Solid Tumor Nests Research Articles

Factors affecting the accuracy of anti-BRAF V600E immunohistochemistry results in ameloblastomas.

There are still some controversies about the results of anti-BRAF V600E-specific antibody immunohistochemistry in ameloblastomas. This study aimed to examine the accuracy of V600E-specific antibody immunohistochemistry in detection of BRAF V600E mutation in ameloblastoma tissue sections of different ages. The BRAF V600E status of 64 ameloblastoma specimens was assessed using both Sanger sequencing and V600E-specific antibody immunohistochemistry, and the sensitivity, specificity, positive predictive value, and negative predictive value were calculated. The difference in V600E-specific antibody immunohistochemistry staining intensity among the three groups of ameloblastoma tissue blocks of different ages was evaluated by chi-square test. The consistency between V600E-specific antibody immunohistochemistry and DNA sequencing results and the V600E-specific antibody immunohistochemistry staining intensity of 15 paired newly-cut and 3-month storage sections of the same 15 ameloblastomas were also compared. For detection of BRAF V600E mutation, the V600E-specific antibody immunohistochemistry had high sensitivity (98.21% 55/56), specificity (87.5% 7/8), positive predictive value (98.21% 55/56), and negative predictive value (87.5% 7/8). Heterogeneity of the staining intensity was observed in the same tissue section, but all or none expression pattern was noticed in the solid tumor nests. The storage time of paraffin tissue blocks ranging from 2 to 14 years did not affect the V600E-specific antibody-positive staining intensity. However, the three-month storage sections showed a significant diminishment of V600E-specific antibody-positive staining signals. The BRAF V600E-specific antibody immunohistochemistry is suitable for routine detection of BRAF V600E mutation in ameloblastomas. The all or none expression pattern suggests the BRAF V600E mutation may be an early event in the pathogenesis of ameloblastoma.

Breast carcinoma with osteoclast-like giant cells: A cytological-pathological correlation with a literature review.

Breast carcinoma with osteoclast-like giant cells (OGCs) is a rare disease characterized by the infiltration of OGCs in the tumor; however, cytological aspects of this tumor type remain elusive. We examined the cytological features in fine needle aspiration (FNA) biopsy smears obtained from 5 patients who were histologically diagnosed with breast carcinoma with OGCs. We compared FNA and clinicopathological findings with results from the published literature. Histological assessment of the resected samples showed that all tumors exhibited a histological grade 1 phenotype with a predominant cribriform architecture. Four patients were estrogen receptor positive, and 1 patient showed a triple negative phenotype. All patients survived without tumor recurrence. In the FNA smears, tumor cells were arranged in loosely cohesive clusters, characterized by varying degrees of OGCs infiltration and rare formation of solid tumor nests. Occasionally, 2- or 3-dimensional clusters of tumor cells were found, accompanied by OGCs at the peripheral regions. In all patients, tumor cells were small without severe nuclear atypia. None of the patients showed significant background necrosis. In summary, cytological features of breast carcinoma with OGCs are characterized by loose aggregates of low grade tumor cells, the presence of OGCs, and the absence of necrosis, all of which were consistent with features reported previously. This peculiar form of breast tumors should be included in the differential diagnosis, when physicians encounter FNA findings including low grade ductal carcinoma with the admixture of multinucleated giant cells or OGCs.

Notch as a Possible Cell Differentiation Factor in Pleomorphic Adenomas.

The expression of Notch in 30 cases of pleomorphic adenoma was examined by immunohistochemistry. Comparing the results of our study with previous literatures, from the partial CK7 expression and substantial Notch expression in ductal epithelial cells as well as the Notch expression in solid tumor nests, it can be inferred that Notch is involved in cell differentiation. CK13 expression was observed in cells undergoing squamous metaplasia and Notch expression was seen in the nucleus of basal and squamous cells. The intense Notch expression in basal cells and weak expression in squamous cells suggests that Notch is involved in the differentiation from basal to squamous cell. Moreover, the loss of nuclear expression on the inner layer would signify that differentiation is about to end or has been terminated. Notch was expressed in the cytoplasm of cartilage cells and in the cell membrane of mucous cells but not in the nucleus indicating that differentiation has been concluded. Notch involvement is suspected in cell differentiation in areas showing ductal structures and squamous metaplasia. In summary, Notch is involved in cell differentiation of ductal cells in PA. Nuclear expression was shown in tumor cells in solid nests and surrounding structures. Moreover, Notch is expressed by basal cells undergoing squamous metaplasia suggesting the participation of Notch in cell differentiation in PA.

Wnt signaling as a possible promoting factor of cell differentiation in pleomorphic adenomas.

There are well known that Wnt signaling was some roles of cell differentiation at the development tissues, especially the oral and maxillofacial regions of some developmental stages. Therefore, to determine Wnt signaling in the pleomorphic adenoma tissues, we examined. The expression of Wnt1 and β-catenin as well as the distribution of various cytoskeletal proteins CK7 and CK13 was examined in 30 cases of pleomorphic adenoma by immunohistochemistry. Wnt1 was detected in almost all tumor cells. The peripheral columnar cells in squamous metaplasia and small cuboidal cells in duct-like structures were strongly positive to Wnt1. Although β-catenin was clearly localized on the cell membrane of tumor cells, nuclear translocation was observed in small cuboidal cells and in some basaloid cells. The immunofluorescent staining pattern of Wnt1 and CK7 as well as Wnt1 and CK13 was consistent with IHC results. Thus, in pleomorphic adenoma, Wnt is involved in tumor cell differentiation of peripheral columnar cells forming solid nests and small peripheral columnar cells forming duct-like structures. Moreover, among the three currently known Wnt pathways, β-catenin is the suggested pathway working during cell differentiation. Furthermore, peripheral columnar cells in solid tumor nests and in squamous metaplasia are governed by another Wnt pathway other than β-catenin. Therefore, Wnt signaling through β-catenin pathway may be involved in the 'mixed' differentiation characteristic of pleomorphic adenoma although another pathway may also be possibly working in other parts of the tumor tissue.

New pathologic entities in penile carcinomas: an update of the 2004 World Health Organization Classification

Most primary malignant tumors of the penis are squamous cell carcinomas (SCC) of the usual type. In recent years several variants, each with distinctive clinicopathologic features, have been described. Pseudohyperplastic carcinoma and carcinoma cuniculatum are both low-grade, extremely well-differentiated SCC variants characterized by an indolent clinical course and good prognosis. The former, which may be confused with pseudoepitheliomatous hyperplasia, preferentially affects the inner foreskin mucosa of elderly men and the latter is a verruciform tumor with an endophytic, burrow-like pattern of growth. Pseudoglandular carcinoma (featuring solid tumor nests with extensive central acantholysis simulating glandular lumina) and clear cell carcinoma (human papillomavirus [HPV]-related tumors composed of periodic acid-Schiff positive clear cells) are aggressive tumors with a high incidence of inguinal nodal metastases. Papillary carcinomas are HPV-unrelated verruciform tumors composed of complex papillae with acanthosis, hyper- and parakeratosis, absence of koilocytes, irregular fibrovascular cores, and jagged tumor base. Finally, in warty-basaloid carcinomas areas of warty (condylomatous) and basaloid carcinomas coexist in the same tumor, either separated or intermingled, giving the tumor a variegated appearance. In this review special emphasis is given to the differential diagnosis of these special variants with a discussion of the possible implications for clinical management.

Thyroid papillary carcinoma with solid sclerosing change in IgG4‐related sclerosing disease

IgG4-related sclerosing disease (IgG4-RSD) is an inflammatory and fibrosing disorder characterized by lymphoplasmacytic inflammation with infiltration of various organs, including the pancreas, bile ducts, lung, kidney, and retroperitoneum. As for malignancy in IgG4-RSD, only limited literature is available. We report here a case of thyroid papillary carcinoma showing unique morphology in IgG4-RSD. Solid tumor nests were surrounded by dense IgG4-positive plasma cells and fibrosis at both the primary site and metastatic lymph nodes. In contrast the background thyroid showed focal lymphocytic thyroiditis. IgG4-related sclerosing sialadenitis and autoimmune pancreatitis were also diagnosed, and prednisolone treatment improved symptoms and serum IgG4 abnormality. To the best of our knowledge, this is the first documentation of a malignancy of the thyroid gland occurring in a background of IgG4-RSD. A brief review of the literature on the relationship between IgG4 and malignancy is included.

Large cell neuroendocrine carcinoma of the tongue base: case report of an unusual location with immunohistochemical analysis

A case of large cell neuroendocrine carcinoma (LCNEC) of the tongue base is described. It was characterized by solid tumor nests with central necrosis and rosette formation resembling basaloid squamous cell carcinoma. Immunohistochemical examination revealed that this tumor had neuroendocrine differentiation. It was diagnosed as LCNEC of the tongue base. Pulmonary LCNEC is a well-established entity, but LCNEC also occurs in other organs. This is the first report of mucosal LCNEC in the oral cavity. Basal cells in the normal squamous epithelium around the tumor indicated positivity for neural cell adhesion molecule and N-cadherin. These cells were considered neuroendocrine-related cells in the lingual squamous epithelium, which are related to the tumorigenesis of mucosal LCNEC in the tongue base.

A rare case report of mandibular metastasis of hepatocellular carcinoma: autopsy, immunohistochemical, and ultrastructural examination with literature review

A rare case of hepatocellular carcinoma (HCC) that metastasized to the posterior mandible of a 74-year-old Japanese female is described. Computed tomography (CT) revealed buccolingual osteolytic masses. Histopathologically, the solid tumor nests were composed of cells with granular eosinophilic cytoplasm, oval nuclei and enlarged nucleoli. Immunohistochemically, the tumor cells were strongly positive for hepatocyte paraffin 1 (Hep Par 1) and cytokeratin 18 (CK18). Ultrastructurally, abundant mitochondria, rough endoplasmic reticulum, lysosome-like granules, ductal structures and intercellular junctional complexes were distinct in the tumor cells. At autopsy, multinodular tumor masses and cirrhosis were detected in the liver. Microscopically, the tumor cells had trabecular, solid and sarcomatous appearances with severe atypism. Metastatic foci were found in the spleen, stomach, lymph nodes and ribs, but not in the lungs. We finally diagnosed this as mandibular metastasis of HCC, which is a very rare cancer, 1 of only 5 known cases in a female.

Syringoid eccrine carcinoma with apparently aggressive transformation: case report and review of the literature

A 65-year-old man presented with a 20-year history of a lesion on his lower abdomen. The lesion had started as an indolent papule that slowly developed to form an extensive plaque. Physical examination revealed a flat-topped, elevated, well-demarcated, erythematous plaque measuring 7 cm × 5 cm in diameter (Fig. 1). The lesion had an elastic, hard induration beneath the plaque and was fixed to the underlying tissue. Inguinal lymphadenopathy was present. Hematologic and biochemical investigations were all within the normal ranges. The patient underwent incision biopsy. Figure 1. Clinical appearance of the lesion. An indurated plaque can be seen on the lower abdomen Download figure to PowerPoint A biopsy specimen, measuring 2.7 cm, revealed that the tumor was located in the dermis, and consisted of solid nests and small cords in a dense fibrocollagenous stroma. The tumor located in the upper dermis consisted mainly of solid nests with calcified central necrosis (Figs 2 and 3). The tumor located in the deep dermis consisted of small cords forming luminal, tubular, and tadpole-shaped structures, resembling those of syringoma (Figs 2 and 3). Solid tumor nests consisted of tumor cells which were basaloid and polymorphic, with hyperchromatic nuclei. A few mitotic figures were observed. A palisading arrangement of tumor cells was not observed at the periphery of the solid tumor nests. Keratinous cysts and follicular differentiation were not observed. No apocrine differentiation, such as decapitation secretion, was observed. There were no connections between the tumor nests and the epidermis. The extent of tumor invasion could not be determined from the biopsy specimen because the tumor had spread beyond the edges of the excision. Immunohistochemical analysis showed diffuse nuclear and cytoplasmic positivity for S-100 protein (1 : 1000; Dakopatts, Glostrup, Denmark) and focal positivity for carcinoembryonic antigen (CEA, 1 : 500; Mochida, Tokyo, Japan). Figure 2. The tumor consisted of solid undifferentiated nests and small cords forming tubular structures in a dense fibrocollagenous stroma (original magnification, ×40) Download figure to PowerPoint Figure 3. The tumor located in the upper dermis consisted mainly of solid undifferentiated nests with calcified central necrosis. Small cords forming tubular structures resembling those of syringoma can also be observed (original magnification, ×200) Download figure to PowerPoint The extent of tumor spread was evaluated by computed tomography (CT) and magnetic resonance imaging. The primary tumor had infiltrated the rectus abdominis muscle, and multiple metastases, up to 1 cm in diameter, were observed in the lungs, right bronchus, para-aortic lymph nodes and Th11, right S1, and bilateral ilium. CT scan revealed no continuity between the tumor and the prostate. After consulting a urologist, the possibility of prostate cancer was ruled out. After diagnosis and evaluation of tumor spread, the patient was treated with seven cycles of combination chemotherapy as follows: 5-fluorouracil (350 mg/m2 intravenously) on days 1–5, epirubicin (40 mg/m2 intravenously) on day 1, mitomycin C (3.5 mg/m2 intravenously) on day 1, vincristine sulfate (0.7 mg/m2 intravenously) and carboplatin (300 mg/m2 intravenously) on day 2, every 21–28 days. The treatment was relatively well tolerated without major complications. After seven courses of chemotherapy, evaluation by CT showed no change in the size of the primary lesion, or in the size and number of distant metastases. It is now 6 months since the last course of treatment and the patient appears to have stable disease.

Ｍａｌｉｇｎａｎｔ ｅｃｃｒｉｎｅ ｐｏｒｏｍａの１例

A case of malignant eccrine poroma is reported. The patient, a 73-year-old woman, had a granulomatous tumor on her right sole during the last 10 years. Histological examination revealed solid tumor nests were composed of mainly poroma like cells. However, some of them were atypical cells suggested malignant tumor. Immunohistochemical studies showed that tumor cells, around the duct like structures, were especially stained with anti-CEA antibody.

Inverted Follicular Keratosis and Papillomavirus Infection

This report describes a case of inverted follicular keratosis in a keratotic nodule found on the thigh of a 58-year-old man. The upper surface of the nodule was papillary, while the lateral aspect was smooth with columnar structures. Histologically, the lesion exhibited primarily exophytic growth, although there was some endophytic growth. There were multiple closely approximated columnar solid tumor nests. Many of these columnar tumor nests had a central funnel-shaped plug of dense parakeratotic keratinous material. The tumor nests were composed of peripheral smaller basaloid cells and central squamoid cells forming squamous eddies. Inflammatory lymphocytic cell infiltration and lytic change were found mainly at the base of the tumor. Several hair follicles transversed the tumor. Ballooning alteration of granular cells and vacuolated keratinocytes, especially within areas of hypergranulosis, were observed in each of the columnar tumor nests. Some cells with ballooning alteration were recognized by papillomavirus common antibody. Ultrastructurally, vacuolated keratinocytes exhibited cytoplasmic vacuoles containing keratohyaline composite granules. Compound structures of membrane-coating granules, which have been associated with outer root sheath keratinization, were noted. The case therefore represents an inverted follicular keratosis manifesting as a distinct hair follicle tumor related to prior infection by papillomavirus.

Significance of histologic grading in the prognosis of ovarian tumors.

The prognostic significance of a histologic grading system was studied by an analysis of pathological specimens from 73 patients with ovarian epithelial cancers and tumors of borderline malignancies (tumors of low malignant potential) collected over a period of 25 years. The survival probability of patients in each group was analyzed by a computer program based on the product limit of Kaplan and Meier. The histologic grading scheme based on the presence of papillary formations or glands versus the presence of solid tumor nests proved to be prognostically significant for patients with stage I and II disease. The other grading system, based on cytologic features, was able to stratify survival rates into three instead of two groups distinguished by the histologic grading system. The survival of patients with moderately and poorly differentiated tumors was essentially the same. No difference was found between the prognoses of patients with cytologic grades 3 and 4.