Ultrastructural differences between synovial sarcoma and solitary fibrous tumor: comparative study in adult patients from the National Cancer Institute of Mexico.

Synovial sarcoma (SS) and solitary fibrous tumor (SFT) are entities with considerable morphological and immunohistochemical similarities that sometimes show a non-confirmatory profile (TLE1 negative, CD34 and focal or negative STAT6 and lack of specific fusion IHC markers), in which the utility ultrastructure is unknown. A cross-sectional, retrospective, analytical, nonexperimental study was carried out by the Department of Pathology of the National Cancer Institute of Mexico (INCan) e from January 1, 2009 to December 31, 2018. With 17 SFT cases with diffuse or focal CD34 and STAT6 positivity and 18 cases of SS with positive FISH molecular test t(X:18) breakapart were studied by electron microscopy of fresh glutaraldehyde fixed or paraffin-embedded tissue. The ultrastructural findings with a significant difference present in the SS were tandem tight junctions, desmosomes and abundance of dilated rough endoplasmic reticulum (RER) cisternae (p < 0.001, 0.003, and 0.001, respectively); while in the (SFT) the presence of abundant glycogen, basal lamina, long and slender cytoplasmic processes, pinocytic vesicles, hemidesmosomes, and/or dense plaques, collagen skein, and microvilli-like buds (p = 0.028, 0.005, and <0.001 for the last five). We then infer that the five distinctive markers of the SFT are the collagen skeins intermingled with cellular processes in a shape of "squid can," and the pinocytic vesicles as they were not observed in any case of SS. Conversely, tandem junctions were not found in any SFT case. Although the presence of multivesicular buds in the SFT was not significant, it had not been previously described.

Myxoinflammatory fibroblastic sarcoma: ultrastructural study of 7 cases.

Since first described, several studies about Myxoinflammatory fibroblastic sarcomas (MIFS) have been published stating the clinicopathological, morphological and immunohistochemical features. However, the ultrastructural findings of these MIFS are limited. Thus, the objective of the present paper is to describe the ultrastructural characteristics of these type of tumors by utilizing tissue that was embedded in paraffin and submitted for immunohistochemistry.The tissue of seven different cases was obtained for ultrastructural study with automatized staining devices, that were later observed by using transmission electron microscopy. Histologically all cases displayed conventional structures of Myxoinflammatory fibroblastic sarcoma (Reed-Sternberg like cells, pseudolipoblasts and emperipolesis). Conversely, two of them exhibited high-grade components, one rich in osteoclastic type giant cells and hypercellular areas, and another one rich in inflammation (Hodgkin-like).After immunohistochemistry, all the samples revealed positivity for CD68 with six cases CD163 and five being positive to CD34, Cyclin-D1, and D2-40. Ultrastructural findings indicated rough endoplasmic reticulum with dilatation of the cisterns that indented the nuclei ("soccer ball" cells), abundant lysosomes, phagolysosomes, and intermediate filaments evidencing this entity as a morphologic continuum that exhibited modified fibroblastic phenotype and variable proportion of macrophagic differentiation.

Synovial sarcoma with ossification and calcification with SS18 immunochemical expression and rearrangement by fluorescent in situ hybridization.

Synovial sarcoma is a soft tissue tumor of uncertain origin. Generally, it is a monophasic spindle cell neoplasm that can have glandular-like structures. Ossification and presence of calcification is a rare phenomenon with only a few reported cases. We present the case of a young male with a synovial sarcoma of the right foot. Histology revealed prominent deposits of tumoral osteoid and coarse calcifications. The diagnosis was confirmed by the expression of SS18 by immunohistochemistry and the demonstration of the rearrangement of the SS18 gene by fluorescent in situ hybridization. We reviewed the literature for synovial sarcoma with prominent ossification or calcification, and to the best of our knowledge, this is the first case with expression of SS18 by immunohistochemistry. The main differential diagnoses are osteosarcoma (both primary of bone and extraosseous) and sclerosing epithelioid fibrosarcoma.

Clinicopathological and immunohistochemical behavior of ductal carcinoma of the salivary and lacrimal gland in a Mexican Mestizo population.

PURPOSE: Salivary gland tumors are rare and include benign and malignant entities with different behavior and prognosis. Salivary gland carcinoma accounts for 0.2% of all cancers and 5-9% of head and neck carcinomas. We aim to describe the clinicopathological characteristics and discuss the immunohistochemical findings of salivary ductal carcinoma. METHODS: We obtained 17 cases (2.3%) of salivary ductal carcinoma (SDC) from 727 patients with parotid tumors at our cancer center from a database covering a 22-year period (1996-2018). Two pathologists confirmed the diagnosis and excluded 6 cases. Eleven cases were assessed by immunohistochemistry (IHC) for HER2, estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), mammaglobin, P53, GATA3, S100, cytokeratins (7,8,14,18, and 20), P63, PAX8, calponin, and SOX10. RESULTS: Eleven SDC cases were in advanced stage, and 80% had metastasis. All cases were surgically treated, and 40% received different adjuvant chemotherapy regimens. we found that most patients were dead of disease. The histological and immunohistochemical analysis showed that 70% of cases were high-grade, 40% were positive for HER2, and 50% for AR. Moreover, a high Ki-67 proliferative index was detected in all cases. We observed luminal differentiation in 50% of cases. CONCLUSION: SDC is a rare entity and survival is very poor. It is histologically similar to ductal carcinoma of the breast. However, important differences exist that help to distinguish them in case of synchronous cancers. The clinical behavior of SDC seems to be more aggressive and IHC analysis is useful for designing therapies.

Myofibroblastic lesions in the oral cavity: Immunohistochemical and ultrastructural analysis.

OBJECTIVE: To immunohistochemically characterize a group of oral myofibroblastic lesions (MLs) and to evaluate the ultrastructural features of myofibroblasts. MATERIAL AND METHODS: Using a tissue microarray technique (TMA), cases of myofibroma (MF), of nodular fasciitis (NF), of desmoplastic fibroma (DF), and of myofibroblastic sarcoma (MS) from the Universidad Autónoma Metropolitana Xochimilco, and a Private Oral Pathology Service in Mexico City were stained with antibodies against alpha-smooth muscle actin (α-SMA), H-caldesmon, vimentin, desmin, ß-catenin, CD34, anaplastic lymphoma protein kinase (ALK-1), and Ki-67. RESULTS: Nineteen of the 22 MF cases, 2/5 of the NF cases, 1/10 of the DF cases, and 1/2 of the MS cases were positive for α-SMA. 1/2 of the MS cases were positive for desmin; 6/10 of the DF cases were positive for ß-catenin, and 2 of the MF cases were positive for ALK-1. All of the MLs were positive for vimentin and negative for H-caldesmon and CD-34. The Ki-67 labeling index in all of the 8/22 MF, 3/5 NF, and 2/2 MS cases was ≥10%. For all of the MLs evaluated, ultrastructural analysis revealed spindle-shaped cells containing endoplasmic reticulum and peripheral actin filament bundles. CONCLUSION: In certain myofibroblastic lesions, the use of auxiliary techniques (such as immunohistochemistry) can be critical for differential diagnosis.

Giant-cell ependymoma: Presentation of a case of the sacral region and literature review.

Ependymoma is a rare central nervous system neoplasm with an even rarer morphologic variant called giant-cell ependymoma (GCE). GCE has a characteristic discrepant, malignant-like morphology but indolent behavior. We present the case of a 21-year-old female with an extra-axial GCE located in the sacral region. To date, 16 cases of sacral GCE have been reported in the literature, with 4 cases in the sacral region; however, all those cases were intra-axial. We present the first case of an extra-axial sacral GCE.

Oligodendroglial cell proliferation arising in an ovarian mature cystic teratoma. Clinicopathological, inmunohistochemical, and ultrastructural study of a case that may represent an oligodendroglioma.

Ovarian mature cystic teratoma (OMCT) is an ovarian benign neoplasm with excellent prognosis presenting components of the three germinal layers. However, transformation into a malignant neoplasm is a rare event (so-called somatic transformation). In most of the cases, the malignant component expresses as epidermoid carcinoma, but occasionally central nervous system tumors occur. Some of the previously reported tumors are astrocytoma, glioblastoma, and ependymoma. Somatic transformation of OMCT into an oligodendroglioma is exceptional. We report a 19-year-old female with a left OMCT with an area of oligonedroglial cells proliferation characterized by immunohistochemical studies with positivity for GFAP and S100, with a low Ki67 index (5%). Additionally, electron microscopy revealed oligodendrocytes with parallel bundles of cytoplasmic intermediate filaments, confirming the oligodendroglial nature of the proliferation. The patient was treated only with left oophorectomy, and three and half years after surgery, there is no evidence of disease.

Diagnostic efficacy of electron microscopy and pleural effusion cytology for the distinction of pleural mesothelioma and lung adenocarcinoma.

The diagnosis of malignant pleural mesothelioma (MPM) is challenging and requires immunohistochemistry or electron microscopy assays to specifically differentiate MPM from lung adenocarcinoma. An ultrastructural study of fresh tissue is considered to be the "gold standard." In most cases, the first diagnostic approach is performed on pleural effusion, and in some patients, this is the only available sample for diagnosis. The aim of the present study is to evaluate if an examination of pleural effusion samples based on electron microscopy (EMpe) is a useful tool for the differential diagnosis of MPM and lung adenocarcinoma. An EMpe study was performed in 25 pleural effusion samples. Histological and immunohistochemical markers confirmed the diagnosis of either mesothelioma (5) or adenocarcinoma (20). Of the five cases that were diagnosed with mesothelioma, two samples (40%) showed cells with "bushy" microvilli, which are characteristic of mesothelioma, by EMpe, and three were acellular (60%). Of the 20 cases of adenocarcinoma, EMpe showed cells with short microvilli in 9 (45%), and 11 were acellular (55%). EMpe identifies unequivocal morphological changes that are useful for the differential diagnosis of MPM or adenocarcinoma when the pleural effusion sample contains evaluable tumor cells.

Utility of CD99 Paranuclear Expression in the Differential Diagnosis of Merkel Cell Carcinoma.

BACKGROUND: Recent reviews have referred to the paranuclear dot-like staining pattern of CD99 in several neoplasms, including solid pseudopapillary tumors in the pancreas, colonic adenocarcinomas, and colonic adenomas as well as in Merkel cell carcinoma (MCC). The aim of this work was to explore the utility of CD99 paranuclear staining in the differential diagnosis of MCC. MATERIAL AND METHODS: We explore paranuclear dot-like CD99 expression in several small, round blue cell neoplasms, including neuroendocrine neoplasms, Ewing sarcomas/primitive neuroectodermal tumors (EWS/PNET), melanomas, small cell lung carcinomas (SCC), lymphoblastic lymphoma/leukemia, and rhabdomyosarcomas, in comparison with 33 cases of MCC, to determine the specificity of the paranuclear dot-like CD99 expression in MCC. RESULTS: Twenty MCC (60%) demonstrated focal expression of CD99 and of those, 14 (42.4%) showed the characteristic paranuclear dot-like expression. CD99 was also paranuclear positive in 4 of 11 (36%) SCC, in 3 of 7 (43%) EWS/PNET, in 1 of 6 (16%) lymphoblastic lymphoma/leukemia cases, in 3 of 3 (100%) rhabdomyosarcomas and all melanomas were negative for the CD99 reaction. CONCLUSION: CD99 paranuclear dot-like expression was not exclusive of the MCC compared with several neoplasms included in its differential diagnosis. This expression is not a great diagnostic aid.

Immunolocalization of VEGF-A and orosomucoid-1 in odontogenic myxoma.

OBJECTIVE: The aim of the present study was to determine and establish the immunohistochemical distribution of VEGF-A and ORM-1 protein in odontogenic myxomas to suggest a possible function in the biological behavior of odontogenic myxomas. MATERIALS AND METHODS: A total of 33 odontogenic myxoma cases and three tooth germs were included. Immunohistochemistry was performed to localize VEGF-A and ORM-1 proteins in tumor cells, endothelial cells and extracellular matrix in the odontogenic myxomas. The intratumoral microvessel density (MVD) was determined with CD34 and Factor VIII antibodies. RESULTS: Immunopositivity was strong in the endothelial cells, which compose various vessels, and in the randomly oriented stellate, spindle-shaped and round tumoral cells with long cytoplasmic processes. More than half of the extracellular matrix lacked expression of VEGF-A. ORM-1 expression was strong in both endothelial cells and tumor cells, and the myxoid extracellular matrix was positive, with moderate or strong immunoexpression in all cases. An important finding of this study was the statistically significant positive correlation between the expression of ORM-1 and VEGF-A in tumor cells (p=0.02). CONCLUSIONS: The results of this study suggest that the expression of VEGF-A and ORM-1 may be associated with two mechanisms (angiogenesis and tumor structural viscosity) that may influence tumor growth in odontogenic myxoma.

Mammary analogue secretory carcinoma (MASC) of salivary gland in four Mexican patients.

The Clinco-pathological, immunohistochemical and molecular findings of four cases of Mammary Analogue Secretory Carcinoma (MASC) of salivary glands found in Mexico are described. The cases were extracted from 253 salivary gland tumors from a single institution in Mexico City. The 85 Candidates for initial selection were: low grade mucoepidermoid carcinoma (MEC) (N=70 ), Acinic cell cancinoma (AciCC) (N=14), papillary cystadenocarcinoma (N=1), and adenocarcinoma NOS (N=0). Tumors with some histological features consistent with MASC (N= 17, 6.7%) were studied by immunohistochemistry for mammaglobin, STAT5, and S-100 protein and four cases were positive (1.5%), thus the diagnosis of MASC was established, and these were submitted for molecular studies for ETV6-NTRK3. Fusion gene was demonstrated in three cases, two had been erroneously diagnosed as poorly granulated AciCC, and one as low grade MEC with microcystic pattern. Female gender predominated (3:1); one occurred in the parotid, two in minor salivary glands and one in the submaxillary gland; infiltrating borders, atypical mitosis and lymph node metastases were seen in the parotideal tumor. Two patients with major salivary gland tumors are alive and well at 10 and 20 months respectively, the two patients with minor salivary gland tumors are lost. It can be concluded that is important to think in MASC in poorly granulated AciCC and low grade MEC with microcystic pattern. Immunohistochemisty studies confirm the diagnosis, preferentially supported by molecular studies. MASC may follow aggressive behavior or transform into a high grade neoplasm.

Synchronic nasopharyngeal and intraparotid warthin tumors: A case report and literature review.

Warthin tumor is the second most frequent benign salivary gland tumor after pleomorphic adenoma; it occurs almost exclusively in the parotid gland and peri-parotideal lymph nodes, although it may rarely present in other locations. It may be multicentric and bilateral in a small percentage of cases. Nasopharyngeal Warthin tumor is very rare, and the presence of a synchronic WT involving nasopharynx and parotid is an exceptional event, as it has been described only twice in the literature. In this article we report an additional case of a synchronic Warthin tumor and review the related literature. Key words:Warthin tumor, synchronic WT, multicéntrico, nasopharynx.

Expression of hormonal receptors in osteosarcomas of the jaw bones: clinico-pathological analysis of 21 cases.

BACKGROUND: Sexual hormones have an important role in many hormone-dependent tumors like breast and prostate carcinomas, and also a relationship has been found with bone metabolism and bone tumors. Some studies have demonstrated that the expression of hormonal receptors (HR) in osteosarcomas (OS) of long bones is associated with gender, histological grade, histological type, and a possibly may be connection with pathogenesis and evolution. However, to our knowledge there are no studies of HR in osteosarcomas of craniofacial bones (OS-CF). OBJECTIVE: To assess the expression of hormonal receptors in OS-CF. MATERIAL AND METHODS: Twenty one cases of OS-CF were included in this study. Clinical outcome was obtained from clinical charts. Histological sections were reviewed, and immunohistochemistry studies for estrogen, progesterone and androgen receptors were performed. RESULTS: A striking female predominance was found (2:1), with a median age of 35 years. The predominant type of OS was osteoblastic (52.4%), and histological grade was high in 86%. Follow-up was obtained in 13 cases and ranged from 6 to 118 months (median 29 months). There were 8 patients (61.5%) dead or alive with progressive disease in the last follow up. Negative expression of HR was found in 19/21 cases; one showed weak nuclear expression for estrogen receptor, and another for androgen receptor. Progesterone receptor was negative in all cases. CONCLUSIONS: OS-CF mostly affected females, most of them were of the osteoblastic type and of high grade. Hormonal expression was practically negative in osteosarcoma of craniofacial bones.

[National consensus of diagnosis and treatment of non-small cell lung cancer]. / Consenso nacional de diagnóstico y tratamiento del cáncer de pulmón de células no pequeñas.

Mexican specialists in oncology, oncologic surgery, thoracic surgery, pneumology, pathology, molecular biology, anesthesiology, algology, psychology, nutrition, and rehabilitation (all of them experts in lung cancer treatment) in order to develop the National Consensus on Lung Cancer. The consensus has been developed as an answer to the need of updated Mexican guidelines for the optimal treatment of the disease, as well as to the requirements that such guidelines be established by multidisciplinary panel, depicting the current attention given to cancer lung cases in Mexico. Thus, this paper analyses the epidemiological review, screening, diagnosis, staging, pathology, translational medicine, and the suitable therapies for early, locally advanced, and metastatic disease in the first, second, and third lines of management, as well as rehabilitation and palliative measures.

Malignant gastrointestinal neuroectodermal tumor: clinicopathologic, immunohistochemical, ultrastructural, and molecular analysis of 16 cases with a reappraisal of clear cell sarcoma-like tumors of the gastrointestinal tract.

The clinical, histologic, immunophenotypic, ultrastructural, and molecular features of a distinctive gastrointestinal tumor are described. Sixteen patients, 8 women and 8 men aged 17 to 77 years (mean age, 42 y; 63% less than 40 y) presented with abdominal pain, intestinal obstruction, and an abdominal mass. Mean tumor size was 5.2 cm (range, 2.4 to 15.0 cm). The tumors arose in the small bowel (10), stomach (4), and colon (2) and were histologically characterized by a sheet-like or nested population of epithelioid or oval-to-spindle cells with small nucleoli and scattered mitoses. Five cases showed focal clearing of the cytoplasm. Scattered osteoclast-type multinucleated giant cells were present in 8 cases. The tumor cells were positive for S-100 protein, SOX10, and vimentin in 100% of cases, for CD56 in 70%, for synaptophysin in 56%, for NB84 in 50%, for NSE in 45%, and for neurofilament protein in 14% of cases. All cases tested were negative for specific melanocytic, gastrointestinal stromal tumors, epithelial, and myoid markers. Ultrastructural examination of 5 cases showed features of primitive neuroectodermal cells with clear secretory vesicles, dense-core granules, occasional gap junctions, and no evidence of melanogenesis. EWSR1 gene rearrangement was assessed by fluorescence in situ hybridization in 14 cases. Twelve cases (86%) showed split EWSR1 signal consistent with a chromosomal translocation involving EWSR1. One case showed extra intact signals, indicating that the nuclei possessed either extra copies of the EWSR1 gene or chromosome 22 polysomy. Only 1 case showed no involvement of the EWSR1 gene. Six cases demonstrated rearrangement of the partner fusion gene ATF1 (46%), and 3 showed rearrangement of CREB1 (23%); 2 cases lacked rearrangement of either partner gene. Clinical follow-up was available in 12 patients and ranged from 1.5 to 106 months. Six patients died of their tumors (mean survival, 32 mo; 83% less than 24 mo). At last follow-up, 4 patients were alive with regional, lymph node, and liver metastases, and 2 patients were alive with no evidence of disease. The tumor described here is an aggressive form of neuroectodermal tumor that should be separated from other primitive epithelioid and spindle cell tumors of the gastrointestinal tract. The distinctive ultrastructural features and absence of melanocytic differentiation serve to separate them from soft tissue clear cell sarcomas involving the gastrointestinal tract. The designation "malignant gastrointestinal neuroectodermal tumor" is proposed for this tumor type.

Thyroid gland papillary carcinomas with "micropapillary pattern," a recently recognized poor prognostic finding: clinicopathologic and survival analysis of 7 cases.

Micropapillary carcinoma is a histologic pattern, rather than an independent entity, that has an aggressive clinical behavior regardless of location. Histologically, it is characterized by papillary cell groups in clear spaces. The micropapillary pattern in the thyroid gland has not been studied until recently but under other names such as hobnail features or oncocytic and, therefore, is poorly understood, and reported cases are few. We report the clinicopathologic features of 7 cases obtained from a cohort of 496 papillary thyroid carcinomas, which corresponds to a prevalence of 1.4%. The proportion of the micropapillary component accounted for between 5% and 20% of the tumors, was slightly more prevalent in men, correlated with the presence of lymphovascular permeation, and, in the survival analysis, showed lower survival (even at a short follow-up, 8.5 years) than conventional carcinoma without this component (P = .001); this is consistent with poor overall survival in the short term (2-5 years) reported for carcinomas with micropapillary pattern of other locations. We believe that owing to this difference in survival (>95% of patients with conventional papillary carcinoma are alive at 8.5 years versus 42% of those having at least 5% of micropapillary pattern), the micropapillary pattern should be correctly identified and stated in the pathology report when comprising at least 5% of the tumor.

Extraosseous osteosarcoma in the neck.

BACKGROUND: Extraosseous osteosarcoma arising in the head and neck region is an exceptional finding, with a few isolated cases informed in the literature. We report a new case of a large high-grade extraosseous osteosarcoma located in the neck. CASE PRESENTATION: A 74 year-old woman with a tumor on the right side of the neck was treated by complete surgical resection. The histopathological diagnosis was osteoblastic extraosseous osteosarcoma. PET-CT scan disclosed no evidence of disease in other areas. Patient received adjuvant radiotherapy and after 3 months of follow-up tumor activity was detected in the cavernous sinus and the patient died of disease one month later. CONCLUSION: Extraosseous osteosarcoma in head and neck region is exceptional, and incisional biopsy is the only method to establish a diagnosis and the one to differentiate it from other bone-producing soft tissue tumors. Surgery is the gold standard for treatment of extraosseous osteosarcoma.

Multicentric epithelioid hemangioendothelioma of bone. Report of a case with radiologic-pathologic correlation.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor of uncertain biologic behavior. Most cases come out as a single lesion of the soft tissue but also may appear in the lung, liver, and other locations. Epithelioid hemangioendothelioma of bone is an extremely rare tumor and more prevalent in the second and third decades of life; its behavior is uncertain, it most commonly is unifocal, and it affects preferentially lower extremities. In this work, we present the clinical, radiologic, and pathologic findings of a 19-year-old man with a multicentric EHE of bone that involved 3 vertebrae and developed lung metastasis.

TLE1 is expressed in the majority of primary pleuropulmonary synovial sarcomas.

Pleuropulmonary synovial sarcoma (PPSS) is a rare entity, similar to synovial sarcoma of soft tissue (STSS). There are 120 published cases of PPSS, but no studies have explored the expression of TLE1. In soft tissues, it has been proven a useful marker, but in tumors of other sites, its expression has not been explored. The main objective was to study the expression and diagnostic sensitivity and specificity of TLE1 in a group of PPSS, of which the diagnosis was corroborated by fluorescence in situ hybridization confirming t(X;18) in a tissue microarray. Immunohistochemistry including TLE1, vimentin, CD99, CD56, bcl-2, AE1-AE3, EMA, CD34, CK7, CK19, calponin, and S-100 was performed on all PPSS and on 25 control cases (five carcinomas, ten mesotheliomas, and ten thoracic sarcomas). TLE1 was positive in 11 cases (73.3%); bcl-2 and vimentin in 100%; calponin and CD56 in 26.6%; CD99, CK AE1-AE3, CK19, CK7, and EMA in 80%; and S100 negative in all. The only biphasic PPSS was positive for epithelial markers only in the epithelial component. TLE1 was negative in all control cases. TLE1 is expressed in 73% of PPSS, a value inferior to that reported in STSS, but is highly specific for PPSS. TLE1 may therefore be of value in the differential diagnosis of PPSS, but should be used in a panel of antibodies.