CK7 Immunoreactivity Research Articles

Is “Localized juvenile spongiotic gingival hyperplasia” an appropriate term? Insights based on a case series and literature review

<h3>Introduction</h3> Localized juvenile spongiotic gingival hyperplasia (LJSGH) is an entity presenting as reddish gingival enlargements microscopically exhibiting spongiotic non-keratinized epithelium with inflammatory exocytosis. To this date, various terms have been proposed, but, arguably, none of them has accurately described the clinicopatho- logic features and origin of these lesions. Additionally, insufficient emphasis has been given on their microscopic characteristics. <h3>Materials and methods</h3> Lesions with a diagnosis of LJSGH, established by histopathologic examination and CK19 immunoreactivity (in equivocal cases), were retrieved. The patients' demographic and clinical characteristics were collected. Additionally, microscopic features were assessed including the extent of spongiotic changes and epithelial surface morphology (flat vs. papillary). A review of the pertinent English language literature was conducted. <h3>Results</h3> Eighteen patients with a total of 21 biopsied lesions were identified, exhibiting a mean age of 19.2 years (range: 8-57) and a slight female predilection (10:8). The most common site of involvement was the facial maxillary gingiva (17 lesions), while 4 patients exhibited multifocal lesions. Microscopically, 16 lesions showed prominent epithelial spongiosis, while flat morphology was more common than papillary (13:8). The literature review disclosed 203 cases including those presented herein. A mean age of 14.7 years was recorded, with almost equal gender distribution (103:100, F: M), while the anterior maxilla was affected more commonly (>80% of lesions). Eighteen patients displayed multifocal lesions. <h3>Conclusions</h3> Since almost 10% of LJSGHs are multifocal, the word "localized" could be omitted. Additionally, pa- tients over 50 may be involved, hence the term "juvenile" may be also misleading. "Hyperplasia", a histopathologic term referring to increases in number of cells, does not always characterize these lesions that could occasionally display epithelial atrophy (especially the flat subtype). Finally, the entity's odontogenic origin, as supported by the resemblance to the junctional epithelium and the immunophenotypic features, may need to be emphasized.

TROP-2: a unique immunohistochemical marker for diagnosis of papillary thyroid carcinoma

Background: Histomorphology remains the gold standard in the diagnosis of thyroid tumors; specifically papillary thyroid carcinoma (PTC). However, equivocal cytohistologic features may be encountered, and warrant special criteria for distinction. Aim: This study aimed to determine the potential use of TROP-2 immunoreactivity in the diagnosis of PTC (in comparison to CK19 immunoreactivity) and its role in the segregation of PTC from non-neoplastic, benign as well as malignant thyroid lesions, and to predict the diagnostic significance of both markers in combination. Material and Methods: The current work was carried out on 249 cases of thyroid lesions, retrieved as paraffin blocks; from the Department of Pathology, Faculty of Medicine, Tanta University. The study was conducted during the period from March 2019 to May 2020. HE TROP-2 showed 100% specificity, 87.78% sensitivity, 100% PPV and 94.47% accuracy, CK19 showed 100% sensitivity, 25.69% specificity. For segregation of PTC, from other (non-neoplastic, benign or malignant) thyroid lesions; TROP-2 showed 87.78% sensitivity, 98.11% specificity, 96.34% PPV, 93.41% NPV and 94.38% accuracy. CK19 showed 100% sensitivity and 100% NPV, yet it had low specificity of 40.25%, a low PPV of 48.65% and low accuracy of 61.85%. The combined usage of both markers didn’t show better results than TROP-2 alone. Conclusions: CK19 exhibits high sensitivity over TROP-2 in PTC diagnosis, however, TROP-2 shows high specificity and better accuracy. The combination of both markers doesn't show remarkable findings than TROP-2 alone.

Ferulic acid as anticarcinogenic agent against 1,2-dimethylhydrazine induced colon cancer in rats

ObjectivesThe aim of the study was to assess the beneficial effect of ferulic acid (FA) compared to 5-flurouracil (5FU) on colon cancer caused by 1,2-dimethylhydrazine (DMH). MethodRats were divided into four groups (Control, FA, 5FU and DMH groups). The DMH group was injected subcutaneously once a week for 15 weeks. FA group was orally administered three times per week for 4 weeks with dose of 50 mg/kg. The 5FU group was intraperitoneally injected once per week with dose of 50 mg/kg for 4 weeks. ResultsHistopathological, immunohistochemical and molecular studies have been undertaken. The mucosa of the induced colon cancer was significant infiltrated by mononuclear cells and hemorrhage. Also, there was improper shape of the crypts with partial loss of polarity. The muscularis mucosa was infiltrated by pleomorphic cells. The mucosa and submucosa have indeed been invaded by a gland-like set of cells, congested blood vessels with extravagance of mononuclear cells, which are concentrated in the mucosa that fills the corium of the connective tissue. Moreover, colon sections of the DMH treated rats showed intensive immunoreactivity to Ki67, CK20 and weak immunoreactivity to P53 and Caspase-3. Moreover, FA could significantly (p < 0.01) upregulate P53 by approximately 5 fold. ConclusionsFindings of the present study indicated a significant therapeutic effect of ferulic acid against colon cancer by inhibiting proliferation and promoting apoptosis.

Merkel cells of human oral mucosa express the pluripotent stem cell transcription factor Sox2.

Merkel cells are neuroendocrine cells associated to a neural sensitive ending and localized primarily in the epidermis, although they are also found in oral mucosa. Sox2 or SRY-box2 is a key transcription factor important in the maintenance of embryonic neural crest stem cell pluripotency. Sox2 has been described in Merkel cells of skin and in Merkel cell carcinomas, but not specifically in oral Merkel cells. The aims of the present study were to analyze the density of Merkel cells in human oral mucosa and to study the expression of Sox2 in these cells. For these purposes, immunohistochemical analyses for Sox2 and CK20 (the best marker for Merkel cells) were automatically performed on sections of normal human oral mucosa. Double immunofluorescence for Sox2 and CK20 was also performed. To analyze the density of Merkel cells, CK20 positive cells were counted in each sample and the length of the epithelial apical edge was measured (cells/mm). Merkel cells, demonstrated by CK20 immunoreactivity, were found in 95% of oral mucosa specimens studied (n=21). Mean density of Merkel cells in oral mucosa was 1.71±2.34 cells/mm. Sox2 immunoreactivity was found in the nuclei of scattered cells located at the basal layer. Serial sections immunostained for Sox2 and CK20 showed that Sox2-positive cells of oral mucosa coexpressed CK20, confirming that they were Merkel cells. Immunofluorescence for Sox2 and CK20 showed colocalization of both markers, demonstrating that virtually all oral Merkel cells expressed Sox2. This transcription factor could play a role in Merkel cell maturation and maintenance.

Immunohistochemical staining patterns of Ki-67 and p53 in florid reactive urothelial atypia and urothelial carcinoma in situ demonstrate significant overlap

Flat urothelial lesions with atypia may pose significant diagnostic challenges. Given frequent increased proliferation rates in florid reactive urothelial atypia and limited studies on the interpretation of p53 stains in the urothelium (following current standard guidelines for correlation with P53 mutation status), we sought to further study the discriminatory value of Ki-67 and p53 for florid reactive urothelial atypia versus urothelial carcinoma in situ (CIS). Bladder specimens diagnosed as reactive urothelial atypia (n=40) and CIS (n=40) were assessed by immunohistochemical staining with antibodies for Ki-67, p53, CD44, and CK20. Immunoreactivity was scored based on percent cells positive for Ki-67 and pattern of reactivity with p53 (aberrant: diffuse strong positive or negative; normal: patchy/wild type). CD44 and CK20 reactivity patterns served as adjunctive internal validation controls for reactive urothelial atypia and CIS, as previously described. In reactive urothelial atypia, Ki-67 ranged from 0% to 90% (mean, 34%±26) with 30 cases (75%) having >10%. In CIS, Ki-67 ranged from 5% to 95% (mean, 50%±25) with 17 cases (43%) having >50%. In all 40 cases (100%) of reactive urothelial atypia, p53 expression had a wild-type pattern. In CIS, aberrant p53 expression was identified in 15 cases (37%): 3 cases (7%) were p53 negative (i.e. null phenotype) and 12 cases (30%) showed strong and diffuse nuclear reactivity (in >85% of cells). The remaining 25 cases (63%) of CIS had a p53 wild-type pattern of expression. Cytoplasmic CK20 immunoreactivity in umbrella cells was seen in 34 cases (85%) of reactive urothelial atypia, and 6 cases (15%) were negative. In addition, 35 cases (88%) of reactive urothelial atypia demonstrated full-thickness CD44 expression, while 5 cases (12%) had expression confined to the basal/parabasal layers of the urothelium. Strong and diffuse CK20 positivity was present in 39 cases (98%) of CIS, and patchy positivity was detected in 1 case (2%). None of the CIS cases overexpressed CD44: 16 cases (40%) showed focal expression in the nonneoplastic basal cell layer; 24 cases (60%) demonstrated no staining. In summary, Ki-67 has poor discriminatory value for reactive urothelial atypia versus CIS and adds little to the classic CK20/CD44 immunophenotype. While p53 sensitivity for CIS is relatively low (30%) and interpretation as either wild type or negative may be challenging in a small subset of cases, strong and diffuse nuclear reactivity was 100% specific in the distinction from florid reactive urothelial atypia in this cohort.

Cytokeratin 19 as a biomarker of highly invasive oral squamous cell carcinoma with metastatic potential

ObjectiveCytokeratin (CK) 19 is a member of the acidic type I CK family. Recently, CK19 expression has been found in various tumor tissues; however, the significance of this remains unknown. The purpose of this study is to clarify the roles of CK19 in the progression of oral squamous cell carcinoma (OSCC). MethodsA total of 100 patients who had been diagnosed with OSCC at our department between January 2011 and December 2016 was included. The patients were divided into three groups based on an optimal cut-off points (5% and 77%) of the labeling index (LI) as follows: group A; LI < 5%, group B; 5%≤ LI < 77%, group C; LI ≥ 77%. Then, clinicopathological features and survival rates were compared among the groups. ResultsHistologically high-grade tumors were significantly more common in group C than in groups A and B. Furthermore, the incidence of nodal metastasis was significantly higher in group C than in other groups. Intense CK19 immunoreactivity was detected in metastatic lymph nodes of groups B and C, but not from group A. Moreover, patients with advanced pN stage and extranodal extension were more common in groups B and C than group A. Disease-specific survival curves revealed poorer prognoses in group C. ConclusionsThese results suggest that CK19 is involved in OSCC invasion and metastasis and could be a novel biomarker of highly invasive OSCC with metastatic potential.

Abstract 4878: Prognostic significance of Arginase and CK19 expression in human hepatocellular carcinoma after surgical resection: Correlation with recurrence-free survival

Abstract Background. Arginase-1 is an enzyme that is responsible for the conversion of arginine to urea in the urea cycle. A previous study has shown prognostic value of arginase expression in HCC following surgical resection. However, clear distinction on the role of arginase-1 as a predictor of recurrence in hepatocellular carcinoma remains unanswered. Occasionally, CK19, a cholangiocytic marker can be expressed in HCC, but the combination of arginase-1 and CK19 expression has never been evaluated. In this study, we investigate the usefulness of arginase-1 and CK19 expression alone and in combination in the determination of tumor recurrence following surgical resection in patients with HCC. Design: Formalin-fixed paraffin embedded tissue sections from 112 HCCs were immunostained by an automated method (DAKO enVision + Dual Link System-HRP) using mouse monoclonal Arginase-1 (clone SL6ARG, Dako) and mouse monoclonal CK19 (clone RCK108, invitrogen). Nuclear and/or cytoplasmic reactivity was scored based on the intensity and percentage of positive cells in the tumor cells. Arginase-1 expression was separated into high (intense diffuse or regional positivity in &amp;gt; 50% of tumor cells) and low (weak or negative expression). The clinicopathologic variables including recurrence and survival were obtained from the patients charts and were correlated with the immunochemical results. Results: High arginase-1 expression was detected in 93 patients (83%), whereas CK19 was positive in 19 patients (17%). In the univariate analyses, CK19 positivity (+) in HCC was associated with decreased recurrence free survival when compared with CK19 negative HCC (P=0.001). Arginase-1 expression was not associated recurrence-free and overall survival. However, the combination of arginase-1 and CK19 is associated with decreased recurrence-free survival (p&amp;lt;0.001). Furthermore, Arginase-1/CK19+ combined with TNM staging (p=0.042), vascular invasion (p&amp;lt;0.001) multiple tumor numbers (p=0.02) may play a role as additional predictors of recurrence-free survival. In the multivariate analysis, TNM stage, vascular invasion and CK19 were identified as independent prognostic indicators for recurrence-free survival. In addition, vascular invasion was an independent prognostic predictor of overall survival. Conclusion: The combination of arginase-1 and CK19 immunoreactivity are potential biomarkers of adverse prognosis in HCC, correlating with presence of multiple tumors, vascular invasion and advanced stage. The results of this study may explain why clear beneficial effects of recombinant human arginase have not been demonstrated in clinical studies. Further study of arginase expression and its potential role as a therapeutic target in HCC appear warranted. Citation Format: Ifeyinwa E. Obiorah, Joeffery Chahine, Kyungmin Ko, ByoungUk Park, Jose deGuzman, Bhaskar Kallakury. Prognostic significance of Arginase and CK19 expression in human hepatocellular carcinoma after surgical resection: Correlation with recurrence-free survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4878.

Diagnostic accuracy of immunohistochemical markers in differentiation between basal cell carcinoma and trichoepithelioma in small biopsy specimens.

The distinction of trichoepithelioma from basal cell carcinoma in small superficial biopsies is important but often challenging. This has inspired many scientists to test the validity of immunohistochemical markers in the differential diagnosis. To develop an immunohistochemical protocol that helps in differentiation between both trichoepithelioma (TE) and basal cell carcinoma (BCC) with higher sensitivity and specificity. Using standard immunohistochemical techniques, we examined 10 TEs and 19 BCCs for the expression of CK19, Ki-67, androgen receptors (AR), CD10, and PHLDA1. Immunoreactivity of AR, Ki-67, and CD10 in tumor cells was significantly higher in BCC than TE with a diagnostic accuracy in BCC of 75.5%, 75.8%, and 79.3% respectively, whereas immunoreactivity of PHLDA1 in tumor cells and stromal CD10 was significantly higher in TE than BCC with a diagnostic accuracy in TE of 100% and 82.8%, respectively. In contrast, immunoreactivity for CK19 showed no statistically significant differences between both tumors. The analysis of CD10, Ki-67, and PHLDA1 can be used as a helpful immunohistochemical panel in the distinction between TE and BCC especially in small and superficial biopsies.

Validation of 34betaE12 immunoexpression in clear cell papillary renal cell carcinoma as a sensitive biomarker

Clear cell papillary renal cell carcinoma (CCPRCC) is a recently recognised neoplasm with a broad spectrum of morphological characteristics, thus representing a challenging differential diagnosis, especially with the low malignant potential multicystic renal cell neoplasms and clear cell renal cell carcinoma. We selected 14 cases of CCPRCC with a wide spectrum of morphological features diagnosed on morphology and CK7 immunoreactivity and analysed them using a panel of immunohistochemical markers, focusing on 34βE12 and related CKs 1,5,10 and 14 and several molecular analyses such as fluorescence in situ hybridisation (FISH), array comparative genomic hybridisation (aCGH), VHL methylation, VHL and TCEB1 sequencing and multiplex ligation-dependent probe amplification (MLPA). Twelve of 13 (92%) CCPRCC tumours were positive for 34βE12. One tumour without 3p alteration by FISH revealed VHL mutation and 3p deletion at aCGH; thus, it was re-classified as clear cell RCC. We concluded that: (1) immunohistochemical expression of CK7 is necessary for diagnostic purposes, but may not be sufficient to identify CCPRCC, while 34βE12, in part due to the presence of CK14 antigen expression, can be extremely useful for the recognition of this tumour; and (2) further molecular analysis of chromosome 3p should be considered to support of CCPRCC diagnosis, when FISH analysis does not evidence the common loss of chromosome 3p.

Retraction note: Metastatic ovarian papillary cystadenocarcinoma to the small intestine serous surface: report of a case of high-grade histopathologic malignancy.

Ovarian cystadenocarcinoma is characterized by marked heterogeneity and may be composed of an admixture of histologic growth patterns, including acinar, papillary and solid. In the present study, a case of isolated small intestine metastasis of ovarian papillary cystadenocarcinoma was reported. A 7-year-old female mixed-breed dog presented with a mass in the left upper quadrant with progressive enlargement of the abdomen, periodic bloody discharge from the vulva and incontinence. The tumor was histologically characterized by the presence of cysts and proliferation of papillae, both lined by single- or multi-layered pleomorphic epithelial cells. Furthermore, the mass was composed by intense cellular and nuclear pleomorphism and numerous mitotic figures. These findings indicate a tumor of high-grade malignancy with infiterative tumor cells resembling the papillary ovarian tumor in the serosal surface of the small intestine along with an intact serosa. Immunohistochemically, tumor was positive for CK7 and negative immunoreactivity for CK20. The histopathologic features coupled with the CK7 immunoreactivity led to a diagnosis of high grade ovarian papillary cystadenocarcinoma. To the best of our knowledge, this is the first case of small intestine serousal surface metastasis from ovarian papillary cystadenocarcinoma.

Epithelial and organ-related marker expression in pituitary adenomas.

The histologic expression of epithelial and organ-related immunohistochemical markers in primary sellar region tumors has received little attention to date. This lack of empirical data may lead to mistaken assumptions in the evaluation of sellar region neoplasms. To address this issue, the frequency and specificity of epithelial (cytokeratin 7(CK7), CK20) and organ-related differentiation markers (gross cystic disease fluid protein-15 (GCDFP-15), thyroid transcription factor-1 (TTF-1), Napsin A, paired box8 (PAX-8), hepatocyte paraffin 1 (HepPar1) and estrogen receptor (ER)) were studied in 40 patients with adenomas comprising five hormonal sub-types. Non-parametric statistical procedures were used to examine associations between marker expression and tumor sub-type. CK7 and CK20 immunoreactivity were seen in 48% and 8% of tumors, respectively, although never in a diffuse pattern. CK20 expression was nearly exclusive to corticotrophs, whereas CK7 frequently highlighted cells with dendritic-type morphology. The specificity of organ-related differentiation markers was 100% (monoclonal Napsin A, GCDFP-15 and TTF-1), 97% (HepPar1 and PAX-8), 90% (polyclonal Napsin A) and 72% (ER); no tumors demonstrated significant co-expression of these organ-related markers with either CK7 or CK20. The first major conclusion of this study is that CK7 staining in adenoma is more frequent than has been previously than has been previously described. CK7 immunoreactive cells often displayed a dendritic-type morphology, including within large macroadenomas, which raises the question as to whether these represent tumor cells with folliculo-stellate cell-type differentiation, as these also have dendritic cell-type morphology and express CK7 in non-neoplastic glands. The second major conclusion, which confirms earlier findings, is that CK20 staining is a very infrequent immunohistochemical finding in adenomas that is virtually limited to corticotrophs and thus is helpful in diagnostic confirmation of that sub-type. The final conclusion is in regard to those features that separate adenomas from sellar region metastases: adenomas do not demonstrate significant expression of TTF-1, monoclonal Napsin A, PAX-8, HepPar1 or GCDFP-15, nor do they exhibit diffuse expression of CK7 and CK20.

Follicular variant of papillary thyroid carcinoma (FVPTC): histological features, BRAF V600E mutation, and lymph node status.

Follicular variant of papillary thyroid carcinoma (FVPTC) is currently treated like conventional papillary thyroid carcinoma (cPTC). Recent reports indicate that encapsulated FVPTC behaves like follicular adenomas, while infiltrative FVPTC behaves like cPTC. This raises the possibility that histology and/or mutation status might help personalize management of FVPTC regarding extent of surgery, intensity of follow-up, and targeted therapy. This study correlates histological features, immunoreactivity for CK19, HBME, and Gal, and BRAF V600E mutation with lymph node (LN) metastasis and follow-up in FVPTC. Forty-eight FVPTC (21 with regional lymph node metastasis [LN+] and 27 with negative lymph nodes [LN-]) were reviewed. Demographics, tumor focality, size, circumscription, follicular architecture, lymphovascular invasion, extrathyroidal extension (ETE), and margin status were charted. Macrodissected formalin-fixed paraffin-embedded sections from 47 (21 LN+ and 26 LN-) cases were analyzed for BRAF V600E (1799T>A) mutation using real-time PCR. Correlations between the variables and LN status were calculated. Sixty-two percent of cases with ETE demonstrated LN metastasis, while 59 % of cases with circumscribed tumors were LN-. In multivariable analysis, ETE and tumor size ≥1 cm were the best predictors of LN+ status, whereas in cases without ETE, the infiltrative pattern and tumor size provided the "best fit." Immunostains and BRAF mutation status were not helpful. All four tumors that recurred were LN+, with infiltrative borders, and lacked the BRAF mutation. Tumor circumscription, extrathyroidal extension, and tumor size ≥ 1.0 cm are predictors of lymph node status in FVPTC.

Culture and Characterization of Oral Mucosal Epithelial Cells on a Fibrin Gel for Ocular Surface Reconstruction

Aim of the study: To develop a clinical grade fibrin gel for the culture of oral mucosal epithelial cells (OMEC) intended for ocular surface reconstruction in the treatment of limbal stem cell deficiency (LSCD).Materials and methods: Transparent fibrin gels composed of fibrinogen and thrombin were developed for the culture of epithelial cells. Oral mucosa was harvested from the buccal region of healthy volunteers and cultured as explants on fibrin gels. Tranexamic acid (TA), a clinically approved anti-fibrinolytic agent was added to prevent the fibrin gel from digesting due to cellular activity. The gels were stained for p63α (as a marker of poorly differentiated epithelial cells), CK19, CK13 and CK3 (expressed by OMEC). Epithelial cell stratification was observed using hematoxylin–eosin staining.Results: Addition of TA prevented gels from dissolving during the culture period. OMEC proliferated on the fibrin gel and attained confluence over a 2-week period (±2 d) and exhibited a typical epithelial, cobblestone morphology. Basal OMEC exhibited positive staining for p63α while the superficial cells exhibited positive staining for CK3. The cells expressed a strong immunoreactivity for CK19 and CK13 suggesting that they retained a normal oral epithelial phenotype.Conclusion: Fibrin gels, maintained in the presence of TA, to control the rate of substrate degradation, provide a more robust yet transparent substrate for the culture and transplantation of cultured OMEC. The fibrin gels are easily standardized, the components commercially available, and produced from clinically approved materials. The resulting stratified OMEC-derived epithelium displays characteristics similar to that of a human cornea, e.g. CK3 expression. The conventional dependence on a murine feeder layer for support of epithelial cells is unnecessary with this technique and hence, provides for an attractive alternative for treatment of LSCD.

Diagnostic utility of TP53 and cytokeratin 7 immunohistochemistry in idiopathic inflammatory bowel disease-associated neoplasia

Long-standing inflammatory bowel disease is associated with increased risk of developing colorectal adenocarcinoma. Significant intra- and inter-observers' variability exists in histologic interpretation of dysplasia in surveillance biopsies. In this study, we evaluated the utility of a panel of immunohistochemical markers in diagnosing inflammatory bowel disease-associated neoplasia. We reviewed 39 colectomy specimens with inflammatory bowel disease-associated neoplasia. In these 39 cases, we identified 172 foci of interest (5 normal, 58 negative for dysplasia, 15 indefinite for dysplasia, 59 low-grade dysplasia, 18 high-grade dysplasia, and 17 invasive adenocarcinoma). They were subjected to immunohistochemistry for TP53 and CK7. Logistic regression was used to evaluate their association with the presence of dysplasia. Receiver operating characteristic curves were used to determine the optimal cutoffs and assess the diagnostic performance of TP53 and CK7. Both TP53 nuclear staining and CK7 immunoreactivity gradually increased in the progression of inflammatory bowel disease-associated neoplasia (P<0.0001). CK7 immunoreactivity increased along with the increase of inflammation severity (P=0.0002) as well as reactive changes (P=0.04) in the colonic mucosa. But TP53 nuclear staining was independent of either feature. When both TP53>8% and CK7>30% as identified from logistic regression and receiver operating characteristic curves were used to diagnose dysplasia, the specificity achieved as high as 95%. When either TP53>8% or CK7>30% was used to diagnose dysplasia, the sensitivity achieved was 82%. Our results suggested that a combination of CK7 and TP53 immunohistochemistry may be helpful in diagnosing inflammatory bowel disease-associated dysplasia in difficult cases.

Multifocal Large Cystic Liver Metastasis of a Sinonasal Tract Ameloblastoma: An Unusual Clinical Presentation

Ameloblastoma is a slowly growing, locally invasive tumor of odontogenic epithelial origin. On rare occasion, a well-differentiated ameloblastoma may metastasize. Recently, we encountered a unique case of metastatic ameloblastoma in the liver in a 48-year-old woman. Preoperative radiographic study revealed multiple cystic lesions in the liver, 6 of which were confirmed intraoperatively. Macroscopic examination of the resected tumors revealed well-circumscribed, encapsulated cystic lesions. Sections from the tumors demonstrated solid interlocking islands with peripheral palisading of “basaloid cells” and squamous differentiation of centrally located cells. The cytology of these tumors was bland and the mitotic activity was low. Immunohistochemistry showed immunoreactivity for CK5/6 and p63, immunoreactivity for CD10 in the peripherally palisading cells and immunoreactivity for CK19 in the centrally located cells. The resected liver cystic tumors were originally diagnosed as “low-grade cystic ameloblastoma-like tumor in the liver” and suggested a possibility of metastasis. The patient was doing well clinically after the resection of her liver lesions. However, CT scan of the head and neck region at another hospital one year later showed an enhancing, expansile, well circumscribed mass in the right nasal cavity. Biopsy and resection of the nasal mass revealed an ameloblastoma invading the maxillary bone. The patient is doing well 2 months after her nasal surgery. To our knowledge, this is the first case of ameloblastoma manifested as liver metastases prior to the identification of a sinonasal primary. J Med Cases. 2013;4(8):544-549 doi: https://doi.org/10.4021/jmc1314w

Multifocal Large Cystic Liver Metastasis of a Sinonasal Tract Ameloblastoma: An Unusual Clinical Presentation

Ameloblastoma is a slowly growing, locally invasive tumor of odontogenic epithelial origin. On rare occasion, a well-differentiated ameloblastoma may metastasize. Recently, we encountered a unique case of metastatic ameloblastoma in the liver in a 48-year-old woman. Preoperative radiographic study revealed multiple cystic lesions in the liver, 6 of which were confirmed intraoperatively. Macroscopic examination of the resected tumors revealed well-circumscribed, encapsulated cystic lesions. Sections from the tumors demonstrated solid interlocking islands with peripheral palisading of “basaloid cells” and squamous differentiation of centrally located cells. The cytology of these tumors was bland and the mitotic activity was low. Immunohistochemistry showed immunoreactivity for CK5/6 and p63, immunoreactivity for CD10 in the peripherally palisading cells and immunoreactivity for CK19 in the centrally located cells. The resected liver cystic tumors were originally diagnosed as “low-grade cystic ameloblastoma-like tumor in the liver” and suggested a possibility of metastasis. The patient was doing well clinically after the resection of her liver lesions. However, CT scan of the head and neck region at another hospital one year later showed an enhancing, expansile, well circumscribed mass in the right nasal cavity. Biopsy and resection of the nasal mass revealed an ameloblastoma invading the maxillary bone. The patient is doing well 2 months after her nasal surgery. To our knowledge, this is the first case of ameloblastoma manifested as liver metastases prior to the identification of a sinonasal primary. J Med Cases. 2013;4(8):544-549 doi: https://doi.org/10.4021/jmc1314w

Metastatic clear cell papillary renal cell carcinoma: first case report of a previously indolent entity

Aims Clear cell papillary renal cell carcinoma is a recently characterised low grade neoplasm which has not yet been documented to have metastasised. We report a case of clear cell papillary renal cell carcinoma with histologically proven lymph node metastasis. Method H&E sections were reviewed by two experienced uro-pathologists. Immunostaining of both the primary tumour and the lymph node metastases was performed. Results Examination of the radical nephrectomy specimen showed an 85 mm cystic tumour which was grossly organ con-fined. Histologically the tumour was characterised by areas of well developed delicate papillary structures lined by clear cells with reverse polarisation and low-grade nuclear features. Areas of nested and tubular architecture were also present. The tumour invaded into hilar fat although vascular invasion was not identified. The tumour exhibited patchy although strong CK7 immunoreactivity. Metastatic renal cell carcinoma with similar histological features was identified in two paracaval lymph nodes. Discussion We present a case of metastatic clear cell papillary renal cell carcinoma, which is, to our knowledge, the first that has been described.

The application of immunocytochemistry to cytologic direct smears of metastatic merkel cell carcinoma

Merkel cell carcinoma represents a highly aggressive cutaneous malignancy characterized by regional recurrences, lymph node metastases, distant metastases, and high mortality. As the cytomorphology of Merkel cell carcinoma can be mimicked by other malignancies, especially lymphoma and pulmonary small cell carcinoma, immunocytochemistry is often useful in confirming the diagnosis. Cell blocks, which are traditionally utilized for immunocytochemistry, occasionally exhibit insufficient cellularity. Hence, we prospectively investigated the application of CK20 immunocytochemistry to air-dried, unstained direct smears in the diagnosis of Merkel cell carcinoma fine needle aspirates (FNAs). Eight consecutive FNAs of Merkel cell carcinoma were prospectively examined in this series; seven (88%) cases exhibited immunoreactivity for CK20 in the tumor cells. The one CK20-negative Merkel cell carcinoma was immunoreactive for synaptophysin and CD56. This immunophenotype was identical to that of the original primary tumor. For comparison, air-dried direct smears prepared from three pulmonary small cell carcinoma FNAs were examined by CK20 immunocytochemistry. In all cases, no CK20 immunoreactivity was seen in any of the tumor cells. In conclusion, direct smears represent a feasible and robust source of cellular material for immunocytochemical studies to diagnose Merkel cell carcinoma. This methodology allows the cytologist to confirm on site that material for diagnostic immunocytochemistry is present thereby serving as a safeguard in instances where insufficient cell block cellularity is anticipated or encountered.

A Histologic and Immunohistochemical Study Describing the Diversity of Tumors Classified as Sinonasal High-grade Nonintestinal Adenocarcinomas

Nonintestinal sinonasal adenocarcinomas (SNACs) are somewhat poorly characterized and high-grade nonintestinal SNACs have been only rarely reported. Here, we review our experience with these tumors. Twenty-seven cases of high-grade nonintestinal SNACs were identified from 22 men and 5 women. Ages ranged from 22 to 83 years (mean±1 standard deviation=54.7±18.6 y; median=60 y). Thirteen cases involved the nasal cavity and sinuses, 10 involved the nasal cavity only, and 4 involved sinuses only. Most cases had marked cytologic and nuclear pleomorphism, abundant mitotic activity, and necrosis; however, these features were not uniform. Although histologically heterogeneous, recurrent growth patterns were seen that resembled other neoplasms of the area. Tumors lacked CDX2 and CK20 immunoreactivity (aside from rare CK20 immunoreactive cells). High-grade nonintestinal SNACs are more common in men and, although they occur over a wide age range, they are much more common in older individuals. Histologically, they show a great deal of heterogeneity.

Cytokeratin 18 is a specific marker of bovine intestinal M cell

Microfold (M) cells in the follicle-associated epithelium (FAE) of Peyer's patches have an important role in mucosal immune responses. A primary difficulty for investigations of bovine M cells is the lack of a specific molecular marker. To identify such a marker, we investigated the expression of several kinds of intermediate filament proteins using calf Peyer's patches. The expression patterns of cytokeratin (CK) 18 in jejunal and ileal FAE were very similar to the localization pattern of M cells recognized by scanning electron microscopy. Mirror sections revealed that jejunal CK18-positive cells had irregular and sparse microvilli, as well as pocket-like structures containing lymphocytes, typical morphological characteristic of M cells. However, CK18-negative cells had regular and dense microvilli on their surface, typical of the morphology of enterocytes. In contrast, CK20 immunoreactivity was detected in almost all villous epithelial cells and CK18-negative cells in the FAE. CK18-positive proliferating transit-amplifying cells in the crypt exchanged CK18 for CK20 above the mouth of the crypt and after moving to the villi; however, CK18-positive M cells in the crypt continued their expression of CK18 during movement to the FAE region. Terminal deoxynucleotidyl-transferase-mediated deoxyuridine-triphosphate-biotin nick-end labeling-positive apoptotic cells were specifically detected at the apical region of villi and FAE in the jejunum and ileum, and all were also stained for CK20. These data indicate that CK18 may be a molecular marker for bovine M cells in FAE and that M cells may transdifferentiate to CK20-positive enterocytes and die by apoptosis in the apex of the FAE.