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.

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.

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.

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.

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.

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.

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.

Necrotizing sialometaplasia of the palate associated with angiocentric T-cell lymphoma.

In this article we present 2 cases of necrotizing sialometaplasia (NS) associated with angiocentric lymphoma of the midline. Immunohistochemical analysis confirmed a T-cell origin, and in situ hybridization in one case revealed its relationship to Epstein-Barr virus. These findings suggest that vascular occlusion by the neoplastic cells produces ischemia, which leads to local infarction contributing to the salivary gland lesion. To our knowledge, the association between angiocentric lymphoma and NS has been previously reported in only one instance, and we suggest that this particular type of lymphoma should be added to the list of related conditions for NS.

Primary extracranial meningioma of the mandible.

Meningiomas are benign tumors of mesodermal origin that arise from arachnoid cell clusters that penetrate the dura to form arachnoid villi. These neoplasms represent one of the most common neoplasms developing within the central nervous system and are usually located at points of entry of vessels and nerves through the dura. Extracranial meningiomas (EM) comprise only 2% of all meningiomas, and only six cases of primary EM of the jawbones have been described to date. They may arise as an extension of intracranial meningiomas or as primary tumors and may be clinically indistinguishable from other benign tumours of the jaws, as they usually present as a well-delineated unencapsulated tumors. In this article a case of primary intramandibular primary EM that appeared as a well-defined osteolytic radiolucent lesion of the jaw is reported. The salient clinico-pathological features of this case is compared to those previously reported in the literature and differential diagnosis and therapeutic considerations are discussed.

Odontogenic myxoma: clinico-pathological, immunohistochemical and ultrastructural findings of a multicentric series.

The aim of this study was to analyze the clinico-pathological and immunohistochemical features of 62 cases of odontogenic myxoma (OM) diagnosed in three Oral Pathology Diagnostic Services in Latin America, as well as to describe the ultrastructural features of three of these cases. OM showed a wide age range (9-71 years), with a mean of 27.97 yr (SD: 11.01) and a male to female ratio of 1:2.2. Mandible was affected in 37 cases (59.6%) and maxilla in 25 (40.4%), with 61.3% located in the posterior region. Thirty-nine cases (62.9%) were multilocular and 23 (37.1%) unilocular. Size ranged from 1 to 13 cm, (mean: 5.2 cm). Thirty-seven multilocular (54.8%) and 6 unilocular lesions (26%) were larger than 4 cm (p<0.05). Epithelial islands were identified in 5 cases (8%) on H&E stained sections, but AE1/AE3 and CK14 disclosed these structures in 15 cases each (24.2%); CK5 was positive in 8 (12.9%); CK7 in 2 (3.2%) and CK19 in only 3 cases (4.8%). All cases were negative for CKs 8 and 18, S-100 protein, NSE and CD68, and showed a low index of expression of Bcl2 and ki-67 proteins (<1%). Mast cell antibodies showed these cells in 45 cases (72.6%). Myofibroblastic differentiation evidenced by myofilaments and fibronexi was found in one case out of the three studied by TEM and 29 cases (46.7%) were positive by immunohistochemistry for alpha actin. In conclusion, only a minority of OM had epithelial islands, and only 3 cases expressed CK 19, indicating an odontogenic epithelium origin. Immunohistochemical and ultrastructural findings suggest that OM is a mesenchymal neoplasm in which several factors may contribute to its pathogenesis, including myofibroblastic differentiation and the participation of mast cell products. However, further investigations are needed to better understand the participation of these elements in this particular neoplasm.

Histomorphological evaluation, cell proliferation and endothelial immunostaining in oral and maxillofacial myofibroblastic lesions

Background: Myofibroblasts (MF) are mesenchymal cells with features of both fibroblasts and smooth muscle cells. Although these are usually reactive cells, they can lead to myofibroblastic tumors that may share clinical and histomorphological characteristics but with different prognosis. The aim of this study is to perform a histomorphological evaluation as well as to compare and evaluate two different cell proliferation immunomarkers and two endothelial markers in a group of oral and maxillofacial myofibroblastic lesions (MFL). Material and methods: Cross-sectional and retrospective study. Demographic, clinical, histomorphological and immunohistochemical characteristics of 39 cases of MFL were analyzed. Immunohistochemical reactions were performed with the Ki67, MCM2, CD34 and CD105 antibodies. Kruskal-Wallis test and Spearman correlation analysis were used. Results: Four cases of nodular fasciitis (NF), 18 myofibromas (My), 6 desmoplastic fibromas (DF), 7 inflammatory myofibroblastic tumors (IMT) and 4 myofibroblastic sarcomas (MFS) were studied. There were twenty women (51.2%); the median age was 13 [Q1-Q3: 8-24] years and most cases occurred in the mandible (48.7%). A statistically significant difference with MCM2 immunostaining (p=0.0221) was observed between the MFL; furthermore, a correlation between CD34 and CD105 immunostaining in NF (p <0.0001) and IMT (p=0.0408), between MCM2 and CD34 in IMT (p=0.0362) and between MCM2 and CD105 in MFS (p <0001) were found. Conclusions: MCM2 immunostaining could assess more clearly the cell growth fraction in MFL. The correlation between MCM2 and CD34 in IMT and between MCM2 and CD105 in MFS are indicative of the high activity of these lesions. These results emphasize the importance of the studied immunohistochemistry markers as possible tools for a better characterization of some of the MFL. (AU)

Dermatofibroma and dermatofibrosarcoma protuberans: a comparative ultrastructural study.

Dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) are dermal tumors whose histogenesis has not been well defined to date. The differential diagnosis in most cases is established in routine H/E sections and may be confirmed by immunohistochemistry, but there are atypical variants of DF with less clear histological differences and non-conclusive immunohistochemical results. In those cases, electron microscopy studies may be useful in establishing the diagnosis. The authors describe in detail the ultrastructural characteristics of 38 cases of DFSP and 10 cases of DF. The objective was to establish the ultrastructural features for differential diagnosis, and to identify the possible histogenesis of both neoplasms. DFSP is formed by stellate or spindled cells with long, slender, ramified cell processes joined by primitive junctions. Subplasmalemmal densities were frequently seen in the processes. Another common finding was the presence of multivesicular buds (MVB), peculiar structures that contain microvesicles abutting from the cell membrane. In contrast, DF is characterized by a proliferation of multiple capillary vessels with prominent endothelium and a perivascular population of ovoid or spindled cells devoid of cell processes. These latter cells featured intracytoplasmic lipid material (p < .001), infrequent subplasmalemmal densities (p < .001), and absence of MVB (p < .001). With the ultrastructural characteristics and the constant expression of CD34 in DFSP, a probable origin in dermal dendrocytes is postulated for this tumor. The histogenesis of DF is less clear, but an origin from FXIIIa modified perivascular dermal dendrocytes is proposed.

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.

eIF4E as a marker for cervical neoplasia.

Eukaryotic translation initiation factor 4E (eIF4E) is upregulated in cancers of the breast and head and neck. The authors have shown that eIF4E is increased in cervical neoplasia and that eIF4E upregulates human papillomavirus (HPV) oncoprotein E7. The aim of this study was to quantitate eIF4E in tissues representing a wide range of cervical pathology. The potential correlation between dysplastic grade or tumor stage with eIF4E upregulation and/or HPV genotype was analyzed for 10 normal, 27 cancer, and 37 dysplasia cases. A progressive increase in eIF4E staining intensity was found with increasing cervical pathology (P < 0.0001). No difference was seen in eIF4E stain intensity by either tumor type--squamous cell cancer (n = 18), adenocarcinoma (n = 4), or other types of cancer (n = 5) (P = 0.97)--or by tumor grade--II (n = 5) versus III (n = 7). Likewise, neither an HPV typing result of HPV 16 (n = 10) versus non-HPV 16 (n = 4) nor single HPV infection (n = 11) versus dual HPV infection (n = 3) significantly altered the eIF4E stain results (P = 0.86 and 0.97, respectively). These results indicate that eIF4E stain intensity may be useful as a marker for cervical neoplasia.

Mediastinal germ cell tumors.

Germ Cell Tumors (GCT) represent an important group of mediastinal tumors. Because of genetic characteristics and behavior have been divided in prepubertal and postpubertal tumors, and their origin remains controversial. The genetic changes are diverse, but the most frequent is i (12p), and can be associated to gonadal disgenesis. Histological classification is similiar to that of gonadal tumors and all histological types have been described in the mediastinum. Teratomas may undergo malignant transformation with the emergence of somatic tumors such as haematological malignancies, sarcomas, carcinomas and neurogenic tumors, and such transformation may occur in the primary site or in the metastases. Prognostic factors in mediastinal germ cell tumors include: age of the patient, histological type, distant metastases, stage, status of resection, level of serum tumor markers and proliferation markers. Immunohistochemistry is especially useful when the primary GCT is occult, to separate types of immature GCT, and to determine the lineage of malignant transformation which may be important to design treatment strategies.