Primary uterine endometrial stromal neoplasms. A clinicopathologic study of 117 cases

We present the results of a clinicopathologic study of 109 patients with endometrial stromal sarcoma and eight patients with endometrial stromal nodule. Of the 109 patients with endometrial stromal sarcoma, follow-up was obtained on 93 (85%). The stage distribution of the patients with stromal sarcoma and the number of patients with follow-up (numerator) compared to the total number of patients in each stage (denominator) are: Stage 1, 73/85; Stage II, 3/6; Stage III, 11/11; Stage IV, 6/7. Stage II patients are considered separately in the analysis. Thirty-six percent of the Stage I patients experienced one or more relapses. Of these, six (23%) died of disease from 11 to 360 months from diagnosis (median, 79 months). Nine (35%) were alive with disease. Of the eleven Stage III patients, eight had one or more relapses and of these, six died of disease. Of the six Stage IV patients, five had one or more relapses and of these, three died of disease. The outcome differences between Stages I, III, and IV are statistically significant (p less than .01). Microscopic features evaluated included the mitotic index (MI = number of mitoses/10 high-power fields) and cytologic atypia. Forty-five percent of Stage I patients who had both rare mitotic figures and minimal atypia had one or more relapses and of these, two (13%) died of disease at 85 and 360 months, respectively. Thus, neither MI nor cytologic atypia were predictive of tumor recurrence for patients with Stage I tumors.     

乳腺癌间质成纤维细胞的平滑肌分化及意义

目的　观察乳腺癌间质成纤维细胞平滑肌分化情况 ,评价临床病理学意义。方法　对69例乳腺癌标本进行α SMA免疫组织化学染色 ,以 8例无癌区域乳腺组织 (距癌肿边缘 5cm以上 )为对照 ,分析浸润性乳腺癌间质成纤维细胞平滑肌分化与年龄、肿瘤大小、淋巴结转移、组织学分级和雌激素受体状态的关系。结果　无癌区域乳腺组织和原位癌间质无成纤维细胞平滑肌分化现象 ,5 5 .5 %的浸润性乳腺癌间质成纤维细胞有α SMA阳性表达 (P <0 .0 5 ) ;68.3 % ( 2 8/ 41)的淋巴结转移病例出现间质成纤维细胞平滑肌分化 ,且明显高于无淋巴结转移者 ( 2 6.3 % ,P <0 .0 5 ) ;组织学Ⅱ ,Ⅲ级的浸润性乳腺癌间质成纤维细胞平滑肌分化 ( 2 6/ 3 9)明显多于组织学Ⅰ级 ( 7/ 2 1,P <0 .0 5 )。结论　间质成纤维细胞平滑肌分化与乳腺癌的浸润和恶性程度有关 ,肌成纤维细胞可能在乳腺癌的浸润和转移中发挥重要的旁分泌作用。     

h-Caldesmon expression effectively distinguishes endometrial stromal tumors from uterine smooth muscle tumors

Distinction of endometrial stromal neoplasms from cellular smooth muscle tumors of the uterus is sometimes difficult. Immunohistochemistry is often not helpful because muscle actins and desmin are expressed in both neoplasms. This study's goal was to determine whether h-caldesmon, a smooth muscle-specific isoform of a calcium, calmodulin, and actin binding protein, could effectively distinguish endometrial stromal tumors from uterine smooth muscle tumors. The authors analyzed immunohistochemical expression in 24 endometrial stromal neoplasms (21 sarcomas and three nodules), 29 leiomyosarcomas, 32 leiomyomas (10 "usual," 14 cellular leiomyoma, and eight "highly cellular" types), 40 myometria, and 25 endometria. h-Caldesmon was diffusely positive in all myometria, leiomyomata, and leiomyosarcomas. Of note, 16 leiomyosarcomas (55%) were positive for h-caldesmon in more than 50% of tumor cells. In five "highly cellular" leiomyomas, h-caldesmon expression was markedly decreased or absent in areas morphologically resembling endometrial stromal tumors, raising the possibility that these tumors may be mixed smooth muscle-endometrial stromal neoplasms. In contrast, h-caldesmon expression was absent in all endometria and endometrial stromal neoplasms apart from accompanying small vessels. Desmin was diffusely positive in all myometria and leiomyomata. The fraction of cells expressing desmin was greater than that of h-caldesmon in only 10% of leiomyosarcomas. Focal desmin expression was also present in eight of 25 (32%) endometria and 12 of 24 (50%) endometrial stromal neoplasms. h-Caldesmon appears to be a more sensitive and specific marker of smooth muscle differentiation in the uterus than desmin and may be a useful tool for distinguishing and classifying uterine mesenchymal tumors.     

An immunohistochemical analysis of endometrial stromal and smooth muscle tumors of the uterus: a study of 54 cases emphasizing the importance of using a panel because of overlap in immunoreactivity for individual antibodies

The expression of desmin, h-caldesmon, calponin, CD10, CD34, CD99, inhibin, and keratin (AE1/3-Cam 5.2) was studied in 10 conventional leiomyomas, 9 highly cellular leiomyomas, 9 epithelioid smooth muscle tumors, 9 leiomyosarcomas, 10 endometrial stromal tumors (4 with smooth muscle metaplasia), and 7 uterine tumors resembling ovarian sex cord tumors (UTROSCTs). c-kit expression was tested in 10 endometrial stromal tumors, 7 UTROSCTs, and 9 leiomyosarcomas. Desmin was positive in almost all smooth muscle tumors except those of epithelioid type, which were positive in only about half of the cases. It also stained areas of smooth muscle differentiation in endometrial stromal tumors and five of seven UTROSCTs. h-caldesmon was positive in almost all nonepithelioid smooth muscle tumors and in areas of smooth muscle differentiation in endometrial stromal tumors; it was positive in only about half of the epithelioid smooth muscle tumors and negative in all UTROSCTs. Calponin was positive in most tumor types. CD10 was positive in nine of 10 endometrial stromal tumors and five of seven UTROSCTs, although very focally in the latter group. It was also expressed, however, in almost all leiomyosarcomas, almost 50% of highly cellular leiomyomas, and rarely in the other smooth muscle tumors. CD34 was negative in the tested tumors with rare exceptions. CD99 and inhibin were positive in four of seven and one of seven UTROSCTs. Keratin positivity was found in most (five of seven) UTROSCTs and occasionally in smooth muscle tumors (seven of 37). c-kit was negative in all endometrial stromal tumors, UTROSCTs, and leiomyosarcomas. The major conclusions of this study are as follows: 1) Pure endometrial stromal tumors are usually desmin negative. 2) In contrast to some previous studies, CD10 expression was often seen in smooth muscle tumors, including most leiomyosarcomas and almost half of highly cellular leiomyomas. As a result, a panel of CD10, h-caldesmon, and desmin should be used and will distinguish endometrial stromal tumors from highly cellular leiomyomas in most cases. 3) In contrast to a previous study, no significant differences in immunoreactivity were seen between h-caldesmon and desmin in tumors with smooth muscle differentiation. 4) The absence of h-caldesmon in UTROSCTs helps separate them from epithelioid smooth muscle tumors. 5) UTROSCTs may express epithelial, stromal, and smooth muscle markers, suggesting divergent differentiation. 6) Our study shows less frequent inhibin expression in the sex cord-like elements of the UTROSCTs than in other studies. 7) c-kit may help distinguish metastatic endometrial stromal tumors of the uterus (c-kit negative) from gastrointestinal stromal tumors (c-kit positive). 8) CD34, CD99, and keratin have no or minimal role in this area, but keratin positivity in smooth muscle tumors should not lead to their confusion with epithelial tumors.     

The immunohistochemistry of gastrointestinal stromal tumors. Evidence supporting an origin from smooth muscle

To study the histogenesis of gastrointestinal stromal tumors, 79 cases were evaluated for desmin (DES), vimentin (VIM), and S-100 protein immunoreactivity by the avidin-biotin immunoperoxidase procedure on paraffin-embedded, Bouin's-fixed tissue sections. All tumors showed weak vimentin positivity. Trapped non-neoplastic smooth muscle and nerve twigs were often noted, particularly at the tumor periphery. Significant tumor S-100 positivity was not identified in our series. Similarly, glial fibrillary acidic protein (GFAP) immunoreactivity (performed in 11 desmin-negative tumors) was not detected within either gastrointestinal stromal tumors or enteric glial cells. Fifty-three percent (53%) of all gastrointestinal stromal tumors (GIST) displayed positive tumor cell desmin immunoreactivity. All 10 esophageal and all four colorectal tumors were diffusely desmin positive and unequivocal smooth muscle lesions. In contrast, only 17 of 37 (46%) benign and six of nine (67%) malignant gastric tumors were desmin positive. Similarly, four of 10 (40%) benign and one of nine (11%) malignant small-bowel tumors expressed desmin. Several gastric neoplasms with prominent nuclear palisading resembling schwannian Antoni A regions were nonetheless desmin positive. Epithelioid gastric tumors were more frequently desmin positive than nonepithelioid tumors; however, this positivity did not attain statistical significance. Two gastrointestinal stromal tumors that were desmin negative in paraffin-embedded material had detectable antigen in frozen sections. Gastric and small-bowel tumors measuring less than 3 cm were significantly more often desmin positive than those 3 cm or greater. We conclude that the method of fixation, tissue preparation, and immunostaining may significantly affect the expression of desmin. Although the histogenesis of gastrointestinal stromal tumors remains controversial, most of these tumors show evidence of smooth muscle differentiation.     

Use of oxytocin receptor expression in distinguishing between uterine smooth muscle tumors and endometrial stromal sarcoma

The present study aimed to investigate oxytocin receptor (OTR) expression in the normal uterus, and particularly in uterine smooth muscle tumors and endometrial stromal sarcomas (ESSs) because these tumors can be difficult to distinguish. The expressions of OTR, CD10, h-caldesmon, calponin, smooth muscle actin, and desmin were analyzed in 10 conventional leiomyomas (LMs), 10 highly cellular leiomyomas (HCLs), eight leiomyosarcomas (LMSs), and nine ESSs. In five normal uteri and five cases of adenomyosis, OTR was strongly expressed in the myometrium and showed expression pronounced in the surface epithelium during the late proliferative phase and at the time of ovulation, whereas the endometrial stromal cells were negative. All LMs and HCLs were strongly positive for OTR. Five cases of LMS showed moderate to strong OTR expression in 100% of the tumor cells, whereas three cases were weakly positive in 10-20% of the tumor cells. Every ESS was negative for OTR, except in regions of smooth muscle differentiation. All ESSs were positive for CD10, as were one LM, six HCLs, and five LMSs. The ESSs were negative for h-caldesmon and showed desmin positivity mainly in regions of smooth muscle metaplasia. h-Caldesmon, calponin, smooth muscle actin, and desmin were expressed in all LMs, HCLs, and LMSs except for one leiomyosarcoma with epithelioid features, which was negative for h-caldesmon and calponin. Our study indicates that the evaluation of OTR expression is useful in the distinction of uterine smooth muscle tumors from ESSs, and that the OTR is expressed in normal and neoplastic uterine smooth muscle cells.     

Perspectives on pure ovarian stromal neoplasms and tumor-like proliferations of the ovarian stroma

In this study, we discuss the advances in our knowledge of the pathology of pure ovarian stromal neoplasms and discuss tumor-like conditions of ovarian stroma that can mimic ovarian stromal neoplasms clinically, macroscopically, or histologically. This review emphasizes recent studies and those that have significantly advanced our knowledge in the past. The neoplasms in this group occur over a wide age range and are often unilateral. In difficult cases, immunocytochemistry provides improved diagnostic accuracy. The most useful antibodies in this regard are inhibin and calretinin that are positive in most tumors and tumor-like proliferations in the ovarian stromal category. Steroidogenic factor 1 is a promising new marker that has not yet been completely validated. Recent studies of tumors in the fibroma-thecoma group suggest that nuclear atypia is more significant than mitotic activity in the assessment of the biological behavior of these neoplasms. Wherever applicable, we discuss molecular techniques that are currently diagnostically useful.     

Eccrine and squamous differentiation in Merkel cell carcinoma. An immunohistochemical study

Of the 42 Merkel cell carcinomas that we studied, two showed numerous tubular structures within sheets and nests of small cells. The small cells stained for both neuron-specific enolase and keratin. The keratin decorated a dot-like paranuclear structure. The ducts stained positively for carcinoembryonic antigen (CEA) and CF-1 (cystic fibrosis-1, a monoclonal antibody that only stains eccrine duct and acrosyringium). Electron microscopy performed on one case showed cytoplasmic dense-core neurosecretory granules and intercellular lumina lined by cells containing microvilli. These ultrastructural and immunohistochemical features support the concept of eccrine differentiation in these tumors. A third case contained foci of typical keratinizing squamous cell carcinoma admixed with sheets of small cells. The immunohistochemical and ultrastructural characteristics of this tumor were essentially similar to those of a conventional Merkel cell carcinoma. Our findings suggest that Merkel cell carcinomas, similar to neuroendocrine tumors from other anatomic sites arise from a primitive totipotential stem cell that has the capacity to differentiate along different cell lines.     

Single-stage resection of a mixed endometrial stromal sarcoma and smooth muscle tumor with intracardiac and pulmonary extension

A case of mixed endometrial stromal sarcoma and smooth muscle cell tumor of the uterus with intravenous extension into the right heart and pulmonary artery is presented. The current literature and diagnostic and therapeutic strategies of pelvic tumors with intravenous extension are reviewed.     

Gastrointestinal stromal tumors/smooth muscle tumors (GISTs) primary in the omentum and mesentery: clinicopathologic and immunohistochemical study of 26 cases.

Gastrointestinal stromal tumor or smooth muscle tumor (GIST) is the designation for a major subset of gastrointestinal mesenchymal tumors that histologically, immunohistochemically, and genetically differ from typical leiomyomas, leiomyosarcomas, and schwannomas. Because GISTs, like the interstitial cells of Cajal, the gastrointestinal pacemaker cells, express CD117 (c-kit protein), the origin of GISTs from the interstitial cells of Cajal has been recently proposed. Comparison of GISTs primary in the omentum and mesentery to GISTs primary in the tubular gastrointestinal tract is of particular diagnostic and histogenetic interest in view of the possible similarity of these tumors with the GIST group. In this study, we analyzed 14 omental and 12 mesenteric primary mesenchymal tumors representing smooth muscle tumors or GISTs. These tumors were phenotypically compared with gastric and small intestinal GISTs, leiomyomas of the esophagus, and leiomyosarcomas of the retroperitoneum. Most (13 of 14) omental and mesenteric (10 of 12) tumors showed histologic features similar to GISTs with elongated spindle cells or epithelioid cells with high cellularity; most of these tumors showed low mitotic activity. Omental and mesenteric GISTs were typically positive for CD117 and less consistently for CD34. They often showed alpha-smooth muscle actin reactivity but were virtually negative for desmin and S-100 protein. One omental and two mesenteric tumors showed features of leiomyosarcoma with ovoid, less elongated nuclei, cytoplasmic eosinophilia; all these tumors had significant mitotic activity. These tumors were positive for alpha-smooth muscle actin and two of them for desmin, but all were negative for CD34 and CD117, similar to retroperitoneal leiomyosarcomas. Tumor-related mortality occurred in the group of mesenteric GISTs, but not in the group of omental GISTs. In contrast, all three patients with a true leiomyosarcoma of the omentum or mesentery had documented liver metastases or died of tumor. In summary, we show that tumors phenotypically identical with GISTs occur as primary tumors in the omentum and mesentery. The occurrence of CD117-positive tumors outside the gastrointestinal tract militates against an origin of these tumors exclusively from the interstitial cells of Cajal.     

Atypical stromal smooth muscle hyperplasia of prostate

A prostatic lesion was resected but recurred six years later with the same atypical smooth muscle hyperplasia in the stroma and without glandular atypia. Ultrastructural study confirms the smooth muscle origin and its atypicality. Review of previous reports of leiomyosarcoma of the prostate show that the minimum criteria for malignancy are gross evidence of capsular invasion and one to two mitotic figures per ten high-power field. Cellular pleomorphism and cellularity by themselves are insufficient to diagnose sarcoma.     

Neuroendocrine differentiation in hepatoblastoma. An immunohistochemical investigation

Hepatoblastoma exhibits a wide range of epithelial and mesenchymal lines of differentiation. Neuroendocrine differentiation in this tumor has not previously been reported. We investigated seven hepatoblastomas of different subtypes (five pure epithelial hepatoblastomas, including one small-cell hepatoblastoma, and two mixed hepatoblastomas) using a broad panel of antibodies against epithelial, mesenchymal, neural, and neuroendocrine markers, alpha-1-antitrypsin (alpha 1-AT), alpha-1-antichymotrypsin (alpha 1-ACT), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), serotonin, and 14 regulatory peptides. Chromogranin A-immunoreactive neuroendocrine tumor cells, some of which also exhibited immunoreactivity for serotonin and somatostatin, were found in the fetal and embryonal parts of the mixed hepatoblastomas. The osteoid-like material in the mixed hepatoblastomas contained cells with immunoreactivity for chromogranin A, neuron-specific enolase, keratin, and alpha 1-AT, alpha 1-ACT, AFP, and CEA, in addition to S-100 protein and vimentin. Parallels to the neuroendocrine differentiation in hepatoblastomas are found in tumors of the gastrointestinal tract and bronchopulmonary tree. These tumors may also exhibit a neuroendocrine component; that is, multidirectional differentiation may occur, as in hepatoblastoma. The immunoreactivity of some of the cells of the osteoid-like material for keratin, alpha 1-AT, alpha 1-ACT, AFP, CEA, and chromogranin A suggests that these cells--and probably the surrounding material--are of epithelial origin.     

An electrophysiological study of the smooth muscle of the human colon.

Electrical recordings were made in vitro from preparations of human colonic smooth muscle from surgically resected specimens. The behaviour of the taenia consisted of regular spike action potentials based on a slow wave rhythm (22 +/- 5 c.p.m.), with tetanic contractions of the muscle. The actions of cholinergic drugs were studied and experiments performed to investigate the mechanism of the action potentials. The circular muscle produced clusters of spikes with solitary contractions. The differences between the two muscle layers may be of relevance to understanding the colonic electromyogram as recorded in vivo.     

胃肠道间质细胞瘤临床病理与免疫组化研究

目的　探讨胃肠间质瘤 (GISTs)的临床病理和免疫组化特征 ,为其诊断提供参考指标。方法　对 3 5例GISTs进行病理形态学观察 ,并采用免疫组化染色检测其CD1 1 7、CD3 4、vimentin、SMA和S-1 0 0蛋白表达检测。结果　 3 5例GISTs中 ,良性 1 6例 ,恶性 1 7例 ,潜在恶性 2例 ,主要由梭形细胞和上皮样细胞构成。免疫组化vimentin、CD3 4、CD1 1 7肿瘤细胞显示明显阳性 ,阳性率分别为 1 0 0 %、88 6%、60 0 % ,SMA和S -1 0 0蛋白呈散在细胞阳性 ,阳性率分别为 3 4 3 %和 6 1 %。结论　GISTs是胃肠道最常见的间质肿瘤 ,HE染色下形态与平滑肌肿瘤和神经源性肿瘤较相似 ,免疫组化染色对其诊断和鉴别诊断具有重要作用 ,CD1 1 7特异性较高 ,CD3 4敏感性较高     

Primary smooth muscle tumor of the liver encasing hepatobiliary cystadenoma without mesenchymal stroma.

We describe a 59-year-old Japanese woman with a large mass of her liver encasing cystic components. Radiologic imaging showed the mass to be hypervascular, and surgical resection disclosed a white tumor. The solid portion was immunohistochemically characterized as a smooth muscle tumor. The cystic components were multilocular and lined with columnar epithelium, consistent with a hepatobiliary cystadenoma. The epithelium strongly stained for CA19-9. The subepithelial space was occupied by collagenous connective tissue interspersed with a small number of spindle-shaped cells. The cystic lesions lacked the mesenchymal stroma between the epithelium and connective tissue layer. There have been no previous reports of a hepatic smooth muscle tumor encasing a hepatobiliary cystadenoma. Because of the pathogenesis of the cystadenoma, it is possible to assume that the smooth muscle tumor also arose from the cells composing the biliary duct in association with the development of the cystadenoma.     

Pulmonary metastases in patients with low-grade endometrial stromal sarcoma. Clinicopathologic findings with immunohistochemical characterization

Two cases of low-grade endometrial stromal sarcoma (ESS) presenting as cystic pulmonary metastases are reported. Both lung lesions were initially thought to represent examples of so-called mesenchymal cystic hamartoma. A diligent search of the past medical records in the first case revealed that a primary low-grade ESS of the uterus had been resected 27 years earlier. In the second case, a uterine tumor was seen by computed tomography scan and subsequent pathologic examination of the hysterectomy specimen established the presence of a low-grade ESS. Peritoneal metastases, present in both cases, also presented diagnostic problems until the uterine primaries were recognized. Immunoreactivity for desmin was detected in all primary and metastatic tumor sites examined. We conclude that ESS should be included among the desmin-positive spindle cell sarcomas and that metastatic ESS should be included in the differential diagnosis of "benign" mesenchymal cystic hamartoma of the lung.     

Patterns of stromal elements in an implanted ureteric transitional cell carcinoma. An immunohistochemical and ultrastructural study

The results of the study of three implanted ureteric tumors from a primary transitional cell carcinoma of the renal pelvis are reported. Using both light microscopic immunohistochemistry and transmission electron microscopy, the stroma of the tumor showed consistent evidence for the production of at least its collagenous component by the neoplastic cells. Our findings argue with the notion that occasional fibroblasts and other cells of mesenchymal origin could play a major role in this phenomenon. Therefore, it seems plausible to suggest that what is happening in these tumors is similar to the behavior of malignant cells in scirrhous 'infiltrating' carcinoma of the breast and other sites.