The "y" symbol: an important classification tool for neoadjuvant cancer treatment.
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Humans↗
Biomedical subjects
Leslie H Sobin
Publications and source records attributed to Leslie H Sobin.
Gastrointestinal stromal tumors: differential diagnosis.
Availability of KIT tyrosine kinase inhibitors for specific treatment of GISTs has magnified the importance of accurate differential diagnosis of GIST from other tumors occurring in the GI tract and abdomen. The general problems in this distinction include histological mimicry of other mesenchymal tumors with GIST, occasional KIT-negativity of GIST, and KIT-positivity of non-GISTs. Up to 5% to 10% gastric GISTs and <2% of intestinal GISTs can be KIT-negative. The identification of these tumors as GISTs is based on knowledge of the spectrum of GIST morphology, and can be supported by molecular diagnosis of KIT and PDGFRA mutations (the latter pertain to gastric tumors). True smooth muscle tumors (rare in GI tract except in esophagus and colon) can be separated from GISTs by the eosinophilic tinctorial quality of tumor cells, positivity for smooth muscle markers, and negativity for KIT. Desmoids can form large GIST-like masses, but are composed of spindled or stellate-shaped cells in a densely collagenous stroma. Negativity for KIT and nuclear positivity for beta-catenin are differentiating features. GI schwannomas, melanoma, and rare primary clear cell sarcoma are S100-positive, usually with characteristic histology. The latter two can be KIT-positive. KIT-positive non-GISTs include some sarcomas, especially angiosarcoma and Ewing sarcoma, extramedullary myeloid tumor, seminoma, and a few carcinomas, notably small cell carcinoma of lung. Spurious KIT-positivity, seen with some polyclonal KIT antibodies, has been a source of confusion leading to probable false-positive results in fibroblastic tumors and occasional other sarcomas, such as leiomyosarcomas. Integration of histological features with carefully standardized immunohistochemistry, supported by KIT and PDGFRA mutation analysis, is the cornerstone of state-of-the art differential diagnosis of GIST. To comprehensively capture all GISTs, KIT immunostains should be performed on all unclassified epithelioid and mesenchymal tumors of the abdomen. This is a US government work. There are no restrictions on its use.
Diagnosis, Differential↗
Occurrence of other malignancies in patients with gastrointestinal stromal tumors.
Almost one-third of gastrointestinal stromal tumors (GISTs) are discovered incidentally during investigative or therapeutic procedures for unrelated diseases. In this regard, GISTs may coexist with different types of cancer, either synchronously or metachronously. The frequency of this association and the spectrum of neoplasms involved have not been sufficiently analyzed. We conducted a review of the literature and our own records for cases with sporadic GISTs and other malignancies, with emphasis on solid tumors. Neurofibromatosis 1 and Carney triad-associated tumors were excluded. Based on these data, there were 518 cancers in 486 GIST patients among 4813 cases with informative data. The overall frequency of second tumors in different series varied from 4.5% to 33% (mean, 13%). A total of 29 patients had multiple malignancies. GISTs of gastric location were most commonly involved with other neoplasms, reflecting their overall high frequency (60%) of all GISTs. The major types of GIST-associated cancers were gastrointestinal carcinomas (n=228; 47%), lymphoma/leukemia, (n=36; 7%), and carcinomas of prostate (n=43; 9%), breast (n=34; 7%), kidney (n=27; 6%), lung (n=26; 5%), female genital tract (n=25; 5%), and carcinoid tumors (n=13; 3%). Other cancers included soft tissue and bone sarcomas (n=15; 3%), malignant melanoma (n=12; 2%), and seminoma (n=6; 1%). Occurrence of collision tumors and metastases of carcinoma or sarcoma into a GIST (the latter noted in 4 cases) can be challenging diagnostic problems. The potential nonrandom association and causal relationship between GIST and other neoplasms remain to be investigated.
Bone Neoplasms↗
Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up.
Gastrointestinal (GI) stromal tumors (GISTs), the specific KIT- or PDFGRA-signaling driven mesenchymal tumors, are the most common mesenchymal tumors of the GI tract. This study analyzed 1091 tumors originally classified as smooth muscle tumors of the small intestine (including jejunum or ileum and excluding duodenum), and found that 906 (83%) of these were GISTs. The GIST patients had 55:45 male-to-female ratio with a median age of 59 years (range, 13-94 years). Only 0.6% of tumors occurred before the age of 21 years and 13.6% before the age of 40 years. The tumors varied from 0.3 to 40 cm (median, 7.0 cm) and most commonly presented with GI bleeding or acute abdomen; 18% were incidentally detected. Histologically, the tumors were relatively monotypic with spindle cell (86%), epithelioid (5%), or mixed patterns (9%). Skeinoid fibers were present in 44% of cases, and their presence was associated with a favorable course. Most epithelioid tumors were malignant, and this morphology sometimes emerged from less cellular and less mitotically active spindle cell tumors, suggesting that it represented a transformation. KIT was immunohistochemically detected in 98%, CD34 in 40%, smooth muscle actin in 34%, desmin in 0.2%, and S-100 protein in 14% of the tumors tested. Outcome was strongly dependent on tumor size and mitotic activity, with an overall 39% tumor-related mortality, twice that for gastric GISTs. Only <3% of tumors <5 cm and < or = 5 mitoses/50 HPF metastasized, whereas 86% of tumors >10 cm and >5 mitoses/50 HPF metastasized. In stark contrast to corresponding gastric tumors, tumors >10 cm with mitotic activity < or = 5/50 HPF and those < or = 5 cm with mitoses >5/50 HPF had a high metastatic rate (>50%); tumors >5 cm < or = 10 cm with low mitotic rate had a 24% metastatic rate. The median survival times of patients with low mitotic rate tumors who died of disease decreased by increasing tumor size. KIT exon 11 mutations were detected in 90 cases, exon 9 mutation in 17 cases, and exon 17 mutation in 1 case; the presence of mutation or mutation type was not prognostically significant. There were no PDGFRA exon 12 or 8 mutations. Systematic data on prognosis of small intestinal GISTs of various size and mitotic activity categories can be helpful in management and surveillance of patients with these tumors.
Adolescent↗
Gastrointestinal stromal tumors in patients with neurofibromatosis 1: a clinicopathologic and molecular genetic study of 45 cases.
Gastrointestinal stromal tumors (GISTs), the specific KIT- or PDFGRA-signaling driven mesenchymal tumors, most commonly occur sporadically, but there seems to be some increased tendency for these tumors to develop in patients with neurofibromatosis 1 (NF1). The clinicopathologic profile, KIT, and PDGFRA mutation status and long-term prognosis of patients with GIST in NF1 are incompletely characterized. In this study, we analyzed 45 patients who had NF1 and GIST. There were 26 females and 19 males with a median age of 49 years (10 years lower than the median age of GIST patients in general). A great majority of tumors occurred in the jejunum or ileum, with multiple tumors occurring in 28 cases. Ten patients had a duodenal and one had a gastric GIST. The most common presentations were gastrointestinal bleeding and anemia, and many patients had intermittent bleeding over several years. The majority of the tumors were small and mitotically inactive; only 7 had mitotic activity >5/50 HPFs and 15 tumors were >5 cm. Associated Cajal cell hyperplasia was common. One patient had an intraabdominal peri-intestinal neurofibroma. Five of 35 patients with follow-up died of metastatic disease; all of these had a tumor >5 cm, mitotic rate >5/50 HPFs, or both; three of these tumors were located in the duodenum. The presence of multiple small tumors was not associated with progressive disease. Most patients with long-term follow-up enjoyed a good prognosis; 2 died of other NF1-associated tumors (malignant peripheral nerve sheath tumors, brain tumor). None of the 16 tumors from 15 patients had a KIT exon 9, 11, 13, or 17 or PDGFRA exon 12 or 18 mutation as is typically seen in sporadic GISTs, indicating that GISTs in NF1 patients have a different pathogenesis than sporadic GISTs.
Adult↗
Brunner's gland hyperplasia and hamartoma: imaging features with clinicopathologic correlation.
OBJECTIVE: The purpose of this essay is to describe, illustrate, and correlate the imaging and pathologic features of Brunner's gland hyperplasia and Brunner's gland hamartoma. CONCLUSION: This article summarizes our experience with pathologically proven cases of Brunner's hyperplasia and hamartoma accessioned into the radiologic pathology archive of the Armed Forces Institute of Pathology.
Adult↗
Duodenal carcinoids: imaging features with clinical-pathologic comparison.
PURPOSE: To retrospectively evaluate the imaging features of duodenal carcinoids with clinical-pathologic comparison. MATERIALS AND METHODS: The institutional review board approved this study; informed consent was not required. The study was HIPAA compliant. The authors retrospectively reviewed the barium studies (n = 20), computed tomographic (CT) scans (n = 16), magnetic resonance (MR) images (n = 2), pathology reports (n = 33), gross pathology photographs (n = 15), and clinical data (n = 33) from 33 patients (16 men and 17 women; age range, 19-90 years; mean age, 52.6 years) with a confirmed diagnosis of duodenal carcinoid admitted into our institution during a 52-year period. The imaging studies were evaluated by consensus of two abdominal radiologists for the number of masses and their location and morphologic characteristics (polypoid or mural). The CT and MR images were also assessed for contrast enhancement characteristics. RESULTS: Most carcinoids were located in the proximal duodenum (10 in the bulb, 19 in the second portion, two in the third portion, and two in the fourth portion). Seventeen patients (52%) had focal intraluminal polypoid masses and 13 (39%) had mural masses; in three patients (9%), the tumor was not visualized at CT. Five of the 33 patients (15%) had multiple carcinoids. CT showed heterogeneous contrast enhancement in all patients who received intravenous contrast material in the arterial or portal venous phases of enhancement. Nonenhancing masses were present in patients who underwent CT during the equilibrium phase. Two patients had Zollinger-Ellison syndrome. Five patients (15%) had neurofibromatosis type 1 (NF-1); four of the five patients (80%) were women, and four patients were African American. In all five patients with NF-1, the carcinoids were located in the periampullary region. CONCLUSION: Duodenal carcinoids are uncommon tumors with a wide clinical-pathologic spectrum. They occur most commonly in the proximal duodenum and manifest as an intraluminal polyp or a mural mass.
Adult↗
Re: Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging.
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Classification↗
On the use and abuse of X in the TNM classification.
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Humans↗
Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up.
Gastrointestinal (GI) stromal tumors (GISTs), the specific KIT- or PDFGRA-signaling driven mesenchymal tumors, are the most common mesenchymal tumors of the GI tract. In this study, we analyzed 1869 cases originally classified as smooth muscle tumors of the stomach and found that 1765 (94%) of these were GISTs. The GISTs had a slight male predominance (55%) with a median age of 63 years. Only 2.7% of tumors occurred before the age of 21 years and 9.1% before the age of 40 years. The tumors varied from 0.5 to 44 cm (median, 6.0 cm) and most commonly presented with GI bleeding; 12% were incidentally detected. Several histologic variants were recognized among the spindle cell tumors (sclerosing, palisaded-vacuolated, hypercellular, and sarcomatous) and of epithelioid tumors (sclerosing, dyscohesive, hypercellular, and sarcomatous). Outcome was strongly dependent on tumor size and mitotic activity. Only 2% to 3% of tumors <10 cm and <5 mitoses/50 HPFs metastasized, whereas 86% of tumors >10 cm and >5 mitoses/50 HPFs metastasized. However, tumors >10 cm with mitotic activity <5/50 HPFs and those <5 cm with mitoses >5/50 HPFs had a relatively low metastatic rate (11% and 15%). A small number of patients survived intra-abdominal metastasis up to over 20 years. Tumor location in fundus or gastroesophageal junction, coagulative necrosis, ulceration, and mucosal invasion were unfavorable factors (P <0.001), whereas tumor location in antrum was favorable (P <0.001). KIT expression was detected in 91% of the cases, CD34 in 82%, smooth muscle actin in 18%, and desmin in 5%; the latter two were favorable (P <0.001). KIT exon 11 mutations were detected in 119 cases; patients with point mutations fared better than those with deletions (P <0.01). PDGFRA exon 18 mutations (total 86 cases) were common in epithelioid GISTs and most commonly represented a D842V point mutation; none of these was prognostically significant. The above results may be helpful for setting the criteria for adjuvant treatment such as Gleevec.
Adolescent↗
Gastrointestinal stromal tumors of the stomach in children and young adults: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases with long-term follow-up and review of the literature.
Gastrointestinal stromal tumors (GISTs), specific KIT- or PDFGRA-signaling driven mesenchymal tumors, are rare in children and young adults, and their clinicopathologic and molecular genetic profile is incompletely understood. In this study, we analyzed 44 gastric GISTs occurring by the age of 21 years. There were 32 females and 12 males, youngest of whom were a 5-year-old boy and an 8-year-old girl. All but 1 of 25 patients under the age of 16 were girls. The patients most commonly received medical attention because of chronic, insidious gastrointestinal bleeding with anemia, less commonly with acute GI bleeding. Only 1 patient had Carney triad with pulmonary chondroma. None of the patients had family members with GIST. The tumors measured from 1.5 to 24 cm (median, 5.6 cm). A total of 21 tumors with specified location were in the antrum and 8 were in the gastric body. Histologically, 26 tumors were composed of epithelioid cells, 12 of spindle cells, and 6 of combination thereof. Mitotic activity varied form 0 to 65/50 HPF (median, 5/50). All but one of the 24 tumors tested were KIT-positive, and 20 were CD34-positive. Eleven patients developed liver or abdominal metastases, and 6 of them died of tumor surviving 5.5 to 35.5 years (median, 16 years) after the first surgery; three of these tumors had a low mitotic activity and size <10 cm. Twenty-one patients were alive with no evidence for disease 7 to 41 years (median, 17 years) after the first surgery. None of the 13 tumors examined (7 of them 8- to 16-year-old females) had KIT exon 9, 11, 13, or 17 or PDGFRA exon 12 or 18 mutation as typically seen in adult GISTs. Gastric GISTs in children have mainly epithelioid morphology, often occur in antrum, and have a somewhat unpredictable but slow course of disease. Their pathogenesis may differ from that of adult GISTs because no KIT or PDGFRA mutations were found; connection with Carney triad seems infrequent despite demographic and histologic similarities.
Adolescent↗
Gastrointestinal schwannomas: CT features with clinicopathologic correlation.
OBJECTIVE: The objective of this study was to describe the CT features of gastrointestinal schwannomas with clinicopathologic correlation. CONCLUSION: Gastrointestinal schwannomas are uncommon mesenchymal neoplasms that are uniquely different tumors from their soft-tissue and central nervous system counterparts. They are homogeneously attenuating, well-defined, mural masses on CT. The lack of low-attenuation hemorrhage, necrosis, and degeneration within the tumor may help distinguish these tumors from gastrointestinal stromal tumors on CT.
Aged↗
Multifocal/multicentric breast carcinoma.
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Breast Neoplasms↗
Clinical and molecular biologic characteristics of early-onset versus late-onset colorectal carcinoma in Filipinos.
A case-control study of Filipino patients who underwent surgical resection for colorectal cancer (CRC) during a 1-year period was undertaken. Thirty-five patients under age 40 years were identified. Paraffin blocks of these and 35 randomly selected patients over age 40 underwent histologic and immunohistochemical evaluation. Markers chosen for evaluation included the apoptosis-associated gene products (p53 and bcl-2), a tumor proliferation activity-related factor (Ki-67), and the markers (MLH1 and MSH2) of DNA microsatellite instability (MSI). Results were correlated with age and the stage and location of the tumor. The average age of the early-onset group was 30.7 years compared to the late-onset group at 67.0 years; and the male/female ratio was equivalent. The younger patients had a significantly higher Dukes' stage, the tumors were more poorly differentiated, and they were more frequently of the mucinous and signet ring cell histopathologic type. Expression of p53 was higher in the younger patients ( p < 0.001) and was independent of the degree of differentiation or the stage of the tumor. No differences of expression were noted for the other markers measured. The increased frequency of CRC in Filipino patients less than 40 years of age offers a unique opportunity to gain a better understanding of carcinogenesis, which might be exploited during diagnosis and management. The differences noted between the early- and late-onset CRC are provocative and provide an impetus for increased screening in Filipinos.
Adenocarcinoma↗
The process for continuous improvement of the TNM classification.
The TNM classification is a worldwide benchmark for reporting the extent of malignant disease and is a major prognostic factor in predicting the outcome of patients with cancer. The objectives for cancer staging were defined by the International Union Against Cancer (UICC) TNM Committee almost 50 years ago and are still broadly applicable today. To keep pace with the modern demands of evidence-based practice, the UICC introduced a structured process for introducing changes to the TNM classification. The elements of the TNM process were determined to include the development of unambiguous criteria for the information and documentation required to consider changes in the classification, establishment of a well-defined process for the annual review of relevant literature, formation of site-specific expert panels, and the participation of experts from all over the world in the TNM review process. Communication between the oncology community and those involved in the TNM classification was established as being essential to the success of the process. The process, which was introduced in 2002, will be tested over the next 3-4 years and evaluated. In addition to the formal process, individual initiative, involvement by the national staging committees, and group consensus are required. Furthermore, increased involvement by the experts should improve the understanding and dissemination of the TNM classification.
Communication↗
A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential.
Gastrointestinal stromal tumors (GISTs) are KIT expressing spindle cell, epithelioid and rarely pleomorphic mesenchymal tumors. The majority of GISTs show gain-of-function KIT mutations. However, GISTs without KIT mutations and GISTs with weak or lack of immunohistochemical KIT expression have also been reported. Recently, gain-of-function mutations in exon 18 (activation loop) and exon 12 (juxtamembrane domain) of the PDGFRA were identified in such tumors. The purpose of this study was to test the hypothesis that PDGFRA mutation may define a specific clinicopathologic subgroup of GISTs. A total of 447 KIT exon 11 (juxtamembrane domain) mutation-negative GISTs were studied. DNA samples were obtained from formaldehyde-fixed paraffin-embedded tissues. Genomic sequences of PDGFRA exons 18 and 12 were evaluated for the mutations by PCR amplification and direct sequencing. PDGFRA exon 18 mutations were identified in 122 of 346 (35.3%) gastric GISTs and two of 75 (2.7%) intestinal GISTs. A great majority of these mutations represented simple T to A missense mutation at the codon 842 leading to substitution of the valine for aspartic acid (D842 V). However, in-frame deletions and deletions with point mutations clustering between codons 841-847 were found in approximately 23% of all exon 18 mutations. Mutations in PDGFRA exon 12 were found only in 10 of 170 (5.8%) gastric and one of 54 (1.9%) intestinal GISTs negative for KIT exon 11 and PDGFRA exon 18 mutations. There were seven substitutions of aspartic acid for valine at codon 561 (V561D) and four in-frame deletions with point mutations clustering between codons 566 and 571. The majority of GISTs with PDGFRA mutations had pure or predominant epithelioid morphology. Low mitotic activity, < or =5 mitoses/50HPF was detected in 81% of analyzed GISTs including larger, >5 cm tumors. Based on long-term follow-up (average 135 months), a majority (83.5%) of GISTs with PDGFRA mutations followed a benign course.
Adult↗
Neuroendocrine tumors of the appendix.
The vast majority of neuroendocrine neoplasms of the appendix are carcinoid tumors. Most are of enterochromaffin (EC) cell type, although rare examples are of L cell type. EC cell carcinoids of the appendix differ from those encountered elsewhere in the gastrointestinal system. For example, they are remarkably common given the small size of the appendix, are usually benign, occur in younger patients, and typically contain sustentacular cells that express S-100. Origin from subepithelial neuroendocrine cells could explain these characteristics. It has also been suggested that most appendiceal carcinoids are hyperplastic rather than neoplastic, although this hypothesis requires further study. Nevertheless, truly neoplastic EC cell carcinoids of the appendix undoubtedly occur, and those greater than 2 cm in diameter have a significant risk of producing distant metastases. Carcinoid syndrome is a very rare presentation. Tubular carcinoids are unusual benign neoplasms; it has been proposed that they represent L cell carcinoids with a predominant tubular pattern of growth. Goblet cell carcinoids tend not to produce a grossly visible tumor mass but diffusely infiltrate the wall. They typically exhibit tight clusters of goblet cells, usually with scattered neuroendocrine cells and sometimes with Paneth cells, sometimes surrounding a small lumen. They may behave as a low-grade malignancy. The distinction between goblet cell carcinoid and other types of tumor is of great importance because of the implications for treatment and prognosis. Frank adenocarcinoma can arise from goblet cell carcinoids, and tumors with both components are classified as mixed goblet cell carcinoid-adenocarcinoma. The carcinoma component of the latter determines their prognosis, which would be worse than for a goblet cell carcinoid alone.
Appendiceal Neoplasms↗