Metaplastic Breast Cancer Masquerading as Liposarcoma of the Breast: A Case Report following Oncoplastic Treatment.

Mammary liposarcoma is among the rarest of breast tumours. Here we report the presentation, macroscopic, microscopic, and immunohistochemical features of an extremely rare case of metaplastic carcinoma with extensive pleomorphic liposarcomatous differentiation. A 47-year-old woman presented with bilateral grade III breast ptosis and a 3 × 4 cm mass in the lower outer quadrant of the left breast. Mammography and ultrasound confirmed a well-defined mass. A core biopsy performed was diagnosed as pleomorphic liposarcoma. Microscopically, this was a well-defined, lobulated tumour comprising solid sheets of large pleomorphic and spindle cells with bizarre forms, vacuolated cytoplasm, and ample mitoses. Atypical lipoblasts were easily identifiable. Due to the strong, though patchy, cytokeratin expression, the diagnosis of metaplastic carcinoma with pleomorphic liposarcomatous differentiation was made. Extensive sampling, careful search for a biphasic pattern, ductal carcinoma in situ, and/or epithelial differentiation, and a panel of broad-spectrum cytokeratins are essential to establish the diagnosis.

Lingual adaptations of the Tarentola annularis with new insights into its papillary system adaptations: Ultrastructure, histochemistry, and immunohistochemical observations.

Our research aims to conduct a comprehensive ultrastructural, histochemical, and immunohistochemical examination of Tarentola annularis' tongue, utilizing various techniques such as light, scanning electron microscopy, and morphometric analysis. The complex papillary system consisted of four conical subtypes and one filiform type. The apex carried three conical subtypes (elongated, quadrilateral, and round); the midtongue carried two papillary types (quadrilateral conical and rectangular pointed filiform); and the hindtongue carried two conical subtypes (quadrilateral and elongated serrated). The dorsal papillary surface carried little taste pores on the foretongue and taste buds on the midtongue. The foretongue had a slightly stratum corneum that spread to coat the papillae, while the mid- and hindtongue did not. The glands are absent from the foretongue but are found in the interpapillary spaces of the mid- and hindtongue. Histochemical analysis reveals the presence of collagen fibers in the muscle bundles and the papillary core. The midtongue glands exhibited a strong reaction to AB and PAS, while the hindtongue showed moderate AB positivity and strong positive PAS. The cytokeratin expression in the foretongue papilla was positive, whereas the papillae in other regions were negative. The Tarentola annularis exhibits distinctive lingual structural characteristics due to its varied feeding habits influenced by available food particles.

Epithelioid and spindle cell rhabdomyosarcoma with EWSR1::TFCP2 fusion mimicking metastatic lung cancer: A case report and literature review.

Rhabdomyosarcoma (RMS) with EWSR1/FUS::TFCP2 fusion is an emerging, molecularly defined, rare subtype of RMS. It can affect patients in a wide age range and follows an aggressive clinical course according to the reported cases. Due to its unusual clinical and pathohistological features, with a typical intraosseous presentation and common cytokeratin expression, the diagnosis is challenging, and metastatic undifferentiated/sarcomatoid carcinoma can be an important differential diagnosis. We report here a case of a 55-year-old woman with an RMS with EWSR1::TFCP2 fusion mimicking metastatic lung cancer in view of the clinical and microscopic presentation. However, further molecular workup, including RNA sequencing, led to the proper diagnosis. Although these tumors are rare, knowledge of their unique features is essential for correct diagnosis as a basis for clinical management and optimization of therapeutic approaches.

Sialyl LewisX/A and Cytokeratin Crosstalk in Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) encompasses multiple entities and is generally highly aggressive and metastatic. We aimed to determine the clinical and biological relevance of Sialyl-Lewis X and A (sLeX/A)-a fucosylated glycan involved in metastasis-in TNBC. Here, we studied tissues from 50 TNBC patients, transcripts from a TNBC dataset from The Cancer Genome Atlas (TCGA) database, and a primary breast cancer cell line. All 50 TNBC tissue samples analysed expressed sLeX/A. Patients with high expression of sLeX/A had 3 years less disease-free survival than patients with lower expression. In tissue, sLeX/A negatively correlated with cytokeratins 5/6 (CK5/6, which was corroborated by the inverse correlation between fucosyltransferases and CK5/6 genes. Our observations were confirmed in vitro when inhibition of sLeX/A remarkably increased expression of CK5/6, followed by a decreased proliferation and invasion capacity. Among the reported glycoproteins bearing sLeX/A and based on the STRING tool, α6 integrin showed the highest interaction score with CK5/6. This is the first report on the sLeX/A expression in TNBC, highlighting its association with lower disease-free survival and its inverse crosstalk with CK5/6 with α6 integrin as a mediator. All in all, sLeX/A is critical for TNBC malignancy and a potential prognosis biomarker and therapeutic target.

Cytologic features of an acanthomatous ameloblastoma in a dog.

An 8-year-old mixed breed male dog was presented with a mass on the rostral mandibular gingiva that quickly emerged 2-3 weeks prior to presentation. The mass was firm, smooth, well-circumscribed, and approximately 2 × 1 × 0.5 cm in size rostral to the left mandibular canine tooth (304). Clinical examination and radiographs were unremarkable. Cytology revealed two distinct cell populations, consisting of numerous uniform-appearing epithelial cell clusters and low numbers of individual spindle cells. Epithelial cells had mild anisocytosis and anisokaryosis, round nuclei with finely stippled chromatin, no prominent nucleoli, high N:C ratios, and low amounts of pale basophilic cytoplasm. Slender spindle cells observed had oval nuclei with no prominent nucleoli and wispy cytoplasm. On histopathologic examination, the lamina propria of the gingiva was dissected by numerous irregular and anastomosing trabeculae and islands of neoplastic epithelial cells. Neoplastic cells were focally in connection with the hyperplastic overlying epithelium. The trabeculae were surrounded and embedded by cell-rich fibrous stroma. Peripheral to the islands and trabeculae, cells were arranged in palisades, and the nuclei had an antibasilar location. The epithelial cells had prominent intercellular bridges, low amounts of cytoplasm, and one round to oval nucleus. Anisocytosis and anisokaryosis were mild to moderate, and six mitoses/10 HPF were present. Tumor cells reached the deep sample margins. Histopathologic evaluation was consistent with acanthomatous ameloblastoma. This locally aggressive neoplasm causes alveolar bone lysis and often extends beyond alveolar bone margins. Acanthomatous ameloblastoma is an important differential for rostral mandibular gingival masses containing numerous uniform epithelial cell clusters with rare slender spindle cells.

Single-Cell RNA Sequencing of a Postmenopausal Normal Breast Tissue Identifies Multiple Cell Types That Contribute to Breast Cancer.

The human breast is composed of diverse cell types. Studies have delineated mammary epithelial cells, but the other cell types in the breast have scarcely been characterized. In order to gain insight into the cellular composition of the tissue, we performed droplet-mediated RNA sequencing of 3193 single cells isolated from a postmenopausal breast tissue without enriching for epithelial cells. Unbiased clustering analysis identified 10 distinct cell clusters, seven of which were nonepithelial devoid of cytokeratin expression. The remaining three cell clusters expressed cytokeratins (CKs), representing breast epithelial cells; Cluster 2 and Cluster 7 cells expressed luminal and basal CKs, respectively, whereas Cluster 9 cells expressed both luminal and basal CKs, as well as other CKs of unknown specificity. To assess which cell type(s) potentially contributes to breast cancer, we used the differential gene expression signature of each cell cluster to derive gene set variation analysis (GSVA) scores and classified breast tumors in The Cancer Gene Atlas (TGGA) dataset (n = 1100) by assigning the highest GSVA scoring cell cluster number for each tumor. The results showed that five clusters (Clusters 2, 3, 7, 8, and 9) could categorize >85% of breast tumors collectively. Notably, Cluster 2 (luminal epithelial) and Cluster 3 (fibroblast) tumors were equally prevalent in the luminal breast cancer subtypes, whereas Cluster 7 (basal epithelial) and Cluster 9 (other epithelial) tumors were present primarily in the triple-negative breast cancer (TNBC) subtype. Cluster 8 (immune) tumors were present in all subtypes, indicating that immune cells may contribute to breast cancer regardless of the subtypes. Cluster 9 tumors were significantly associated with poor patient survival in TNBC, suggesting that this epithelial cell type may give rise to an aggressive TNBC subset.

Analysis of human nasal mucosal cell sheets fabricated using transported tissue and blood specimens.

Previously, we succeeded in transplanting autologous nasal mucosal cell sheets in the middle ears of 5 patients, who underwent cholesteatoma resection, which prevents recurrence of cholesteatoma in clinical settings. Current good manufacturing practice (GMP) standards for human cell cultivation requires the establishment of cell processing centers (CPC) which act as germ-free facilities. However, due to practical difficulties involved in establishing and maintaining such facilities at each individual hospital, a functional transport system is felt to be needed for the continuation of effective regenerative therapy. In the current study, nasal mucosal tissue and autologous blood obtained from 3 human volunteers were transported for over 3 h. Disinfected nasal tissues were cultured using keratinocyte culture medium, which included autologous serum prepared from blood. After 24 d, cultured nasal mucosal cells were transported for over 3 h and subsequently assessed for cell number, viability and purity. Moreover, CK4, CK8, and CK18 were analyzed the suitability of these nasal mucosal cell sheets for middle ear regenerative therapy. Overall, we confirmed that nasal mucosal cell sheets can be fabricated using transported nasal mucosal tissue and blood. This study would be contribute to establish a new regenerative therapy for clinical application, accompanied with transportation between companies and hospitals.

Morphologic shift associated with aberrant cytokeratin expression in a GIST patient after tyrosine kinase inhibitors therapy. A case report with a brief review of the literature.

After an initial benefit from tyrosine kinase inhibitors (TKI), most gastrointestinal stromal tumors (GISTs) eventually develop disease progression or secondary resistance. An altered tumor (immune)phenotype with anaplasia and morphological changes secondary to therapy have occasionally been described in the literature. We present a 52-year old patient, diagnosed with high risk, spindle-cell, GIST (CD117 positive, Pankeratin negative) in 2003, showing a c-Kit exon 11 mutation. After TKI therapy, he developed drug resistance and disease progression. Pathological assessment of the last surgical specimen showed a pure epithelioid/clear cell histology, without evidence of cellular anaplasia. Tumor cells were CD117 positive, DOG1 positive but also E-cadherin positive and Pankeratin positive, whereas molecular analysis confirmed the presence of the c-Kit exon 11 mutation, with no additional mutations. We describe an unusual case of GIST showing peculiar (immuno)phenotypic changes under therapy, different from the vast majority of therapy-driven changes, which include marked cellular pleomorphisms and KIT immunonegativity. Possible molecular explanations to understand these phenomena and a brief review of the literature are also addressed.

Cytopathological Features of a Severe Type of Corneal Intraepithelial Neoplasia.

PURPOSE: To report the cytopathological features of corneal intraepithelial neoplasia (CIN) through the investigation of cytokeratin expression pattern, keratinization, cell proliferation, apoptosis, and epithelial mesenchymal transition. PATIENT AND METHODS: Corneal tissue excised from a CIN patient was examined in this study. Cryosections of the excised CIN epithelial tissue were examined by immunostaining analysis using antibodies against cytokeratins, keratinization-related proteins, Ki-67, human telomerase reverse transcriptase (hTERT), and epithelial mesenchymal transition (EMT)-related proteins. Subcellular localization of F-actin was also analyzed using phalloidin. For the detection of apoptotic cells, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed. Real-time polymerase chain reaction was performed to quantify the expression level of hTERT in the CIN epithelium. RESULTS: The CIN epithelium exhibited a significantly altered cytokeratin expression pattern compared to normal corneas with an upregulated expression of keratinization-related proteins. The CIN epithelium also demonstrated an increased number of Ki-67-positive cells with an upregulated expression of hTERT, while exhibiting an increased number of apoptotic cells. EMT did not occur in the CIN epithelium. CONCLUSION: CIN epithelium seems to be slightly dedifferentiated from the corneal epithelial lineage. The status of cell proliferation and apoptosis in the CIN epithelium was significantly altered from that of normal corneal epithelium, but its malignancy level does not appear to be as high as that of metastasis-competent malignant cancers.

Cytokeratin Expression at Different Stages in Sweat Gland Development of C57BL/6J Mice.

Sweat glands exhibit a documented role in epidermal reepithelialization after wounding. However, the regenerative potential of sweat glands has remained underappreciated due to the absence of useful markers for the analysis of determination and differentiation processes in the developing eccrine sweat gland from epithelium. Although the current knowledge of keratin expression in most of the different origins has been described, it remains widely shared and not unified in eccrine sweat glands of C57BL/6J mice that are commonly used as animal models for sweat gland and wound healing studies, both at the molecular and cellular levels. Aiming to answer this question, we have investigated the changes in cytokeratin expression patterns during the embryonic, neonatal, juvenile, and young adult stages (E12.5, E17.5, P0.5, P5, and P28). In this article, we demonstrate that the morphology of murine sweat gland progenitor cells are similar to epidermal stem cells before birth (E12.5 and E17.5); at postnatal stages, the duct formed gradually and curled to glob. K8 and K19 were expressed in the eccrine sweat gland cells at all times and highly expressed after birth at both gene and protein levels. Also, histological results revealed K8 and K19 positive cells localized in the secretary portion of glands. Meanwhile, K14 strongly expressed both in vivo and in vitro at E12.5, while it weakly expressed at other stages. Moreover, K10 was rarely detected before birth, but it expressed positively in vivo and in vitro only at the protein level after birth. These data indicate the pattern of main cytokeratin expression at different stages during murine sweat gland development and might provide an efficient tool for sweat gland research and exciting potential for developing targeted therapies for wound healing.

A Peripheral Dentinogenic Ghost Cell Tumor With Immunohistochemical Investigations and a Literature Review-Based Clinicopathological Comparison Between Peripheral and Central Variants.

The aim of the study was to present a peripheral dentinogenic ghost cell tumor (DGCT) and to describe clinicopathological differences between peripheral and central variants of the tumor using a selected literature review. The case report is based on a swelling present on the alveolar ridge of a 74-year-old edentulous denture wearer. The lesion was diagnosed as a peripheral DGCT after excluding the presence of a central lesion. Immunohistochemical investigations revealed similar cytokeratin expression pattern, with CK14 and MNF116 positivity in both the tumor and the surrounding surface epithelium. However, in contrast, CK19 expression was restricted to less than 5% of the tumor cells. A clinicopathological comparison was compiled using 30 cases of peripheral DGCTs (including the present lesion) and 16 cases of central DGCTs published over a period of 40 years. Accordingly, peripheral lesions were more often found in elderly denture wearers, in relation to mandibular gingiva and alveolar mucosa. None of the lesions had recurred after excision. In contrast, majority of the central lesions were common in younger individuals and showed a striking male predilection. It occurred equally on both jaws, while approximately 50% of the lesions gave rise to recurrences. In conclusion, similar cytokeratin expression in both the tumor and surface epithelium can be used to support oral surface epithelial origin, while CK14 positivity confirms the odontogenic derivation of the peripheral DGCT described in the report. In contrast to central DGCT, the peripheral DGCT is a distinct lesion with characteristic clinicopathological profile and nonaggressive behavior.