Journal of Pathology and Translational Medicine

Original Articles

An Immunohistochemical and Polarizing Microscopic Study of the Tumor Microenvironment in Varying Grades of Oral Squamous Cell Carcinoma: Aeman Khalid, Safia Siddiqui, Bharadwaj Bordoloi, Nafis Faizi, Fahad Samadi, Noora Saeed; J Pathol Transl Med. 2018;52(5):314-322. Published online July 27, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.17

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Background
Invasion of epithelial cells into the connective tissue brings about massive morphological and architectural changes in the underlying stroma. Myofibroblasts reorganize the stroma to facilitate the movement of tumor cells leading to metastasis. The aim of this study was to determine the number and pattern of distribution of myofibroblasts and the qualitative and quantitative change that they cause in the collagen present in the stroma in various grades of oral squamous cell carcinoma (OSCC).
Methods
The study was divided into two groups with group I (test group, 65 cases) consisting of 29 cases of well-differentiated squamous cell carcinoma, 25 moderately differentiated SCC, and 11 poorly differentiated SCC, and group II (control group) consisting of 11 cases of normal mucosa. Sections from each sample were stained with anti–α-smooth muscle actin (α-SMA) antibodies, hematoxylin and eosin, and Picrosirius red. Several additional sections from each grade of OSCC were stained with Masson’s trichrome to observe the changes in collagen. For the statistical analysis, Fisher’s exact test, Tukey’s post hoc honest significant difference test, ANOVA, and the chi-square test were used, and p < .05 was considered statistically significant.
Results
As the tumor stage progressed, an increase in the intensity α-SMA expression was seen, and the network pattern dominated in more dedifferentiated carcinomas. The collagen fibers became thin, loosely packed, and haphazardly aligned with progressing cancer. Additionally, the mean area fraction decreased, and the fibers attained a greenish yellow hue and a weak birefringence when observed using polarizing light microscopy.
Conclusions
Myofibroblasts bring about numerous changes in collagen. As cancer progresses, there isincrease in pathological collagen,which enhances the movement of cells within the stroma.

Citations

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Multifractal Alterations in Oral Sub-Epithelial Connective Tissue During Progression of Pre-Cancer and Cancer
Debaleena Nawn, Sawon Pratiher, Subhankar Chattoraj, Debjani Chakraborty, Mousumi Pal, Ranjan Rashmi Paul, Srimonti Dutta, Jyotirmoy Chatterjee
IEEE Journal of Biomedical and Health Informatics.2021; 25(1): 152. CrossRef

Endobronchial Smooth Muscle Tumors: A Series of Five Cases Highlighting Pitfalls in Diagnosis: Tripti Nakra, Aanchal Kakkar, Shipra Agarwal, Karan Madan, Suresh C Sharma, Deepali Jain; J Pathol Transl Med. 2018;52(4):219-225. Published online July 11, 2018; DOI: https://doi.org/10.4132/jptm.2018.05.16

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Abstract PDF

Background
Primary endobronchial smooth muscle tumors (SMTs), which are extremely rare, include endobronchial leiomyomas and leiomyosarcomas. Clinically, SMTs present with signs and symptoms of bronchial obstruction, and lack specific radiological findings. Thus, histopathological examination is required for accurate diagnosis as well as for tumor grading. We examined the histomorphological and immunohistochemical features of endobronchial SMTs and highlighted pitfalls in diagnosis, particularly when using small biopsies.
Methods
Cases of primary endobronchial SMTs diagnosed at our Institute over the last 6 years (2012–2017) were retrieved from the departmental archives. Histopathological features and immunohistochemistry performed for establishing the diagnosis were reviewed.
Results
Five cases of SMTs occurring in endobronchial locations were identified. These included three cases of leiomyoma, and two cases of leiomyosarcoma. The age distribution of patients ranged from 13 to 65 years. Leiomyomas showed more consistent staining with smooth muscle markers (smooth muscle actin, desmin, and smooth muscle myosin heavy chain), while tumors of higher grade showed variable, focal staining, leading to erroneous diagnosis, especially on small biopsies.
Conclusions
The diagnosis of endobronchial SMTs relies on histopathological examination, for both confirmation of smooth muscle lineage and determination of the malignant potential of the lesion. Appropriate immunohistochemical panels including more than one marker of smooth muscle differentiation are extremely valuable for differential diagnosis from morphological mimics, which is necessary for instituting appropriate management.

Citations

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Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
Yinfeng Wang, Yixiang Zhang, Ruirui Tong
Open Life Sciences.2024;[Epub] CrossRef
Pediatric endobronchial tumors with a mimicker: A case series
Kulwiwat Promsawasdi, Teerasak Phewplung
Pediatric Pulmonology.2024; 59(10): 2669. CrossRef
Smooth Muscle Conditions of the Chest
Matthew R. McCann, Lucas R. Massoth, Carlos A. Rojas, Yin P. Hung, John P. Lichtenberger, Gerald F. Abbott, Justin T. Stowell
Journal of Thoracic Imaging.2021; 36(5): 263. CrossRef
A Well-Defined Endobronchial Tumor in a 26-Year-Old Man
Christina Triantafyllidou, Petros Effraimidis, Mirjam Schimanke, Simone Ignatova, Anders Ringman, Susann Skoog, Farkas Vánky, Miklós Boros, Karin Cederquist
Chest.2021; 159(5): e313. CrossRef
Primary Pulmonary Leiomyoma
Mohammad Abu-Hishmeh, Gowthami Kobbari, Fouzia Shakil, Oleg Epelbaum
Journal of Bronchology & Interventional Pulmonology.2020; 27(4): e54. CrossRef

Case Report

Smooth Muscle Hyperplasia of the Epididymis: Report of A Case and Review of the Literature.: Hyun Soo Kim, Ji Youn Sung, Gou Young Kim, Sung Jig Lim, Hyun Cheol Kim, Hyung Lae Lee; Korean J Pathol. 2009;43(2):177-181.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.177

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Abstract PDF

A 66-year-old man underwent surgery to remove an incidentally discovered non-tender intrascrotal mass. Ultrasonography revealed an irregular-margined, heterogeneous mass-like lesion in the epididymal tail. The mass was relatively well circumscribed but unencapsulated, irregular and firm; it consisted of expansile, increased smooth muscle fascicles originating from the epididymal muscular coat. Its cellular growth pattern lacked the cohesive, well-circumscribed proliferation pattern typical of a leiomyoma. A diagnosis of smooth muscle hyperplasia of the epididymis was made. Although ultrasonography is the imaging modality of choice for evaluating suspected intrascrotal masses, there are times when it cannot reliably identify the character of the masses and distinguish malignant from benign lesions. Ill-defined, solid extratesticular masses, that are ultrasonographically ambiguous, should be excised and confirmed histopathologically and smooth muscle hyperplasia of the epididymis should be included in the differential diagnosis of solid extratesticular masses.

Citations

Citations to this article as recorded by

Smooth muscle hyperplasia of the testicular adnexa: a clinicopathologic study of 12 cases
Fatimah Alruwaii, David J. Grignon, Muhammad T. Idrees
Human Pathology.2020; 99: 27. CrossRef
Hiperplasia muscular paratesticular (epididimaria) pseudotumoral. Descripción de 2 casos
Inmaculada Ruiz Molina, Vicente Cívico Amat, Beatriz Santiago Agredano
Medicina Clínica.2019; 152(5): e25. CrossRef
Pseudotumoral paratesticular (epididymal) muscle hyperplasia. Two case reports
InmaculadaRuiz Ruiz Molina, Vicente Cívico Amat, Beatriz Santiago Agredano
Medicina Clínica (English Edition).2019; 152(5): e25. CrossRef
Smooth muscle hyperplasia of the epididymis
O Blach, AM Pollock, D Douglas
Journal of Surgical Case Reports.2011; 2011(10): 10. CrossRef

Original Articles

The Expression of Transforming Growth Factor-beta1 and alpha-Smooth Muscle Actin is Increased in the Human Myxomatous Valve.: Jeong Hwan Park, Ho Joong Youn, Jung Sook Yoon, Chul Soo Park, Soo Sung Oh, Woo Baek Chung, Jong Won Chung, Yun Seok Choi, Dong Hyun Lee, Yong Seog Oh, Wook Sung Chung, Soon Jo Hong, Youn Soo Lee, Sung Bo Sim, Sun Hee Lee; Korean J Pathol. 2009;43(2):152-156.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.2.152

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Abstract PDF

BACKGROUND
In vitro experimental studies have reported that transforming growth factor-beta1 (TGF-beta1) stimulates the production of alpha-smooth muscle actin (alpha-SMA) in porcine valves. However, the relation between TGF-beta1 and alpha-SMA in myxomatous valves has not been elucidated.
METHODS
We classified 27 subjects into two groups: 1) myxomatous group (M:F=11:12, mean age=55+/-15 years) and 2) rheumatic group (M:F=3:1, mean age=41+/-17 years) according to preoperative echocardiographic and postoperative histologic findings. Twenty-seven valve specimens from the patients who underwent valve replacement were obtained. Tissue samples were analyzed by immunohistochemistry for TGF-beta1 and alpha-SMA. The positively stained areas were measured using an image analysis program (Image Pro-Plus 4.5), and then the TGF-beta1 volume fraction (TGF-VF) and alpha-SMA volume fraction (alpha-SMA-VF) were calculated.
RESULTS
TGF-VF in myxomatous valves was higher than in rheumatic valves (2,759+/-2,294 vs 864+/-276, p=0.04). alpha-SMA-VF in myxomatous valves was higher than in rheumatic valves (4,122+/-2,275 vs 2,421+/-844, p=0.002). There was a significant correlation between TGF-beta1 and alpha-SMA in myxomatous valves (r=0.38, p=0.04). There was no significant correlation between TGF-beta1 and alpha-SMA in rheumatic valves (r=-0.50, p=0.67).
CONCLUSIONS
TGF-beta1 and alpha-SMA may be related to the pathogenesis of myxomatous valves. The activation of TGF-beta1 might increase the expression of alpha-SMA in human myxomatous valves.

Citations

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Apoptosis and abundance of Bcl-2 family and transforming growth factor β1 signaling proteins in canine myxomatous mitral valves
Sirilak Surachetpong, Treenate Jiranantasak, Anudep Rungsipipat, E. Christopher Orton
Journal of Veterinary Cardiology.2013; 15(3): 171. CrossRef
Pathology, protein expression and signaling in myxomatous mitral valve degeneration: Comparison of dogs and humans
Heike Aupperle, Sirilak Disatian
Journal of Veterinary Cardiology.2012; 14(1): 59. CrossRef

Expression of CD44 Splice Variants(v4/5 and v6), alpha-Smooth Muscle Actin, and nm23 Proteins in IB-IIB Uterine Cervical Cancer.: Hee Kyung Chang, Man Ha Huh, Dong Hee Kim, Un Dong Park; Korean J Pathol. 1997;31(6):546-556.

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Abstract PDF: We examined the expressions of CD44 splice variants (v4/5, v6), alpha-smooth muscle actin, nm23 to evaluate their roles as prognostic factors in 70 cases of uterine cervical carcinoma (stage IB to IIB) who were surgically treated from January 1989 to June 1990 with a clinical follow-up of a minimum of 5 years. The expression was examined by an immunohistochemical method using archival formalin fixed paraffin embedded tissue. In the 70 cases, 61 cases were squamous cell carcinoma and 9 cases were adenocarcinoma. CD44v4/5, CD44v6, alpha-smooth muscle actin, and nm23 were detected in 41.4%, 70%, 100%, and 74.3% of tumor samples, respectively. CD44 splice variants and nm23 showed membrane and cytoplasmic staining of tumor cells, respectively. The expression of alpha-smooth muscle actin showed cytoplasmic staining confined to stromal cells and was classified into three grades by the extent in stromal cells: with less than 10% of stromal cells; 32.9%, 10-50% of stromal cells; 40.0%, more than 50%; 27.1%. These expressions were not correlated with histologic types, lymph node involvement, recurrence, and grades of tumor infiltrating lymphocyte (TIL). But CD44v4/5 had significantly inverse correlation with TIL (p=0.049). The expression of CD44v4/5 was significantly correlated with that of CD44v6 (p=0.05), and that of alpha-smooth muscle actin was inversely correlated with that of nm23 (p=0.049). In conclusion, in FIGO IB-IIB uterine cervical carcinoma CD44 variants, nm23, and SMA show high prevalence, however, with little prognostic significance assessed by recurrence and lymph node metastasis.

Expression of Alpha Smooth Muscle Actin and Lysozyme in Various Glomerular Diseases.: Sun Hee Sung, Woon Sup Han; Korean J Pathol. 1998;32(1):51-57.

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Abstract PDF: The cells of glomerular mesangium is composed mostly of intrinsic contractile mesangial cells and a few macrophages. Injury to the mesangium is central to many glomerular diseases. This study was aimed to evaluate and compare the expressions of alpha-smooth muscle actin (ASMA) and lysozyme in the mesangium of various human glomerular diseases and also of according to the severity of their progressions. We performed immunohistochemical and transmission electromicroscopic examinations in 51 cases of renal biopsy including 5 normal kidneys. The results were as follows; (1) ASMA staining was negligible in normal glomeruli. (2) Increased ASMA staining was observed in the mesangium of glomeruli from all specimens of primary glomerular disease, regardless of their diagnosis. (3) The staining intensity of ASMA in mesangium was mild in minimal change disease and membranous glomerulonephritis, and strong in focal segmental glomerulosclerosis (FSGS), diffuse mesangial hypercellularity, membranoproliferative glomerulonephritis (MPGN), and IgA nephropathy (IgAN). (4) The staining intensity of ASMA have no correlation with mesangial immune deposits. (5) The staining intensity of ASMA in mesangium was inversely correlated with the disease progression in FSGS and IgAN. (6) Glomeruli showing global or segmental sclerosis invariably lacked ASMA. (7) Compared with ASMA, the mesangial cells with lysozyme expression were very rare, even though it was in proportion to ASMA staining. Interstitial ASMA expression was confined to fibrotic area in various glomerular diseases. In conclusion, the expression of ASMA and lysozyme in mesangium are increased in a variety of glomerular diseases, regardless of disease entity. Their intensity was in proportion to the mesangial cell proliferation. In progressive glomerulonephritis, such as IgAN and FSGS, the increased expression of ASMA was prominent in the early lesion, and decreased with the progression of the glomerular sclerosis.

Expression of Glomerular-Smooth Muscle Actin and Vimentin in Idiopathic Membranous Nephropathy as Prognostic Indicators.: Min Jin Lee, Ok Kyung Kim; Korean J Pathol. 2001;35(1):26-34.

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Abstract PDF: BACKGROUND
The natural history of idiopathic membranous nephropathy (IMN) is heterogeneous with some patients showing spontaneous remission while others show a progressive course leading to end-stage renal failure. We tried to assess quantitatively alpha-smooth muscle actin (alpha-SMA) and vimentin expression as markers to predict the outcome of membranous nephropathy.
METHODS
This study included 24 patients with biopsy proven IMN. We measured the volume of the positive area for alpha-SMA and vimentin within the glomeruli and compared the results with 5 patients in the normal control group. We evaluated glomerular alpha-SMA and vimentin expression in correlation with BUN and serum creatinine level at the time of diagnosis and after treatment.
RESULTS
Glomerular alpha-SMA and vimentin in IMN were higher than in the control group. Glomerular alpha-SMA was significantly higher in progressive IMN than in non-progressive IMN. The glomerular alpha-SMA was sifnificantly correlated with BUN and serum creatinine at last follow-up (p<0.05), but there was no statistically significant correlation at diagnosis. The glomerular vimentin was not different between progressive and non-progressive groups.
CONCLUSION
These data suggest that the expression of glomerular alpha-SMA may be a useful prognostic indicator and may be able to differentiate between patients with membranous nephropathy who respond well to treatment and those who continue to progress.

Expressions and Diagnostic Usefulness of MIB-1 and p53 in Uterine Smooth Muscle Tumors.: Mi Jin Kim, Yong Jin Kim, Seung Ho LeeSeungHo; Korean J Pathol. 2001;35(6):524-530.

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Abstract: BACKGROUND
Controversy still remains concerning the criteria for the categorization of uterine smooth muscle tumors by conventional histologic examination. Various ancillary techniques have been used to improve diagnostic accuracy.
METHODS
Immunohistochemical study of MIB-1 and p53 was performed on 10 usual leiomyomas (UL), 13 cellular leiomyomas (CL), 5 bizarre leiomyomas (BL), 2 cases of intravenous leiomyomatosis (IL), 5 smooth muscle tumors of uncertain malignant potential (STUMP) and 8 leiomyosarcomas (LMS), to investigate the diagnostic value of MIB-1 and p53 in uterine smooth muscle tumors.
RESULTS
The MIB-1 labelling index was low in ULs and their variants (mean 5.67+/-5.53), but it was increased in STUMPs (17.67+/-6.51) and markedly increased in LMSs (35.71+/-11.35). In ULs and their variants, no immunostaining for p53 was noted except in one case of BL, while 2 (40%) of 5 STUMPs and 3 (38%) of 8 LMSs showed positive reactions for p53. There were significant differences among leiomyoma, STUMP and LMS in the MIB-1 labelling index and p53 expression.
CONCLUSIONS
These results suggest that both abnormal expressions of p53 and a high MIB-1 labelling index are frequently associated with leiomyosarcoma. Our data also indicate that the classification system of Kempson and Hendrickson is well correlated with the MIB-1 labelling index.

Differential Expression of CD34 and Smooth Muscle Actin in the Stroma of Small Lung Adenocarcinoma with Mixed Bronchioloalveolar and Invasive Components.: Mee Sook Roh, Jong Woo Choi, Hyoun Wook Lee, Hyuk Chan Kwon, Tae Ho Park, Phil Jo Choi, Chang Hun Lee, Bong Kwon Cheon; Korean J Pathol. 2005;39(3):158-163.

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Abstract PDF: BACKGROUND
Absence of CD34-positive fibroblasts was reported within the stroma associated with invasive carcinomas. Conversely, tumor-associated desmoplastic stroma is characterized by the presence of smooth muscle actin (SMA)-reactive myofibroblasts. The present study was undertaken in order to elucidate whether the different distributions of stromal CD34-positive fibroblasts and SMA-reactive myofibroblasts are sensitive or specific markers of tumor invasion in small lung adenocarcinomas.
METHODS
Immunohistochemical stainings for CD34 and SMA were done in 37 peripheral adenocarcinomas less than 3.0 cm in diameter, including 16 adenocarcinomas with bronchioloalveolar carcinoma (BAC) and invasive components (mixed), and 21 invasive adenocarcinomas without BAC components (invasive).
RESULTS
The fibroblasts within the BAC components of the mixed group were mainly CD34-positive (81.2%) and preferentially SMA-negative (56.3%). In contrast, the fibroblasts within the invasive components of the mixed group were mainly CD34-negative (75.0%) and SMApositive (87.5%). The stromal cells of the invasive group were mostly negative for CD34 (90.5%) and positive for SMA (95.3%).
CONCLUSIONS
The loss of CD34 and the acquisition of SMA in the stromal cells within the tumor were related to tumor invasion (p<0.05). Thus, expression patterns of CD34 and SMA can be used to detect small foci of early stromal invasion in adenocarcinomas of the lung.

Distribution of Smooth Muscles in Hemorrhoids.: Jae Gul Chung, Ghee Young Choe, Gyung Yub Gong, Eun Sil Yu, Jin Cheon Kim, In Chul Lee; Korean J Pathol. 1994;28(2):154-159.

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Abstract PDF: Hemorrhoids are one of the commonest disorders specific to the human. However, the pathogenesis is not well understood so far. Anal submucosa is largely composed of blood vessels, loose connective tissue and smooth muscles, forming muscular network around the venous plexuses. We analyzed the distribution of smooth muscles in the hemorrhoidal tissues. Immunohistochemical stainings for desmin, vimentin, and Factor VIII related antigen were performed using six freshly frozen hemorrhoidal tissues. All of them were diagnosed as external hemorrhoids. Four anal tissues from Miles' operation specimen without hemorrhoids were used as normal controls. In all six cases, venous plexuses were variably dilated and smooth muscle cells were unevenly distributed. In minimally involved areas, there were relatively sufficient amount of perivascular smooth muscles which were arranged in their bundles. In contrast, only single scattered cells or very small amount of smooth muscle bundles were noted around the dilated vascular plexuses in severely affected areas. In two severe hemorrhoidal tissue samples, vascular plexuses were markedly dilated and only single scattered smooth muscle cells were seen. In conclusion, the total amount of smooth muscles in the submucosa of hemorrhoid tissue was reduced than those of the normal controls. The degree of hemorrhoidal dilation was inversely related to the amount of smooth muscles. However, causal relation between diminution of submucosal smooth muscles and venous dilation remains to be clarified.

Smooth Muscle Tumors of the Stomach : A clinicopathologic analysis of 46 cases.: Mee Soo Chagn, Yong Il Kim, Woo Ho Kim; Korean J Pathol. 1991;25(5):418-426.

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Abstract: This study was undertaken to characterize the clinicopathologic features of smooth muscle tumors of the stomach with additional regard to recent controversy over the gastrointestinal smooth mscle tumors. A total of 46 consecutive cases(47 tumors) of surgically resected or excised gastric smooth muscle tumors, were assessed for review. The criteria for malignancy applied in this study were one of the followings; (1) 5 or more mitoses/10 HPF or (2) 1-4 mitoses/10 HPF with tumor cell necrosis and 5 cm or greater in tumor size. The tumors were classified as ordinary leiomyoma in 24 cases(25 tumors), epithelioid leiomyoma in 3, cellular leiomyoma in 6, ordinary leiomyosarcoma in 10, myxoid leiomyosarcoma in 2, and epithelioid leiomyosarcoma in 1. Of the 46 cases, 13 cases(28%) were categorized as malignant smooth muscle tumor. But immunohistochemical study for S-100 protein, desmin and vimentin(5 cases), and ultrastructural study(2 cases) support that myogenic or neurogenic differentiation is evident simultaneously within the same tumor, regardless of malignancy, and that even the differentiated tumor cells seem to express such direction toward immature smooth muscle cell or nerve cell.

Immunohistochemical Study of Gastrointestinal Stromal Tumors.: Jung Weon Shim, Hye Jae Cho, Ill Hyang Ko, Ok Kyung Kim; Korean J Pathol. 1991;25(2):93-103.

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Abstract PDF: Historically, gastrointestinal stroma tumors (GIST) have been considered as smooth muscle tumors, but the controversy over this histogenesis is provoked due to various results with utilizing immunohistochemical methods. In andeffort to further clarify the histogenesis of GIST, we performed the immunohistochemical study, as well as histopathologic reexamination, of 24 cases, all diagnosed as smooth muscle tumors of gastrointestinal tract, from Seoul Paik Hospital and Ewha University Hospital between 1980 and 1989, and the main results were as follows; 1) In the histopathologic features by light microscopic study, 11 benign and 13 malignant lesions (including one high grade malignancy and 12 low-grade malignant lesions) were disclosed. 2) In the immunohistochemical study, all tumors showed Vimentin positivity (100%), but no tumor showed S-100 protein positivity (0%), and 7 cases (29.1%) showed Desmin positivity. Positive reaction for Desmin made it possible to suggest that the histogenesis of GIST be in smooth muscle, and neurogenic origin would be excluded by all negativity for S-100 protein. In summary, we would like to conclude that GIST would be smooth muscle tumors on account of their morphological characteristics and their intramural location, but most of them appear poorly differentiated by immunohistochemical method.

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