Jejunal stromal tumor with skeinoid fibers or myenteric plexoma: A case report

Small Intestinal stromal tumors with 'skeinold fibers' are uncommon stromal tumors with an associated controversial histogenesis. Although their microscopic appearance Is suggestive of a smooth muscle nature, they lack specific smooth muscle features, as evident by electron microscopy and Immunohistochemistry. They also appear to lack features of neurogenic origin because they fail to react with neural/neuroendocrine markers such as S-100 protein, neuronapecific enolase and chromogranin. It is interesting, nonetheless, to note that the ultrastructural examination of these tumors may show structures reminiscent of neural differentiation, such as cytoplasmic projections, containing occasional membrane-bound, densecore, neurosecretory type granules, which mimick the long cytoplasmic processes seen In tumors of neural origin. Moreover, the association of these tumors with Von Recklinghausen's neurofibromatosis, as well as the presence of 'skeinoid fibers' in proven neurogenic spindle cell neoplasms such as gastrolntestinal autonomic nerve tumors and schwannomas, suggests that these tumors might also be neurogenic In origin and enhances the diagnostic value of 'skeinold fibers' as a possible ultrastructural marker of neural differentiatioin. Thus, light microscopic evaluation is clearly Insufficient to accurately diagnose these tumors and to determine their histogenesis, electron microscopic and Immunohistochemical studies being neccesary. In this article the histogenesis of small Intestinal stromal tumors with 'skeinold fibers', regarding a jelunal neoplasm In a 63-yearsld patient, is reviewed. The light microscopic, immunohistochemical and ultrastructural features are described and compared with findings usually seen in all those stromal tumors which may raise a differential diagnosis, such as smooth muscle stromal tumors, gastrointestinal autonomic nerve tumors, schwannomas, paragangliomas and fibrosarcomas.     

Letter to the Editor Ciliary Hypoplasia: A Rare Cause of Ciliary Dyskinesia

The signet-ring stromal tumor of the ovary, described only twice previously, is an enigmatic lesion in respect to its cell lineage and the nature of the cytoplasmic vacuoles that cause the signet-ring cell appearance. The vacuoles were shown in the initial report to contain no lipid, mucoprotein, or glycogen, and the ovarian stromal cell was assumed to be the cell of origin. The present study describes three ovarian neoplasms in which the immunohistochemical and ultrastructural findings support a stromal origin for the cells, and a fourth tumor that simulated the other three closely on light microscopic examination but had several features supporting a sex-cord rather than stromal origin: immunohistochemical staining for keratin and alpha smooth muscle actin, and globular keratin staining, similar to that seen in granulosa cell tumors; and numerous prominent junctions including desmosomes on electron microscopy. In only one of the four tumors were the vacuoles similar ultrastructurally to those in the first reported case, appearing to result from generalized edema of the cytoplasmic matrix. In a second tumor, the vacuoles resulted from hydropic swelling of numerous mitochondria, which filled the cytoplasm of the cells. In the other two tumors, the vacuoles were not cytoplasmic, but cytoplasmic pseudoinclusions of edematous extracellular matrix. An additional interesting finding in one of the four tumors was the presence of hyaline globules within and adjacent to the signet-ring cells. Ultra-structural examination revealed the globules to be degenerating erythrocytes, many of which had been phagocytosed by the tumor cells.     

Signet-Ring Stromal and Related Tumors of the Ovary

The signet-ring stromal tumor of the ovary, described only twice previously, is an enigmatic lesion in respect to its cell lineage and the nature of the cytoplasmic vacuoles that cause the signet-ring cell appearance. The vacuoles were shown in the initial report to contain no lipid, mucoprotein, or glycogen, and the ovarian stromal cell was assumed to be the cell of origin. The present study describes three ovarian neoplasms in which the immunohistochemical and ultrastructural findings support a stromal origin for the cells, and a fourth tumor that simulated the other three closely on light microscopic examination but had several features supporting a sex-cord rather than stromal origin: immunohistochemical staining for keratin and alpha smooth muscle actin, and globular keratin staining, similar to that seen in granulosa cell tumors; and numerous prominent junctions including desmosomes on electron microscopy. In only one of the four tumors were the vacuoles similar ultrastructurally to those in the first reported case, appearing to result from generalized edema of the cytoplasmic matrix. In a second tumor, the vacuoles resulted from hydropic swelling of numerous mitochondria, which filled the cytoplasm of the cells. In the other two tumors, the vacuoles were not cytoplasmic, but cytoplasmic pseudoinclusions of edematous extracellular matrix. An additional interesting finding in one of the four tumors was the presence of hyaline globules within and adjacent to the signet-ring cells. Ultra-structural examination revealed the globules to be degenerating erythrocytes, many of which had been phagocytosed by the tumor cells.     

Malignant stromal tumor, so called "gastrointestinal stromal tumor", with rhabdomyomatous differentiation occurring in the gallbladder

Gastrointestinal stromal tumors (GISTs) constitute the largest category of primary nonepithelial neoplasms of the gastrointestinal tract. It is extremely rare that this tumor occurs in the bile tract, and only a few cases have been reported. Immunohistochemically, the tumor cells revealed a phenotype similar to Cajal cells, occasionally with differentiation to smooth muscle cells or neural cells. We present a case of malignant stromal tumor similar to GISTs with rhabdomyomatous differentiation of the gallbladder in a 68-year-old woman. The resected tumor was predominantly composed of spindle cells with rhabdomyomatous differentiation. Immunohistochemical study revealed diffuse staining of tumor cells using vimentin despite negative staining for desmin or S-100. This indicated a mesenchymal origin of the cells without smooth muscle or neuronal differentiation. Myoglobin-positive cells, in which phosphotungstic acid hematoxylin staining revealed cross striations of the cytoplasm, suggested rhabdomyomatous differentiation. Diffuse positivity for KIT in the cells suggested that the pathogenesis of this tumor may resemble that of GIST. The tumor may have derived from a mesenchymal stem cell that had undergone partial rhabdomyomatous differentiation.     

十二指肠间质瘤的临床病理及免疫组织化学研究

目的：研究十二指肠间质瘤临床病理学特点和免疫组织化学表达特征。方法：对18例十二指肠间质瘤作了临床病理形态学观察和免疫组织化学分析。结果：18例肿瘤良性3例，恶性15例，基本细胞类型为梭形细胞，1例肿瘤细胞外基质可见丝团样纤维。免疫表型特征为：C-kit18例（100％）胞质强阳性表达；CD347例（38．9％）阳性；S－100蛋白9例（50％）呈局灶性或散在阳性，其中包括2例良性，7例恶性；SMA仅1例阳性。结论：十二指肠间质瘤恶性发生率较高，细胞类型以梭形细胞为主。C-kit因其敏感性高、特异性强成为十二指肠间质瘤的可靠标记物，但不能作为良恶性判断指标，CD34阳性表达率低；神经化生率较高平滑肌方向分化率低。     

Low-grade endometrial stromal sarcoma with intracardiac extension. Evolution of extensive smooth muscle differentiation and usefulness of immunohistochemistry for its recognition and distinction from intravenous leiomyomatosis.

This case, a rare example of low-grade endometrial stroma sarcoma with extensive smooth muscle differentiation which extended to the inferior vena cava and cardiac chambers closely resembling intravenous leiomyomatosis grossly and microscopically, illustrates the importance of extensive sectioning and the usefulness of immunohistochemistry. Although spindle cell components arranged in interlacing bundles consistent with smooth muscle differentiation were recognizable in the primary tumor (on retrospective review), extensive smooth muscle differentiation in the recurrent tumors masked prototypical morphologic features of stromal sarcoma and only small neoplastic stromal components were preserved in limited areas, leading to initial failure to distinguish the lesion from intravenous leiomyomatosis. The immunophenotyping disclosed two distinct cell populations in the tumor: i.e. vimentin-positive and smooth muscle marker negative stromal cells, and vimentin-negative spindle-shaped desmin-positive smooth muscle cells. Our observation suggests that the predominance of a smooth muscle component in such a tumor can be misleading and does not always warrant a diagnosis of intravenous leiomyomatosis, nor does it predict a benign clinical course. This case also provides an insight into the relationship of the endometrial stroma and myometrium, and their cell of origin and the histogenesis of endometrial stromal sarcoma.     

Hyaline globules in paucicellular leiomyomas of the gastrointestinal tract are distinct from skeinoid fibers and represent degenerating smooth muscle cells

Skeinoid fibers are globular, brightly eosinophilic periodic Schiff stain (PAS)-positive extracellular collagen deposits commonly seen in gastrointestinal stromal tumors (GIST) of the small bowel. However, smooth-surfaced hyaline globules are occasionally encountered in leiomyomatous GI neoplasms and may be mistaken for true skeinoid fibers. We investigated a total of 93 histologically and immunohistochemically well-characterized true smooth muscle neoplasms of the GI tract for the presence of hyaline globules. A variable number of PAS-positive intracellular and interstitial hyaline globules were detected in all benign paucicellular leiomyomas of the muscularis mucosae (n=72) and the muscularis propria (n=14) irrespective of tumor size and site, but in none of leiomyosarcomas (n=7) and cellular leiomyoma (n=1). In addition, similar findings were rarely seen in the adjacent muscularis propria. Similar to surrounding tumor cells, hyaline globules expressed desmin, α-SMA, and h-caldesmon, but were negative for CD117 and CD34. Ultrastructural examination revealed altered filamentous material in different stages of degeneration with variably condensed matrix and occasional peripheral condensation suggestive of calcification. True skeinoid fibers were not detected. The above findings are consistent with a multistep degenerative phenomenon affecting individual smooth muscle cells in paucicellular GI leiomyomas. Awareness of this finding would prevent misinterpretation as GIST, particularly in small biopsies.     

Gastrointestinal stromal tumor presenting as a recurrent vaginal mass

Gastrointestinal stromal tumors are CD117 (c-Kit)-positive mesenchymal neoplasms with histologic and ultrastructural features of the interstitial cell of Cajal. While tumors outside of the gastrointestinal tract have been described, to our knowledge the case we present is the first such case in the vagina. We describe a 75-year-old woman with a recurrent vaginal gastrointestinal stromal tumor without apparent rectal involvement. This tumor was characterized by short intersecting fascicles of spindled cells, focal necrosis, and 12 to 15 mitoses per 50 high-power fields. Immunohistochemistry revealed diffuse cytoplasmic positivity for CD117 (c-Kit), CD34, vimentin, and h-caldesmon. Tumor cells were negative for S100, desmin, actin, and CAM 5.2. The differential diagnosis in this case included a vaginal smooth muscle tumor. While histologically similar to a smooth muscle neoplasm, the immunohistochemical profile ruled out smooth muscle differentiation. Gastrointestinal stromal tumor should be considered in the differential diagnosis of vaginal mesenchymal neoplasms.     

Uterine endometrial stromal sarcoma with smooth muscle and glandular differentiation

This report describes a uterine tumour exhibiting areas of both endometrial stromal and smooth muscle differentiation. There was extensive intravascular permeation within the myometrium as well as extrauterine vascular involvement. The endometrial stromal component had a myxoid appearance and the smooth muscle component exhibited the typical features of intravenous leiomyomatosis. An additional feature was the presence of numerous benign endometrial-type glands within the neoplasm. In many areas a "zoning" phenomenon was present, with endometrial glands surrounded by endometrial stroma, which was in turn surrounded by smooth muscle. This unique combination of endometrial glands, endometrial stroma, and smooth muscle has, to the best of our knowledge, not been described previously and adds to the morphological spectrum of mixed endometrial stromal-smooth muscle tumours. This report discusses the differential diagnosis of this lesion, which has been designated a low grade endometrial stromal sarcoma with smooth muscle and glandular differentiation.     

Sinonasal Teratocarcinosarcoma: Ultrastructural and Immunohistochemical Evidence of Neuroectodermal Origin

The authors report a case of sinonasal teratocarcinosarcoma in a 37-year-old man, which was located in the anterior skull base and extended to the right nasal cavity and paranasal sinuses. The tumor was surgically resected twice, but it could not be removed completely. Microscopically, it was mainly composed of primitive cell nests within a moderately cellular stroma. The components of squamous cell epithelia with focal teratoid appearance and adenocarcinomatous differentiation were observed. There were many rhabdomyoblasts scattered in the nests and stroma. Ultrastructurally, the primitive cells had many neural processes with parallel microtubules, resembling olfactory neuroblastoma. Rhabdomyoblasts showed various degrees of skeletal muscle differentiation. Some of the stromal spindle cells had actin filaments with dense patches and dense core granules. Immunohistochemically, the primitive cells were positive for epithelial markers, neuron-specific enolase, synaptophysin, and myogenic regulatory proteins. The rhabdomyoblasts showed immunoreactivity for myoid markers, cytokeratin, epithelial membrane antigen, and synaptophysin. Most of the stromal spindle cells were positive for smooth muscle actin, neuron-specific enolase and synaptophysin. The immunohistochemical and ultrastructural findings suggest that primitive cells had the most primitive phenotype of placodes, and support the possibility that sinonasal teratocarcinosarcoma is essentially a neuroectodermal tumor with divergent differentiation.     

Renal angiomyolipoma resembling gastrointestinal stromal tumor with skenoid fibers

We report an unusual case of renal angiomyolipoma occurring in 68-year-old man. The tumor lacked well-developed vascular and adipose components and was composed almost exclusively of smooth muscle cells. Numerous skenoid-like periodic acid-Schiff-positive globules were interspersed between the tumor cells; the lesion therefore closely resembled a low-grade stromal tumor of the gastrointestinal tract. The HMB45-positive/CD34-negative immunophenotype was essential for the diagnosis of angiomyolipoma. Neither gastrointestinal tumor nor any signs of tuberous sclerosis were found. This lesion should be included in the list of morphologic variations of angiomyolipoma, which may cause diagnostic difficulties.     

胃肠道间质瘤的电镜和免疫组织化学研究

目的 探讨胃肠道间质瘤的组织起源和神经分化特征。方法 应用电镜和免疫组织化学对20例胃肠道间质瘤的超微结构和神经分化相关抗原表达进行研究。结果 20例胃肠道间质瘤c—kit表达均阳性。其中7例超微结构存在神经分化,12例未见神经或肌细胞分化,仅有1例存在向平滑肌纤维分化。神经分化形态表现为瘤细胞胞质和胞质突起内可见散在或簇状分布的致密核心颗粒,并形成突触样结构。并可见神经元样突起、饮液空泡和团丝样纤维。神经分化伴有致密核心颗粒病例在良性、交界性和恶性组各有1例、1例和5例。神经分化组病例神经分化相关抗原神经元特异性烯醇化菌、CD99、S—100和CD56阳性表达分别有7例、7例、5例和4例,均高于未定分化组。结论 胃肠道间质瘤和所谓的胃肠道自主神经肿瘤在组织形态和免疫表型都存在相互重叠现象,神经分化超微结构观察和神经分化相关抗原分析有助于确定胃肠道间质瘤的神经分化改变以及潜在的生物学行为。     

Sinonasal teratocarcinosarcoma: ultrastructural and immunohistochemical evidence of neuroectodermal origin

The authors report a case of sinonasal teratocarcinosarcoma in a 37-year-old man, which was located in the anterior skull base and extended to the right nasal cavity and paranasal sinuses. The tumor was surgically resected twice, but it could not be removed completely. Microscopically, it was mainly composed of primitive cell nests within a moderately cellular stroma. The components of squamous cell epithelia with focal teratoid appearance and adenocarcinomatous differentiation were observed. There were many rhabdomyoblasts scattered in the nests and stroma. Ultrastructurally, the primitive cells had many neural processes with parallel microtubules, resembling olfactory neuroblastoma. Rhabdomyoblasts showed various degrees of skeletal muscle differentiation. Some of the stromal spindle cells had actin filaments with dense patches and dense core granules. Immunohistochemically, the primitive cells were positive for epithelial markers, neuron-specific enolase, synaptophysin, and myogenic regulatory proteins. The rhabdomyoblasts showed immunoreactivity for myoid markers, cytokeratin, epithelial membrane antigen, and synaptophysin. Most of the stromal spindle cells were positive for smooth muscle actin, neuron-specific enolase and synaptophysin. The immunohistochemical and ultrastructural findings suggest that primitive cells had the most primitive phenotype of placodes, and support the possibility that sinonasal teratocarcinosarcoma is essentially a neuroectodermal tumor with divergent differentiation.     

Mixed endometrial stromal and smooth muscle tumor: Report of a case with focal anaplasia and early postoperative lung metastasis

A rare case of a mixed endometrial stromal and smooth muscle tumor arising in the uterus of a 74‐year‐old woman is reported. The patient underwent hysterectomy for an enlarging uterine mass, and a large intramural tumor, showing marked central hyaline necrosis with calcification, was found. The tumor consisted of an admixture of a low‐grade endometrial stromal sarcoma (ESS) and a fascicular proliferation of spindle cells suggesting smooth muscle differentiation, and a characteristic ‘star‐burst’ appearance was found. In the ESS region, there were a few small foci of anaplasia where large polygonal cells with atypical nuclei and abundant eosinophilic cytoplasm proliferated, and the proliferative activity was locally increased in these foci. A small metastatic nodule appeared in the lung nine months after the hysterectomy, and the resected metastatic lesion showed features of anaplastic spindle cell sarcoma which was immunoreactive for CD10 but not for smooth muscle markers. Mixed endometrial stromal and smooth muscle tumors should be regarded as malignant neoplasms with the potential for hematogenous metastasis, particularly when they contain foci of cellular anaplasia.     

Smooth Muscle Cell Abnormalities Associated with Gastric ECL Cell Carcinoids

The histologic and immunohistochemical study of 45 ECL cell gastric carcinoids and of the extratumoral gastric mucosa revealed four variants of smooth muscle cell abnormalities: (1) hypertrophy of muscularis mucosae trapped within the tumors, a finding occurring in 76.5% of cases; (2) proliferation of stromal smooth muscle cells originating from the muscularis mucosae and mostly associated with tumor invasion of the submucosa (seen in 93.9% of cases with abundant stromal component of the tumors); (3) occurrence of frequent, prominent aggregates of smooth muscle cells in the lamina propria of the antral (but not of the fundic) mucosa of the stomach (found in 41.7% of cases); and (4) increased thickness of the extratumoral muscularis mucosae in the fundic (but not in the antral) mucosa of patients with gastric carcinoids. In addition, localized muscle cell proliferation was also associated with foci of micronodular hyperplasia of endocrine cells in the extratumoral mucosa. These findings were neither observed in control cases of gastric adenocarcinoma, gastric peptic ulcer, and duodenal peptic ulcer (10 unselected cases from each group) nor were they observed in 10 subjects with normal gastric mucosa collected at autopsy. With the possible exception of the increased thickness of the extratumoral fundic muscularis mucosae, which may be influenced by the mucosal inflammatory process, it is suggested that the present findings represent a proliferative response of smooth muscle cells to basic fibroblastic growth factor whose production by gastric carcinoids and their precursor lesions has recently been demonstrated.     

Signet ring epithelioid stromal tumor of the small intestine

Cells having a signet ring appearance can occur in mesenchymal, lymphoid, and other nonepithelial neoplasms. We report the case of an intestinal stromal tumor with smooth muscle differentiation and a prominent signet ring cell component. The presence of signet ring forms of smooth muscle cells in sections of paraffin-embedded tissue often contrasts with a lack of cytoplasmic spaces by electron microscopy, and the ultrastructural finding of signet ring-like areas in the present case can be attributed to the fact that the tissue for electron microscopy was retrieved fromparaffin blocks where this peculiar artifact already existed. Ultrastructural examination of the signet ring-like areas suggests that they originated as retraction spaces which may have resulted from variations in intracellular tension forces related to the distribution of actin filaments.     

High‐grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation: Report of a case with cytomorphologic and immunocytologic analysis

We report a case of high‐grade endometrial stromal sarcoma with cytological and immunocytochemical findings. Cytologically, major tumor cells showed round‐to‐short spindle shapes with round‐ to oval‐shaped nuclei and moderately abundant delicate cytoplasm. Tumor cells with tapered shapes and eccentric nuclei were also observed. A few spindle cells having enlarged cigar‐shaped nuclei with conspicuous nucleoli and delicate wispy cytoplasm, which resembled leiomyosarcoma, were intermingled. One rhabdomyoblast cell with both α‐sarcomeric muscle actin and myoglobin was also observed. Most of the tumor cells, including the leiomyosarcomatous spindle cells, were positive for CD10, and negative for desmin and h‐caldesmon. Accordingly, when relatively monotonous round‐to‐short spindle tumor cells and taper‐shaped tumor cells are observed in the female genital tract, high‐grade endometrial stromal sarcoma should be considered in the differential diagnosis. Immunocytochemistry contributed to the correct diagnosis. This case was high‐grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.     

Undifferentiated (embryonal) sarcoma of the liver in middle-aged adults: smooth muscle differentiation determined by immunohistochemistry and electron microscopy

Undifferentiated (embryonal) sarcoma of the liver (UESL) is a rare pediatric liver malignancy that is extremely uncommon in middle-aged individuals. We studied 2 cases of UESL in middle-aged adults (1 case in a 49-year-old woman and the other in a 62-year-old man) by histology, immunohistochemistry, and electron microscopy to clarify the cellular characteristics of this peculiar tumor. One tumor showed a mixture of spindle cells, polygonal cells, and multinucleated giant cells within a myxoid matrix and also revealed focal areas of a storiform pattern in a metastatic lesion. The other tumor was composed mainly of anaplastic large cells admixed with few fibrous or spindle-shaped components and many multinucleated giant cells. In both cases, some tumor cells contained eosinophilic hyaline globules that were diastase resistant and periodic acid-Schiff positive. Immunohistochemically, the tumor cells showed positive staining for smooth muscle markers, such as desmin, alpha-smooth muscle actin, and muscle-specific actin, and also for histiocytic markers, such as alpha-1-antitrypsin, alpha-1-antichymotrypsin, and CD68. Electron microscope examination revealed thin myofilaments with focal densities and intermediate filaments in the cytoplasm of tumor cells. Our studies suggest that UESL exhibits at least a partial smooth muscle phenotype in middle-aged adults, and this specific differentiation may be more common in this age group than in children. Tumor cells of UESL with smooth muscle differentiation in middle-aged adults show phenotypic diversity comparable to those of malignant fibrous histiocytoma with myofibroblastic differentiation.     

Gastrointestinal Stromal Tumor of the Duodenum: A Case Report

The report describes a malignant gastrointestinal stromal tumor occurring in the duodenum in a 71-year-old woman. The neoplasm showed both epithelioid and spindle cell patterns by light microscopy. The ultrastructural features were diagnostic of nerve sheath origin. The tumor had numerous wrapping processes joined by junctions and surrounded by axons. No features of smooth muscle differentiation were identified. Immunocyto-chemistry was inconclusive. The differential diagnosis of such neoplasms is discussed.     

Gastrointestinal Stromal Tumor of the Duodenum: A Case Report

The report describes a malignant gastrointestinal stromal tumor occurring in the duodenum in a 71-year-old woman. The neoplasm showed both epithelioid and spindle cell patterns by light microscopy. The ultrastructural features were diagnostic of nerve sheath origin. The tumor had numerous wrapping processes joined by junctions and surrounded by axons. No features of smooth muscle differentiation were identified. Immunocyto-chemistry was inconclusive. The differential diagnosis of such neoplasms is discussed.