patients (37%) relapsed between 14 and 307 months (median 47 months) after initial CR. Ten relapses were local, whereas the remaining patients relapsed in a distant organ. Eight of 36 gastric versus 24 of 50 nongastric MALT lymphomas (P = 0.02) relapsed. Five patients had a second recurrence 26 to 56 months after a second CR. Relapse rates were not related to forms of initial treatment. Chromosomal aberrations were detected in 14 of 28 (50%) relapsing patients, and chromosomal alterations were identical at diagnosis and relapse. No significant association of any of the genetic changes investigated with relapse was found. Interestingly, patients with t(11;18)(q21;q21) had a significantly longer median time to relapse (76 months) than patients without this translocation (29 months; P = 0.012). CONCLUSIONS: In view of the late relapses seen in our series, lifelong observation of all patients treated for MALT lymphoma seems to be required.

Adult↗
PubMed2003

Female patient with a history of Hashimoto's thyroiditis, diagnosed with MALT lymphoma of both breasts.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphomas are a distinct subgroup of non-Hodgkin's lymphomas with preferable localization in the gastrointestinal tract. PATIENTS AND METHODS We describe the unusual case of a 48-year-old female patient, who was diagnosed with simultaneous MALT lymphoma of both breasts. Cervical, axillary and retroperitoneal lymph nodes were slightly enlarged, indicating an infiltration by the lymphoma. In her medical history the patient suffered from Hashimoto's thyroiditis. After 6 cycles of chemotherapy with CHOP regimen, the patient achieved complete remission. CONCLUSION: To our knowledge, this is the first case describing a patient with MALT lymphoma of the breast and a history of Hashimoto's thyroiditis. As patients suffering from autoimmune disorders, especially Sjögren's syndrome and Hashimoto's thyroiditis, are at a higher risk to develop B-cell lymphoma, we assume that Hashimoto's thyroiditis favored development of MALT lymphoma in our patient.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2007

Activity of rituximab plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone in patients with relapsed MALT lymphoma.

BACKGROUND: Various chemotherapeutic agents as well as the anti-CD20 antibody rituximab (R) have been tested in patients with mucosa-associated lymphoid tissue (MALT) lymphoma, but no standard chemotherapeutic regimen has emerged so far. Judging from the data obtained in various types of lymphoma, the activity of R appears to be enhanced by combination with chemotherapy. As no data on this topic exist for MALT lymphoma, we have retrospectively analysed our experience with R plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone (R-CHOP/R-CNOP) in patients with relapsed MALT lymphoma. PATIENTS AND METHODS: A total of 26 patients were identified, 15 were administered R-CHOP while 11 patients were given R-CNOP due to age >65 years or pre-existing cardiac conditions. Cycles were repeated every 21 days, and restaging was performed after 4 cycles of therapy. In case of complete remission, 2 further cycles were administered for consolidation while patients achieving partial remission or stable disease after restaging were given 4 further courses. RESULTS: A total of 170 cycles were administered to our patients (median 6, range 2-8). Twenty of the 26 patients (77%) achieved a complete remission and 6 (23%) a partial remission. Toxicities were mainly haematological, with WHO grade III/IV leukocytopenia occurring in 5 patients. After a median follow-up of 19 months (range 10-45), all patients are alive: 22 are in ongoing remission, while 4 have relapsed between 12 and 19 months after treatment. CONCLUSIONS: Our data demonstrate a high activity of R-CHOP/R-CNOP in relapsing MALT lymphoma irrespective of prior therapy.

Adult↗
PubMed2002

High incidence of t(11;18)(q21;q21) in Helicobacter pylori-negative gastric MALT lymphoma.

In approximately 5% to 10% of gastric mucosa-associated lymphoid tissue (MALT) lymphomas, evidence of Helicobacter pylori infection is absent, and their pathogenesis is poorly understood. We reviewed the clinical data and histology, and we examined t(11;18)(q21;q21) and BCL10 expression pattern in 17 such cases. In each case, the absence of H pylori was confirmed by negative serology and histology/immunohistochemistry. Five cases with stage I(E) disease were first treated with antibiotics, and none of them showed any endoscopic or histologic response. Review of the histology failed to identify any apparent difference between gastric MALT lymphomas with and without H pylori infection. Reverse transcription-polymerase chain reaction (RT-PCR) showed t(11;18)(q21;q21) in 9 (53%) of 17 cases, more frequent in lymphomas at stage II(E) or above (5 of 6) than those at stage I(E) (3 of 10). Two t(11;18)(q21;q21)-positive lymphomas were treated by partial gastrectomy and more than 16 years later showed lymphoma relapse in the gastric stump with dissemination to other mucosal sites, poorly responsive to therapy. BCL10 nuclear expression was observed in 7 of 8 t(11;18)(q21;q21)-positive cases and 4 of 7 t(11;18)(q21;q21)-negative cases, including one case suspicious for a BCL10-involved chromosomal translocation. Our results show that t(11;18)(q21;q21) occurs at a high frequency in H pylori-negative gastric MALT lymphomas. Translocation-positive gastric MALT lymphomas tend to be aggressive, and patients with such lymphomas might benefit from prompt treatment and close follow-up.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Detection of the t(11;18) API2/MALT1 translocation associated with gastric MALT lymphoma in routine formalin-fixed, paraffin-embedded small endoscopic biopsy specimens by robust real-time RT-PCR.

The t(11;18)(q21;q21) API2/MALT1 translocation is a specific chromosomal abnormality in extranodal marginal B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) type, particularly in those occurring in the stomach and lungs. Identification of t(11;18) may aid in the diagnosis of MALT lymphoma and strongly predicts resistance of gastric MALT lymphoma to Helicobacter pylori eradication therapy. We developed a robust real-time reverse transcription-polymerase chain reaction (RT-PCR) procedure to efficiently detect t(11;18) in virtually all types of specimens used in routine diagnostic workups. We blindly tested 40 samples from 38 patients with gastric MALT lymphoma; 10 (25%) of 40 samples, or 8 (21%) of 38 patients were positive for t(11;18). In contrast, t(11;18) was not detected in 8 cases of gastric large B-cell lymphoma, 11 cases of chronic active gastritis, and 16 samples unrelated to lymphoma. Our findings suggest that real-time RT-PCR for t(11;18) may be a valuable tool with much relevance in the current clinical management scheme.

Biopsy↗
PubMed2002

A solitary minute thyroid lymphoma of MALT-type without lymphoid thyroiditis.

Most of the primary thyroid malignant lymphomas have been considered of mucosa-associated lymphoid tissue (MALT) type and arise from lymphocytic thyroiditis. We report an uncommon case of a 67-yr-old man who underwent total thyroidectomy for multinodular goiter with tracheal compression. At histopathologic examination, we discovered a minute (3-mm diameter) lesion of low-grade thyroid lymphoma of MALT type without any lymphocytic thyroiditis lesion on 33 section levels of the entire thyroid gland. No general inflammatory, autoimmune, or lymphomatous disorder has been evidenced both at staging and after 30 mo of follow-up. MALT-type low-grade lymphoma may, in some instances, develop de novo within the thyroid without an antecedent MALT-type lymphoma.

Aged↗
PubMed2006

Nongastric marginal-zone B-cell MALT lymphoma: prognostic value of disease dissemination.

The aim of this study is to describe the clinical features and define the prognostic significance of disease dissemination in a large series of nongastric marginal-zone B-cell mucosa-associated lymphoid tissue (MALT) lymphomas. We studied 208 patients with nongastric marginal-zone B-cell MALT lymphoma diagnosed and treated from 1991 to 2004. Ninety percent of the patients had a single site of MALT involvement--skin (26%), salivary glands (18%), orbit (14%), Waldeyer's ring (13%)--and 39% and 28% had nodal involvement and bone marrow involvement, respectively. After a median follow-up of 2.7 years, the median event-free survival (EFS) time was 2.4 years, and the median overall survival (OS) time was not reached. On univariate analysis, the features significantly associated with longer EFS and OS times were the following: single MALT site involvement (OS), localized disease (EFS and OS), no nodal disease (EFS and OS), skin and orbit lymphoma (OS), and stage IV disease without bone marrow involvement (OS). On multivariate analysis, both bone marrow and nodal involvement were associated with shorter OS. This study describes the clinical features and the natural history of nongastric marginal-zone lymphomas and highlights that the dissemination to lymph nodes and bone marrow is associated with a poorer outcome.

Adult↗
PubMed2006

Primary breast mucosa-associated lymphoid tissue (MALT) lymphoma with high-grade transformation evidenced by prominent lymphoepithelial lesions.

Primary breast lymphoma, particularly primary mucosa-associated lymphoid tissue (MALT) lymphoma, is a rare disease. We report here a case of a MALT lymphoma of the breast with high-grade transformation. An 84-year-old woman presented with a Pagetoid mass in her right breast. After a clinical diagnosis of breast cancer, T2N1M0, stage II B, she underwent mastectomy with axillary lymph node dissection. She had no history of autoimmune disease such as Hashimoto thyroiditis or Sjögren disease. Pathologically the tumor tissue was composed of small to large lymphoid cells. The large cells contained a considerable number of centroblasts, forming a sheet-like proliferation centrally. Among the small cells many small cleaved cells were present, which were more predominant in the peripheral areas. Immunohistochemistry revealed that these cells were positive for CD20 and CD79a. The tumor cells infiltrated the ductular epithelial cells, distorting the duct structures, to form lymphoepithelial lesions. Immunohistochemistry for cytokeratin and CD20 was helpful for identification. No germinal centers were formed. MALT lymphoma with high-grade transformation was diagnosed. Rituximab (anti-CD20 antibody) was prescribed as systemic treatment without chemotherapy or irradiation. After 18 months, no tumor recurrence was observed. We emphasize the importance of lymphoepithelial lesions for the diagnosis of MALT lymphoma of the breast.

Aged↗
PubMed2002

Pulmonary low-grade MALT-lymphoma associated with localized pulmonary amyloidosis. A case report.

We report on a female patient, who, at the age of 63 years, was found to suffer from low-grade MALT-lymphoma localized at her right upper eyelid. At the time of initial diagnosis, clinical staging showed no further organ involvement. Within the following two months, nodular infiltrates occurred in both lungs. Histopathological investigation of the pulmonary lesions showed pulmonary involvement by the low-grade MALT-lymphoma associated with large globular amyloid deposits of lambda-light chain origin. Since the tumor cells of the MALT-lymphoma showed restriction to lambda-light chain the amyloid deposits in this case were interpreted as being related to the MALT-lymphoma.

Amyloidosis↗
PubMed2005

Trisomy 3 may predict a poor response of gastric MALT lymphoma to Helicobacter pylori eradication therapy.

AIM: To investigate the relation of the response to Helicobacter pylori eradication therapy to the depth of tumor invasion and chromosome abnormalities in patients with mucosa-associated lymphoid tissue (MALT) lymphoma and to determine the clinical value of aneuploidy. METHODS: We studied 13 patients with localized gastric MALT lymphoma of stage E1. Before eradication therapy, the depth of tumor invasion was assessed by endoscopic ultrasonography in 8 patients and by endoscopic examination and gastrointestinal series in the remaining patients. To detect chromosomal abnormalities, paraffin-embedded tissue sections of diagnostic biopsy specimens underwent tissue-fluorescence in situ hybridization (FISH), using chromosome-specific alpha-satellite DNA probes for chromosomes 3,7,12, and 18 and YAC clones for t(11;18)(q21;q21). RESULTS: Seven of the 13 patients had complete regression (CR) in response to H pylori eradication therapy. No patient with CR had submucosal tumor invasion. Trisomy 18 was seen in 1 patient with CR, and both trisomies 12 and 18 were present in another patient with CR. All patients with no response or progressive disease had deep submucosal tumor invasion and showed t(11;18)(q21;q21) or trisomy 3. Trisomy 7 was not detected in this series of patients. CONCLUSION: The depth of tumor invasion is an accurate predictor of the response of stage E1 MALT lymphoma to H pylori eradication therapy and is closely associated with the presence of chromosomal abnormalities. Trisomy 3 may predict the aggressive development of MALT lymphoma.

Aged↗
PubMedDate not supplied

Endoscopic patterns of primary gastric MALT lymphoma.

Primary low grade B-cell lymphoma of the mucosa associated lymphoid tissue (MALT), is an uncommon malignancy with a prolonged period of localized disease, and a possible transition to a high grade MALT lymphoma. The endoscopic diagnosis is often difficult, because of the various macroscopy patterns. The endoscopic aspects seen in 14 patients diagnosed and treated for primary gastric MALT lymphomas, were reviewed. Four main patterns were recognized: 1/Large ulcerations (n = 6, 42.9%), 2/Polypoid lesion (n = 2, 14.3%), 3/Gastritis with small ulcerations (n = 4, 28.5%), and 4/Atypical mucosal relief (AMR): erythema, nodularity, edematous or infiltrated folds (n = 2, 14.3%). In 10 cases (71%) AMR was associated with another endoscopic pattern. Histologically the tumors were of low grade (n = 11) and high grade (n = 3). On initial endoscopy a diagnosis of malignancy was done in 6 out of the 7 patients (85.7%) with large ulcers and the large polypoid mass; in contrast, an adequate endoscopic diagnosis was made in only 3 out of the 7 patients (42.8%) with ulcerative gastritis, AMR, and the small polypoid lesion. The endoscopic aspect of the latter group, representing 50% of all patients and 63.6% of the group with low grade MALT lymphomas, was indistinguishable from a benign lesion. Therefore it is important to be aware of this entity and perform biopsies in every patients with abnormal endoscopic findings.

Aged↗
PubMed1999

[Non-gastric mucosa-associated lymphoid tissue (MALT) lymphomas: analysis of 14 patients].

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphomas are a well defined group of B-cell non-Hodgkin's lymphomas, that arise in a wide variety of extranodal sites, most frequently in the stomach and related to Helicobacter pylori infection. The aim of the present study was to analyze the presenting features, natural history and outcome in 14 patients with non-gastric MALT lymphoma. PATIENTS AND METHODS: The main clinical data, treatment and outcome were recorded for the 14 patients with non-gastric MALT lymphoma diagnosed at a single institution in a 12 year period. The median age was 68 years and 13 patients were females. Diagnosis was made according to the REAL classification criteria. RESULTS: The initial location was thyroid (3 patients), parotid (three), submaxilar gland (three), skin (two), Waldeyer's ring (one), breast (one), lung (one), small bowel (one), liver (one) and ovary (one). At diagnosis 3 patients had > or = 2 extranodal involved sites. Autoimmune disorders were present in 5 patients: Hashimoto's thyroiditis (three), Sjögren's syndrome (one) and both (one). Two patients had a poor performance status (ECOG > 1) and B-symptoms. Five patients (36%) were in stage IV, two of them because of bone marrow infiltration. All patients had a normal serum LDH level, and 5 had high beta 2-microglobulin level. The treatment consisted in surgical resection (2 patients), surgery and radiotherapy (one), surgery and chemotherapy (two), chemotherapy and radiotherapy (two) and chemotherapy alone (7 patients, three of them with doxorubicin-containing regimens). Twelve patients were evaluable for response. Complete response, partial response and failure rates were 75, 17 and 8%, respectively. Two of the 11 responders progressed, one of them with advanced stage disease. The actuarial 4-year disease-free survival was 77% (CI 95%: 47-100%). After a median follow-up of 3.4 years, 100% of the patients were alive. CONCLUSION: Non-gastric MALT lymphomas may be associated with autoimmune disorders, may present as disseminated disease and have a very good outcome.

Adult↗
PubMedDate not supplied

Low-grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the gallbladder.

Mucosa-associated lymphoid tissue (MALT) lymphomas arise in most cases in the gastrointestinal tract, and are usually of low-grade B cell origin. MALT lymphomas may rarely occur in organs where lymphoid tissue is sparse, especially following inflammatory conditions. Primary lymphomas of the gallbladder are extremely rare, and MALT lymphoma has been reported only twice. We herein describe the third case of low-grade MALT lymphoma of the gallbladder, which exhibits an unusual clinical behavior. The exceptionally advanced stage of the disease stresses the importance of early operation when cholecystectomy is indicated.

Aged↗
PubMed1999

Serum soluble Fas antigen in gastric MALT (mucosa-associated lymphoid tissue) lymphoma patients.

We measured the serum level of soluble Fas (sFas) antigen in gastric MALT (mucosa-associated lymphoid tissue) lymphoma patients to investigate immune response of B lymphoma cells in gastric MALT lymphoma. The serum sFas antigen levels in 21 patients with Helicobacter pylori (HP)-positive MALT lymphoma were 4.51+/-0.25 (mean+/-SD) in the high grade malignant group (n=9) that demonstrated diffuse large cell (DL) components and 2.53+/-0.46 (mean+/-SD) in the low grade malignant group (n=12) that did not demonstrate DL components. Among 12 patients who underwent HP eradication therapy, the blood sFas antigen level lowered after eradication in 7 out of 10 patients who showed complete response or partial response, while sFas antigen level did not decrease in the 2 patients who showed no change or progression of the disease. In the high grade malignant group, 2 of 3 patients who underwent HP eradication treatment showed a mild decrease in the sFas antigen level as well as an improvement on endoscopic and histological examinations, but these sFas level were not normalized. The blood sFas antigen level tended to coincide with pathological activity and malignancy, suggesting that the sFas antigen level may be a prognostic indicator and useful index for the response of HP eradication treatment in gastric MALT lymphoma.

Apoptosis↗
PubMed2000

Detection of aberrant isotype switch recombination in low-grade and high-grade gastric MALT lymphomas.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma originates from reactive lymphocytic infiltrates during chronic gastritis, closely associated with Helicobacter pylori infection. MALT lymphomas may be either "low grade" or "high grade," and transformation from low grade to high grade can occur. To obtain information on the maturational state of MALT lymphoma cells, we investigated their ability to undergo isotype switch recombination, which together with immunoglobulin variable gene somatic mutation, contributes to normal B-cell maturation. Using specific probes for the immunoglobulin heavy-chain (IgH) switch regions, we found by Southern blot that 3 out of 5 low-grade cases and 2 out of 2 high-grade cases showed rearrangements within IgH switch regions, which appeared aberrant in 4 of the 5 cases. The cloning of two rearranged fragments from one low-grade and one high-grade case confirmed the aberrant nature of the rearranged fragments. A deletion from the switch mu region (S mu) to the first constant mu exon (C mu 1) and a second deletion from the second constant mu exon (C mu 2) to the gamma 3 region (gamma 3) was detected in the low-grade case. In the high-grade case, there was a deletion of the IgH intronic enhancer (E mu) and a 336-base pair (bp) insertion into the S mu region of a gene (KIAA0307) normally located at 15q24. These data demonstrate for the first time the ability of MALT lymphoma cells to undergo aberrant isotype switch recombinations, which might be directly involved in the development or progression of malignancy.

B-Lymphocytes↗
PubMed2000

[MALT lymphoma of the larynx].

We describe a 25-year-old Japanese woman with a MALT-type lymphoma of the larynx. She presented with a one-year history of hoarseness and increasing pain in the larynx. A small tumor was found on the left side of the false cord, and was biopsied under laryngoscopy in the department of laryngology. Histological examination showed the presence of centrocyte-like cells infiltrating the submucosa and forming lymphoepithelial lesions. The neoplastic cells were CD20+, CD79a+, and CD5-. Staining for keratin with CAM 5.2 highlighted the infiltrated epithelium. Analysis of DNA extracted from the biopsy specimen showed a clonal immunoglobulin heavy chain gene rearrangement, confirming the histological diagnosis of extranodal marginal zone B-cell lymphoma of the MALT type. To our knowledge, only 6 cases of MALT lymphoma of the larynx have been reported previously. The presence of MALT lymphomas arising at rare sites emphasizes the importance of accurate diagnosis and appropriate clinical management. Patients require careful periodic evaluation in order to time the therapy appropriately, and to avoid overtreatment and complications of therapy, including secondary malignancies.

Adult↗