Smooth Muscle Actin Immunoreactivity Research Articles

Challenges in the diagnosis of the enigmatic primary adrenal leiomyosarcoma: two case reports and review of the literature

BackgroundPrimary adrenal leiomyosarcoma is a rare and aggressive mesenchymal tumor derived from the smooth muscle wall of a central adrenal vein or its tributaries; therefore, tumors tend to invade the inferior vena cava and cause thrombosis. The great majority of tumors grow rapidly, which makes the disease difficult to diagnose in its early clinical stages and needs differentiation from adrenocortical carcinomas for the selection of chemotherapy including mitotane which causes adrenal insufficiency.Case presentationWe presented two patients with adrenal leiomyosarcoma who were referred to our hospital with abdominal pain and harboring large adrenal tumors and inferior vena cava thrombosis. The endocrine findings, including serum catecholamine levels, were unremarkable. These two patients were considered clinically inoperable, and CT-guided core needle biopsy was performed to obtain the definitive histopathological diagnosis and determine the modes of therapy. The masses were subsequently diagnosed as primary adrenal leiomyosarcoma based on the histological features and positive immunoreactivity for SMA (smooth muscle actin), desmin, and vimentin.ConclusionsAdrenal leiomyosarcoma derived from the smooth muscle wall of a central adrenal vein or its tributaries is rare but should be considered a differential diagnosis in the case of nonfunctioning adrenal tumors extending directly to the inferior vena cava. CT-guided biopsy is considered useful for histopathological diagnosis and clinical management of patients with inoperable advanced adrenal tumors without any hormone excess.

Biological and Adhesive Properties of an Autologous Protein-Based Fibrin Sealant for Ophthalmological Applications.

The aim of this study was to evaluate the biological and adhesive properties of a new autologous sealant based on plasma rich in growth factors (PRGF), named E-Sealant. Conventional PRGF and a commercial fibrin sealant (Tisseel) were included as controls. The hematological and protein content of E-Sealant was determined. Its bioactivity and biocompatibility were tested for human keratocytes (HKs). To evaluate its adhesion and regenerative capacity, E-Sealant was used on an animal model of conjunctival autograft surgery and compared to Tisseel. E-Sealant presented a high growth factor content with levels similar to those of conventional PRGF. E-Sealant induced proliferative and migratory activity on HK cells equivalent to PRGF. Although autologous membranes induced the proliferation of HKs, cells cultured over Tisseel did not adhere nor proliferate. HK cells showed increased number and flattened morphology over PRGF and E-Sealant compared to scarce and round-shape cells detected in Tisseel. Conjunctival autograft glued with E-Sealant adhered successfully, whereas Tisseel application formed irregular clots. During follow-up, both adhesives showed good integration and no dehiscence. However, Tisseel-treated samples presented slightly increased hemorrhage and inflammation. In contrast to Tisseel, E-Sealant-treated autografts presented a continuous layer of non-keratinized stratified squamous epithelium. Inflammatory infiltrates were minimal in E-Sealant-treated conjunctiva, whereas the Tisseel group showed noticeable immune reactions. Unlike Tisseel-treated grafts, E-Sealant presented low immunoreactivity for smooth muscle actin (SMA), suggesting decreased fibrotic tissue formation. E-Sealant presents optimal biological and adhesive properties suitable for use as an ophthalmic glue, with regenerative purposes superior to commercial fibrin sealants. Our study analyzed the characterization and biological activity of a new autologous fibrin sealant in ocular surface cells and in an animal model in which the adhesive and regenerative properties of the fibrin sealant were evaluated.

Lymphedematous Fibroepithelial Polyp Without Associated Condom Catheter Use: A Case Report With Review of the Literature.

Lymphedematous fibroepithelial polyps are rare proliferations involving the glans penis typically associated with chronic condom catheter usage. To the best of our knowledge, less than 20 cases have been reported in the literature with relatively similar clinical presentation. Herein, we report a case of lymphedematous fibroepithelial polyp not associated with condom usage in a 74-year-old man treated with surgical excision. On histopathological examination, the lesion displayed a hypocellular proliferation of spindled and stellate fibroblasts with intermixed Touton-like giant cells embedded within an edematous stroma with thickened vasculature. Immunohistochemical profiling exhibits strong immunoreactivity for smooth muscle actin, weak positivity for factor XIIIa, and no reactivity for CD34 or desmin. We also conducted a review of the reported range of clinical and histopathological features of this entity in addition to the various hypotheses regarding its pathogenesis. We hope to increase awareness and accurate diagnosis of this entity, which could affect clinical management.

CD56 and smooth muscle actin immunoreactivity in basal cell carcinomas: Are they indicators of differentiation or do they hold a diagnostic use?

Basal cell carcinoma (BCC) is the most common cutaneous malignancy and may show various differentiations. The possible pluripotent stem cell lineage of BCCs, whose origins are controversial today, is thought to be the main reason for the different morphologies. The aim of the study is to evaluate the expression of some neuroendocrine and smooth muscle markers of differentiation in BCCs and investigate the relationship between histopathologic subtypes and recurrence. A total of 128 cases diagnosed as BCC in our center were included. Immunohistochemical studies of CD56, synaptophysin, chromogranin-A, smooth muscle actin (SMA), desmin, caldesmon, and Ki67 were applied. CD56, chromogranin-A, and synaptophysin immunoreactivity were detected in 77.3%, 13.3%, and 0.8% of the cases, respectively. 78.1% showed SMA positivity while no tumor expressed desmin or caldesmon. A correlation between histopathologic recurrence risk groups and CD56 expression was found (p < 0.05). CD56 and SMA immunoreactivity is present in the majority of BCCs. However, the available findings do not support neuroendocrine or smooth muscle differentiation. CD56 antigen can be used for prognostic purposes in detecting high recurrence risk tumors. After the investigation of the expression rates of these two antigens in different cutaneous tumors, it may be appropriate to use them for diagnostic purposes in BCCs.

Immunolocalization of intermediate filaments in the kidney of the dromedary camel (Camelus dromedarius)

Intermediate filaments belong to a large family of proteins which contribute to the formation of the cytoskeleton. The immunolocalization of cytoskeletal proteins has been used extensively in the diagnosis of various renal pathologies. The present study described the immunolocalization of the cytoskeletal proteins vimentin, desmin, smooth muscle actin, and cytokeratin 19 in the normal kidney of the dromedary camel. Kidney samples from eight adult camels were processed for histology and immunohistochemistry. The kidney was enclosed in a renal capsule composed of vimentin immunoreactive fibroblasts and smooth muscle actin immunoreactive smooth muscle cells. The smooth muscle cells in the renal capsule did not exhibit desmin immunoreactivity. Podocytes forming the visceral layer of the glomerular capsule were immunoreactive for vimentin. Immunoreactivity for vimentin and smooth muscle actin in the parietal layer of the glomerular capsule varied, with both reactive and non-reactive cells observed. Intraglomerular mesangial cells were immunoreactive for smooth muscle actin and desmin, but non-reactive to vimentin. The endothelial lining of blood vessels was vimentin immunoreactive, while smooth muscle actin and desmin were demonstrated in the smooth muscle cells of the vessels. The thin limbs of the loops of Henle in cortical nephrons displayed vimentin immunoreactivity. The proximal and distal convoluted tubules, as well as the collecting ducts were negative to vimentin, smooth muscle actin, desmin and cytokeratin 19 immunostaining. In conclusion, the present study has revealed that similarities and differences exist in the immunolocalization of cytoskeletal proteins in the camel when compared to other mammals. The presence of smooth muscle actin in the parietal cells of the glomerular capsule suggests a contractile function of these cells. The results of the study indicate that vimentin and smooth muscle actin can be used as markers for the identification of podocytes and intraglomerular mesangial cells, respectively, in the camel kidney.

Primary pancreatic glomus tumor invading into the superior mesenteric vein: a case report.

BackgroundGlomus tumors are subcutaneous tumors arising from glomus bodies, thermoregulatory components of the skin. These tumors could occur in visceral organs where glomus bodies are not normally present. Herein, we report a case of primary pancreatic glomus tumor with aggressive direct invasion into the superior mesenteric vein (SMV). To the best of our knowledge, this is the second case report of a glomus tumor arising in the pancreas.Case presentationA 46-year-old woman was referred to our hospital due to vomiting with epigastric and back pain. Dynamic-CT revealed a well-circumscribed hypervascular mass, measuring 37 mm in its maximal diameter involving the pancreatic head. Both CT and endoscopic ultrasonography (EUS) revealed direct invasion into the SMV and radiologically suspected tumor thrombus. Biopsy sample obtained by EUS-guided fine needle aspiration revealed proliferation of small cells, round-to-oval tumor cells with round nuclei and scant cytoplasm. A histological diagnosis of pancreatic neuroendocrine tumor, G1 was initially considered. Therefore, subtotal stomach-preserving pancreatoduodenectomy using Child-II reconstruction was subsequently performed. Her SMV was resected and reconstructed due to extensive tumor involvement. Subsequent histopathological analysis revealed solid tumor cells proliferation that comprised oval-shaped nuclei and scant cytoplasm around disorganized or slit-shaped vessels in hematoxylin–eosin-stained slides. Immunohistochemical analysis then demonstrated positive immunoreactivity for smooth muscle actin, vimentin, and CD34, but negative for chromogranin A, synaptophysin, CD56, and signal transducer and activator of transcription 6. Based on these histological findings of resected specimens, the lesion was subsequently diagnosed as a primary pancreatic glomus tumor harboring direct invasion into the SMV. Her postoperative course was uneventful and annual surveys for the following 4 years post-op detected no clinical signs of recurrence.ConclusionsWe report a very rare case of glomus tumor of the pancreas accompanied by venous invasion. Curative surgical resection is the best treatment option for pancreatic glomus tumors. Although pancreatic glomus tumor is rare, it should be taken into consideration in the differential diagnosis of a pancreatic solid tumor with hypervascularity.

Immunohistochemical Characterization of Neurotransmitters in the Episcleral Circulation in Rats.

Episcleral venous pressure (EVP) greatly influences steady-state IOP and recent evidence suggests a neuronal influence on EVP. Yet little is known about the innervation of the episcleral circulation and, more specifically, the neurotransmitters involved. We identify possible neurotransmitter candidates in the episcleral circulation of rats. Eight immersion-fixated rat eyes taken from four animals were cut into serial sections, followed by standard immunohistochemistry. Antibodies against choline acetyltransferase, dopamine-β-hydroxylase, synaptophysine, PGP 9.5, VIP, neuronal nitric oxide synthase (nNOS), substance P, CGRP, and galanin were used. Additionally, colocalization experiments with smooth muscle actin and neurofilament (200 kDa) were performed. In all specimens, the episcleral vessels showed immunoreactivity for smooth muscle actin and were reached by neurofilament (200 kDa)-positive structures. Furthermore, these structures colocalized with immunoreactivity for PGP 9.5, synaptophysine, choline acetyl transferase (ChAT), dopamine-β-hydroxylase, VIP, CGRP, nNOS, substance P and galanin. These findings indicate that there is neuronal input to the episcleral circulation. ChAT and VIP as well as dopamine-β-hydroxylase suggest parasympathetic and sympathetic innervation. Further studies are needed on whether the positively-stained structures are of functional significance for the regulation of the episcleral venous pressure and thereby IOP.

285 - Protein phosphatase 2A (PP2A) inhibition in NAFLD leads to an underlying intestinal fibrotic pathology that is NOX2 dependent

Increased oxidative stress exacerbates the condition of Non-Alcoholic Fatty Liver Disease (NAFLD) which is a global pandemic, leading to its progression to the state of chronic inflammation and fibrosis (NASH). Protein phosphatase 2A (PP2A) is an enzyme that plays an important role in fibrosis, but its role in controlling the production of reactive oxygen species is unclear. Our studies show that the environmental toxin microcystin, an inhibitor of PP2A, specifically inhibits the enzyme and generates higher oxidative stress. The above process activated TGF-β fibrotic signaling pathway in the intestines that was mediated by NOX2. Results using mouse NAFLD models and transformed rat intestinal epithelial cells showed that inhibiting PP2A by administration of microcystin led to increased NOX2 activation, increased SMAD2/3-SMAD4 co-localization and increased alpha smooth muscle actin immuno-reactivity. This process was greatly attenuated in p47 phox knockout mice signifying an important role of NOX2. Mechanistically, rat intestinal epithelial cells were treated with apocynin, DMPO and phenylboronic acid which showed significantly decreased NOX2 activation, SMAD co-localization and α-SMA immuno-reactivity. A significant decrease of NOX2 and TGF-β signaling in NOX4 inhibitor treated samples indicated that there might be a possibility of dependency of NOX isoforms on each other. This study gives us hope to explore novel therapeutic strategies by increasing PP2A in situ by administration of PP2A agonists for the treatment of NASH.

Glomus Tumor of the Kidney: Case report

Abstract Introduction: Glomus tumors are rare benign mesenchymal neoplasms accounting for only 2% of all types of soft tissue tumors. Commonly located in the peripheral soft tissues, they are most frequently encountered in the subungual areas of fingers and toes, and very rarely in visceral organs due to the absence of glomus bodies. To date, 22 cases of primary renal glomus tumors have been described in the literature, of which 17 benign, with no evidence of recurrence or metastasis, three cases of malignant glomus tumor, and two cases with uncertain malignant potential. Case report: We report the 18th case of a benign glomus tumor of the kidney in a 49-year-old female patient, presenting the microscopic appearance (round, uniform cells with indistinct borders, scant finely granular eosinophilic cytoplasm, round nuclei lacking prominent nucleoli, arranged in solid sheets, accompanied by slit-like vascular spaces), the immunohistochemical profile (tumor cells showed immunoreactivity for smooth muscle actin, vimentin, as well as for CD34; they were negative for AE1/AE3, desmin, HMB-45, S-100 protein, renin, and chromogranin), and the differential diagnosis of this rare entity (juxtaglomerular tumor, angiomyolipoma, hemangioma, epithelioid leyomioma, solitary fibrous tumor, carcinoid tumor, and paraganglioma). Conclusion: Primary renal glomus tumors are rare tumors that radiologically can mimic other mesenchymal renal neoplasm. Accurate diagnosis is based on the microscopic appearance and especially the characteristic immunophenotype.

Gastric leiomyosarcoma and diagnostic pitfalls: a case report

BackgroundSince the advent of immunohistochemistry for the diagnosis of stromal tumours, the incidence of leiomyosarcomas has significantly decreased. Nowadays, gastric leiomyosarcoma is an exceptionally rare tumour. We report the second case in the English literature of gastric leiomyosarcoma revealed with massive bleeding and hemodynamic instability and diagnostic pitfalls that we encountered.Case presentationA 63-year-old woman, with 2 years’ history of dizziness and weakness probably related to an anaemic syndrome, presented to the emergency room with hematemesis, melena and hemodynamic instability.On examination, she had conjunctival pallor with reduced general condition, blood pressure of 90/45 mmHg and a pulse between 110 and 120 beats per minute. On digital rectal examination, she had melena. Laboratory blood tests revealed a haemoglobin level at 38 g/L.The patient was admitted to the intensive care department. After initial resuscitation, transfusion and intravenous Omeprazole continuous infusion, her condition was stabilized. She underwent upper gastrointestinal endoscopy showing a tumour of the cardia, protruding in the lumen with mucosal ulceration and clots in the stomach. Biopsies were taken. Histological examination showed interlacing bundles of spindle cells, ill-defined cell borders, elongated hyperchromatic nuclei with marked pleomorphism and paranuclear vacuolization. Immunohistochemistry showed positivity for Vimentine, a strong and diffuse immunoreactivity for smooth muscle actin (SMA). Immunoreactivities for KIT and DOG1 were doubtful.Computed tomography scan revealed a seven-cm tumour of the cardia, without adenopathy or liver metastasis.The patient underwent laparotomy. A total gastrectomy was performed without lymphadenectomy. Post-operative course was uneventful.Histological examination of the tumour specimen found the same features as preoperative biopsies with negative margins. We solicited a second opinion of an expert in a reference centre for sarcomas in France, who confirmed the diagnosis of a high grade gastric leiomyosarcoma.ConclusionGastric leiomyosarcoma is a rare tumour. Diagnosis is based on histological examination with immunohistochemistry, which could be sometimes confusing like in our case. The validation of a pathological expert is recommended.

Histopathological classification and immunohistochemical characterization of canine mammary tumours

The present study was carried out to investigate breed wise and age wise prevalence of canine mammary tumours (CMTs) along with histopathological and immunohistochemical characterization. A total of 97 CMTs samples were collected from different parts of Gujarat, India over period of three years (April 2014-March 2017). The mean age of the dogs, involvement of breeds and mammary glands were recorded. The mean±SD age of all affected dogs was 7.5±2.8 years. Among 12 breeds affected, most cases (n=77) of CMTs were recorded in four breeds viz., Pomeranian, Mongrel, Germen Shepard and Labrador. Caudal abdominal and inguinal mammary glands were frequently showed neoplastic growth. Among histological characterization of 97 CMTs, 16(16.49%) were non neoplastic proliferative/dysplastic lesions, 11 (11.34%) were benign neoplasms and 70 (72.16%) were malignant tumours. Out of 70 malignant neoplasms, epithelial neoplasms, special type epithelial neoplasms, mesenchymal neoplasms and carcinosarcomas were 53(54.64%), 6(6.19%), 8(8.25%), and 3(3.09%), respectively. Further, mixed carcinoma, tubulopapillary carcinoma, solid carcinoma, carcinoma and malignant myoepithelioma, tubular carcinoma and ductal carcinoma were frequently noted. Immunohistochemistry was found to be a powerful tool to classify the CMTs. In the present study, smooth muscle actin (SMA) helped in diagnosing complex adenoma, complex carcinoma, malignant myoepithelioma and fibrosarcoma. In complex adenoma, complex carcinoma and malignant myoepithelioma, myoepithelial cells showed strong SMA immunoreactivity, although stromal myofibroblasts and vascular smooth muscle cells also immunostained.

Primary Omental Leiomyosarcoma: A Rare Case Report

Primary leiomyosarcoma of greater omentum is rare and mimics gastrointestinal stromal tumor (GIST) due to their common origin. A 65 years old male presented with a large mass per abdomen of one year duration. Imaging findings were suggestive of extra-gastrointestinal stromal tumor (E-GIST) arising from greater omentum. The mass was excised. On microscopy, the diagnosis of leiomyosarcoma and E-GIST were considered. The tumor cells showed immunoreactivity for smooth muscle actin, muscle-specific actin, heavy-caldesmon and desmin and were immunonegative for CD117, DOG1 and CD34, hence confirming primary leiomyosarcoma of greater omentum. We present this case for its rarity.

Spindle Cell Atypical Fibroxanthoma: Myofibroblastic Differentiation Represents a Diagnostic Pitfall in This Variant of AFX.

Atypical fibroxanthoma (AFX) is a low-grade, dermal, mesenchymal neoplasm, which lacks a specific lineage of differentiation. The classical histologic appearance of AFX is that of a pleomorphic and spindle cell neoplasm with marked nuclear pleomorphism, mitotic figures, and often prominent storiform pattern that superficially resembles a pleomorphic high-grade sarcoma ("malignant fibrous histiocytoma"). Many histologic variants have been described. We have reviewed 15 cases of AFX characterized by a pure spindle cell morphology that could be easily mistaken for other spindle cell dermal neoplasms. All of our cases were stained with CD68, CD163, CD10, S-100p, p63, wide-spectrum keratin, CD31, CD34, smooth muscle actin (SMA), desmin, calponin, and h-caldesmon. All 15 cases showed an immunoprofile consistent with AFX. In 9 cases, SMA was also strongly expressed; this finding, coupled with the malignant spindle cell histomorphology, can lead to an erroneous diagnosis of cutaneous leiomyosarcoma with potential clinical consequences. Awareness of this pattern of immunoreactivity in this unusual variant of AFX is of importance for avoiding diagnostic misinterpretation. This study intends to characterize the nature and frequency of SMA immunoreactivity in AFX and to discuss the potential diagnostic pitfalls of immunohistochemical markers in distinguishing this entity from other malignant spindle cell neoplasms.

Leiomyoma of the thyroid gland with psammoma bodies.

We report a rare case of leiomyoma of the thyroid gland associated with psammoma bodies. The patient was a 9-year-old black African boy. Prior to this, only five cases of primary thyroid leiomyoma have been reported. Histologically, thyroid leiomyoma was characterised by bundles of spindle smooth muscle cells with blunt-ended nuclei. Psammoma bodies were widely distributed within the tumour. Immunohistochemistry showed positive immunoreactivity for smooth muscle actin, vimentin and desmin, but was negative for a cytokeratin cocktail. Further reports of similar cases is required to ascertain the clinical significance of this lesion.

An Unusual Case of Systemic Inflammatory Myofibroblastic Tumor with Successful Treatment with ALK-Inhibitor.

Systemic inflammatory myofibroblastic tumor is an exceedingly rare entity. A 45-year-old Hispanic female presented with a 6-month history of left-sided thigh pain, low back pain, and generalized weakness. PET/CT scan revealed abnormal activity in the liver, adrenal gland, and pancreas. MRI of the abdomen demonstrated two 6-7 cm masses in the liver. MRI of the lumbar spine demonstrated lesions in the L2 to L4 spinous processes, paraspinal muscles, and subcutaneous tissues, as well as an 8 mm enhancing intradural lesion at T11, all thought to be metastatic disease. A biopsy of the liver showed portal tract expansion by a spindle cell proliferation rich in inflammation. Tumor cells showed immunoreactivity for smooth muscle actin and anaplastic lymphoma kinase 1 (ALK1). Tissue from the L5 vertebra showed a process histologically identical to that seen in the liver. FISH analysis of these lesions demonstrated an ALK (2p23) gene rearrangement. The patient was successfully treated with an ALK-inhibitor, Crizotinib, and is now in complete remission. We present the first reported case, to our knowledge, of inflammatory myofibroblastic tumor with systemic manifestations and ALK translocation. This case is a prime example of how personalized medicine has vastly improved patient care through the use of molecular-targeted therapy.

Renal myopericytoma: A case report with a literature review

Myopericytoma is a rare neoplasm that generally arises from the skin and superficial soft tissues of distal extremities, and is particularly rare in the visceral organs. The current report presents a case of giant myopericytoma showing kidney involvement, which is extremely rare. A 39-year-old male presented to the Department of Urology with a 2-month history of a painless and palpable mass in the region of the left abdomen. Unenhanced computed tomography revealed a 9×10×18-cm3 mass that was heterogeneous with central lower density. The patient underwent radical nephrectomy, including lymphadenectomy, without adjuvant therapy. The tumor was composed of spindle-shaped myoid cells with a concentric arrangement and showed immunoreactivity for smooth muscle actin and cluster of differentiation (CD)10, and had a Ki-67 index of <1%; however, staining was negative for CD34, desmin, S-100 protein, cytokeratin, human melanoma black (HMB)-45, B-cell lymphoma (Bcl)-2 and CD99. Routine follow-up revealed no local or distant metastatic signs of reccurrence for 20 months. The present report shows that renal myopericytoma may be a benign tumor, and surgical excision without adjuvant therapy may be the only potentially curative treatment approach.

Role of Ki-67 as a prognostic factor in gastrointestinal stromal tumors

To investigate primarily the prognostic value of Ki-67, as well as other parameters, in gastrointestinal stromal tumors (GISTs). Ki-67, c-KIT, platelet-derived growth factor receptor-alpha (PDGFRα), smooth muscle actin (SMA), CD34, S100 were stained for immunohistochemistry which was performed on formalin-fixed, paraffin-embeded sections on representative block from each case. Proliferation index counted by Ki-67 antibody was calculated as a number of positive nuclear reaction over 100 cells. Immunoreactivity for c-KIT and PDGFRα was evaluated semiquantitatively (weak, intermediate, strong) and for c-KIT type of reactivity was analyzed (cytoplasmic, membrane and "dot-like" staining). Immunoreactivity for SMA, CD34 and S100 were was evaluated as positive or negative antigen expression. Pathologic parameters investigated in this study included tumor size, cell type (pure spindle, pured epitheloid mixed spindle and epitheloid), mitotic count, hemorrhage, necrosis, mucosal ulceration. Clinical data included age, gender, primary tumor location and spread of disease. χ² test and Student's t-test were used for comparisons of baseline characteristics. The Cox's proportional hazard model was used for univariable and multivariable analyses. Survival rates were calculated by Kaplan-Meier method and statistical significance was determined by the log-rank test. According to the stage of disease, there were 36 patients with localized disease, 29 patients with initially localized disease but with its recurrence in the period of follow up, and finally, 35 patients had metastatic disease from the very beginning of disease. Tumor originated most commonly in the stomach (41%), small intestine was the second most common location (36%). The mean size of primary tumors was 6.5 cm. The mean duration of follow-up was 60 mo. Multiple parameters were analyzed for their effect on overall survival, but no one reached statistical significance (P = 0.06). Analysis of time to progression/relapse in initially localized disease (univariate analysis), tumor size, mitotic count, Ki-67 and type of d-KIT distribution (cytoplasmic vs membrane/"dot-like") showed statistically significant correlation. In multivariate analysis in the group of patients with localized disease, there were only 2 parameters that have impact on relapse, Ki-67 and SMA (P < 0.0001 and P < 0.034, respectively). Furthermore, Ki-67 was analyzed in localized disease vs localized with recurrence and metastatic disease. It was shown that there is a strict difference between these 2 groups of patients (median value was 2.5 for localized disease vs 10.0 for recurrent/metastatic disease, P < 0.0001). It was also shown that the cut-off value which is still statistically significant in terms of relapse on the level of 6%. The curves for survival on that cut-off level are significantly different (P < 0.04, Cox F). Ki-67 presents a significant prognostic factor for GIST recurrence which could be of great importance in evaluating malignant potential of disease.

Carcinosarcoma ex Non-Recurrent Pleomorphic Adenoma Composed of TTF-1 Positive Large Cell Neuroendocrine Carcinoma and Myofibrosarcoma: Apropos a Rare Case

We present a carcinosarcoma ex non-recurrent pleomorphic adenoma composed of a large cell neuroendocrine carcinomatous component and a spindle cell sarcoma with myofibroblastic differentiation. The tumor contained a hyalinized transition zone where the classical PA appeared to acquire two different histopathological patterns of malignant transformation of the epithelial component. The carcinomatous component was strongly and diffusely positive for low-molecular weight cytokeratins (AE1-3), synaptophysin, thyroid transcription factor-1 and focally positive for chromogranin A. All these markers were negative in the sarcomatous component. The sarcomatous component displayed immunoreactivity for smooth muscle actin with a predominantly linear, subplasmalemmal pattern. No expression of CD31, S100 protein, h-caldesmon, desmin, CD34, p63, myogenin, Myo D1 and c-kit was detected. Strong immunohistochemical expression of p53 was documented in both the carcinomatous and sarcomatous components as well as in the atypical epithelial component in the transition zone associated with the hyalinized pleomorphic adenoma.

Intratumoral mast cell number is negatively correlated with tumor size and mitosis in dermatofibrosarcoma protuberans

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumor with intermediate malignancy. The purpose of this study was to evaluate the utility of p53, smooth muscle actin (SMA) and c-kit as immunohistochemical markers and toluidine blue staining for mast cell that can correlate with the clinical outcome and clarify role of mast cells in pathogenesis of tumor. We analysed data for 32 lesions from 31 patients. Fibrosarcomatous type DFSP showed high immunoreactivity for SMA compared with other subtypes (P = 0.026). No differences in p53 immunoreactivity were observed between subtypes. None of tumor cells were immunoreactive with c-kit. The mast cell counts showed a negative correlation with mitosis and tumor size (P < 0.05), implying that mast cells do not have a causative primary role in tumorigenesis but rather play a secondary role.

Fibroblastic rheumatism: A report of 4 cases with potential therapeutic implications

Fibroblastic rheumatism is a rare dermatoarthropathy characterized by the sudden onset of cutaneous nodules, flexion contractures, and polyarthritis. Histopathology in the correct clinical context confirms the diagnosis. Treatment is based on observational data from single case reports. We describe 4 cases, review histologic findings, and discuss therapeutic responses. Cases coded as fibroblastic rheumatism were retrieved from institutional and consultation files. Medical charts and biopsy specimens were reviewed. Elastic stains and immunostains for smooth muscle actin, S100, CD34, desmin, and epithelial membrane antigen were performed on selected cases. Four cases were identified. Patients displayed cutaneous nodules and arthralgias. Flexion contractures/decreased motion were present in two patients; one patient had associated Raynaud phenomenon and erosive joint disease. Biopsy specimens demonstrated a fibroblastic proliferation associated with a collagenous stroma. Growth patterns varied from cellular fascicles to paucicellular randomly arranged spindle cells. Elastic fibers were absent in all cases tested (3/3). Immunohistochemical stains demonstrated immunoreactivity for smooth muscle actin in one of 3 cases in a myofibroblastic pattern. Other stains were negative. One patient had complete resolution of disease with methotrexate. One patient partially responded to interferon-alfa and ribavirin and was subsequently treated with methotrexate with additional improvement. One patient had limited response to all therapies attempted. One patient was lost to follow-up. Small sample size (n= 4) is a limitation. Our data expand the clinical, histologic, and therapeutic response data on fibroblastic rheumatism. Correlation with clinical history is critical to avoid misdiagnosis as other fibrosing lesions. Methotrexate and interferon-alfa are potential therapies.