Pathology and genetics of tumors of soft tissue and bone

Diagnosis of gastrointestinal stromal tumors: A consensus approach.

ObjectiveTo analyze the outcome of 200 patients with gastrointestinal stromal tumor (GIST) who were treated at a single institution and followed up prospectively.Summary Background DataA GIST is a visceral sarcoma that arises from the gastrointestinal tract. Surgical resection is the mainstay of tre

https://ink.library.smu.edu.sg/cgi/viewcontent.cgi?article=1016&context=soe_research

Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastroin- testinal (GI) tract. They are defined here as KIT (CD117, stem cell factor receptor)-positive mesenchymal spindle cell or epithelioid neoplasms primary in the GI tract, omentum, and mesentery. GISTs typically present in old- er individuals and are most common in the stomach (60-70%), followed by small intestine (20-25%), colon and rectum (5%), and esophagus (<5%). Benign tumors outnumber the malignant ones by a wide margin. Ap- proximately 70% of GISTs are positive for CD34, 20-30% are positive for smooth muscle actin (SMA), 10% are positive for S100 protein and <5% are positive for desmin. The expression of CD34 and SMA is often reciprocal. GISTs commonly have activating mutations in exon 11 (or rarely exon 9 and exon 13) of the KIT gene that encodes a tyrosine kinase receptor for the growth factor named stem cell factor or mast cell growth factor. Ligand-independent activation of KIT appears to be a strong candidate for molecular pathogenesis of GISTs, and it may be a target for future treatment for such tumors. Other genetic changes in GISTs discovered using comparative genomic hybridization include losses in 14q and 22q in both benign and malignant GISTs and occurrence in various gains predominantly in malignant GISTs. GISTs have phenotypic similarities with the in- terstitial cells of Cajal and, therefore, a histogenetic ori- gin from these cells has been suggested. An alternative possibility, origin of pluripotential stem cells, is also possible; this is supported by the same origin of Cajal cells and smooth muscle and by the common SMA ex- pression in GISTs. GISTs differ clinically and pathoge- netically from true leiomyosarcomas (very rare in the GI tract) and leiomyomas. The latter occur in the GI tract, predominantly in the esophagus (intramural tumors) and the colon and rectum (muscularis mucosae tumors). They also differ from schwannomas that are benign S100-positive spindle cell tumors usually presenting in the stomach. GI autonomic nerve tumors (GANTs) are probably a subset of GIST. Other mesenchymal tumors that have to be separated from GISTs include inflamma- tory myofibroblastic tumors in children, desmoid, and dedifferentiated liposarcoma. Angiosarcomas and meta- static melanomas, both of which are often KIT-positive, should not be confused with GISTs.

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Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis.

The interstitial cells of Cajal (ICC) form a complex cell network within the gastrointestinal tract wall where they function as a pacemaker system. Expression of the kit proto-oncogene is essential for the development of this system. The aim of our study was to examine the hypothesis that gastrointestinal stromal tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58 stromal tumors were characterized and found to share many features with ICC. Seventy-eight stromal tumors were immunophenotyped, particularly with regard to the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal hyperplasia and hypertrophy of kit receptor positive cells were also observed in the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed in interstitial cells surrounding Auerbach's ganglia suggests that a subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas and leiomyosarcomas, were all negative for the kit receptor. We conclude that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype. We propose that the noncommittal name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker cell tumor.

Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal.

Two deceptively benign-appearing, unclassifiable but very similar fibromyxoid sarcomas characterized histologically by bland, innocuous-appearing fibroblastic cells and a swirling, whorled growth pattern are presented. The tumors both occurred in women in their late twenties and were located in the soft tissues of the scapular area and the axillary-chest wall area, respectively. Lung metastases developed in both cases; one patient died 94 months after excision of the primary neoplasm, whereas the other was alive at 82 months. The designation "low-grade fibromyxoid sarcoma" is suggested for these tumors.

Low-grade Fibromyxoid Sarcoma. A Report of Two Metastasizing Neoplasms Having a Deceptively Benign Appearance

M. D. Anderson Hospital cases diagnosed as adenocarcinoma of minor salivary glands before 1977 were reviewed. Within this heterogeneous group of neoplasms there was identified one clinicopathologic tumor entity, which we have designated "polymorphous low-grade adenocarcinoma." The 14 tumors in that category were characterized by cytologic uniformity and histologic diversity; growth patterns varied (both within and among cases) from solid to tubular to papillary to cribriform (pseudoadenoid cystic) to fascicular, while the cells were always small to medium-sized, regular, and lacking in nuclear atypia. Mitotic figures were infrequent, and tumor necrosis was seen in only one instance (a recurrent neoplasm). Clear cytoplasm, oxyphilic and mucinous metaplasia, and intratubular calcification were sometimes present, and stromal mucinization and hyalinization were common. The tumors were always unencapsulated, and exhibited extension into surrounding tissues including bone. The 14 patients ranged in age from 27 to 76 years (median, 64 years). Eight were male and six were female; eight were white and six were black. The neoplasm was intraoral in all cases, involving the palate in 11, the buccal mucosa in two, and the posterior mandibular area in one. Local recurrence developed in one case, cervical lymph node metastasis in one, and both recurrence and cervical lymph node metastasis in two. The number of successive recurrences ranged up to three, and the interval to recurrence varied up to nine years (the interval to metastasis up to five years). Although radical surgical procedures were necessary for tumor control in some cases, no distant metastases occurred and all patients were clinically tumor-free at latest follow-up.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819840215%2953%3A4%3C935%3A%3AAID-CNCR2820530420%3E3.0.CO%3B2-V

Polymorphous low-grade adenocarcinoma of minor salivary glands. A study of 14 cases of a distinctive neoplasm.

Cases of gastrointestinal smooth muscle tumor seen at M. D. Anderson Hospital and followed for a minimum of 10 years are presented. The tumors were classified as high-grade leiomyosarcoma (41 cases), low-grade leiomyosarcoma (13 cases), and leiomyoma (2 cases). All of the leiomyosarcomas originated in the stomach (21 cases), small intestine (29 cases), or rectum (4 cases) and appeared to have arisen from the muscularis propria. Leiomyosarcomas were considered high-grade when the maximal mitotic rate in ten consecutive high-power fields was ten or more and low-grade when this rate was lower (actual maximal rates in the low-grade group varied from 1-5/10 high-power fields). All patients with high-grade leiomyosarcoma died of tumor after intervals ranging from 5 to 90 months (median, 25 months). All but two with low-grade leiomyosarcoma also died of tumor, but frequently after much longer intervals (range, 42-221 months; median, 98 months; survival difference P = 0.002). Intervals to recurrence and metastasis were correspondingly longer in the low-grade group (up to 188 months). The two leiomyomas were small (less than 2 cm), had no mitotic figures, and were less cellular than any of the leiomyosarcomas. However, they both occurred in locations in which no leiomyosarcomas were seen (muscularis propria of the esophagus and muscularis mucosae of the rectum); therefore, the problem of distinguishing leiomyomas from leiomyosarcomas in sites where the latter did arise could not be resolved, particularly in view of the fact that fatal low-grade leiomyosarcomas had diameters as small as 1 cm and maximal mitotic rates as low as one per ten high-power fields. "Leiomyoblastoma" was not found to be an entity; it is recommended that this term be dropped.

Smooth muscle tumors of the gastrointestinal tract. A study of 56 cases followed for a minimum of 10 years.

Sixty-nine cases of mucoepidermoid carcinoma with a minimum of five years follow-up are presented. Major salivary glands were involved in 46 cases (44 parotid, two submandibular), and intraoral minor glands in 23. The tumor was considered histologically high grade (20 cases) when 90% or more of its area was made up of tumor cells and 10% or less of intracystic space and low grade (49 cases) when this ratio was lower. The proportion of cell types was not considered in grading: although intermediate, epidermoid, and clear cells usually predominated in high-grade tumors, several such examples contained numerous mucous cells. Grade was highly significant prognostically; all but 2 of the 14 deaths due to tumor and all six instances of distant metastasis occurred in cases with high-grade tumors. High histologic grade also was associated with an increased incidence of local recurrence (particularly recurrence not subsequently controlled) and cervical lymph node metastasis; in the case of recurrence this was due in part to the fact that inadequate surgical margins were more common with high-grade tumors. Tumors measuring less than 2.5 cm were rarely fatal regardless of grade, there being only two such deaths (one high grade, one low grade). Nuclear anisochromia and pleomorphism of more than slight degree, frequent mitoses, and tumor necrosis of more than focal extent were found to be untypical of mucoepidermoid carcinoma regardless of grade; these findings should occasion consideration of other diagnoses such as poorly differentiated adenocarcinoma with a solid growth pattern and adenosquamous carcinoma.

Mucoepidermoid carcinoma of salivary glands: a study of 69 cases with special attention to histologic grading.

Thirty-seven cases of uterine leiomyosarcoma are presented, along with nine cases of leiomyoma variants from which they were distinguished. All patients were followed for a minimum of 10 years. In cases with nuclear pleomorphism, leiomyosarcoma was diagnosed when there were five or more mitotic figures in ten consecutive high-power (±400) fields in the most active area of the tumor, and also when there were fewer mitotic figures but extensive tumor necrosis (there was only one leiomyosarcoma without nuclear pleomorphism, and it had more than 20 mitotic figures in ten high-power fields). Tumor size was the major prognostic factor in the leiomyosarcoma group; five of eight patients with neoplasms measuring less than 5 cm in maximum dimension survived, whereas no patient with a larger tumor did so. Other pathologic and clinical variables, including mitotic rate, tumor necrosis, degree of nuclear pleomorphism, vascular invasion, and patient age, had no significant relationship to survival or tumor behavior in leiomyosarcoma when tumor size was taken into account. The nine cases of leiomyoma variants consisted of three atypical leiomyomas (which had nuclear pleomorphism, one or no mitotic figures per ten high-power fields, and no necrosis), two plexiform leiomyomas, two cases of peritoneal leiomyomatosis, one palisaded leiomyoma, and one case of intravenous leiomyomatosis; all of these patients were tumor-free on follow-up.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/1097-0142%2819881115%2962%3A10%3C2239%3A%3AAID-CNCR2820621028%3E3.0.CO%3B2-Y

Harry L. Evans

Papers

Low-grade Fibromyxoid Sarcoma. A Report of Two Metastasizing Neoplasms Having a Deceptively Benign Appearance

Polymorphous low-grade adenocarcinoma of minor salivary glands. A study of 14 cases of a distinctive neoplasm.

Smooth muscle tumors of the gastrointestinal tract. A study of 56 cases followed for a minimum of 10 years.

Mucoepidermoid carcinoma of salivary glands: a study of 69 cases with special attention to histologic grading.

Smooth muscle neoplasms of the uterus other than ordinary leiomyoma. A study of 46 cases, with emphasis on diagnostic criteria and prognostic factors.