Parathyroid Hormone-Related Protein-Producing Adenocarcinoma Suspicious of Lung Cancer: A Case Report.

Introduction: Lung adenocarcinoma with parathyroid hormone (PTH)-related hypercalcemia is uncommon. Case Presentation: A 69-year-old man was admitted to our hospital due to anorexia and fatigue. Serum calcium (15.0 mg/dL) and carcinoembryonic antigen (361.7 ng/mL) were extremely high, and PTH-related protein (PTH-rP) also elevated (16.7 pmol/L). Systemic computed tomography revealed multiple enlarged lymph nodes and disseminated peritoneal nodules, with irregularly shaped nodules in the upper lobe in the left lung. Ultrasound-guided biopsy from the axillary lymph node revealed adenocarcinoma. Immunohistological staining showed the tumor cells to be positive for cytokeratin 7 and PTH-rP and negative for cytokeratin 20 and thyroid transcription factor-1. Although the primary origin remains undetermined despite detailed examinations, possible primary tumor was considered to be lung adenocarcinoma in the present case. The serum calcium level was reduced by denosumab, but the patient died 20 days after admission. Conclusion: The present case demonstrated the importance of considering oncological emergency, such as hypercalcemia and/or PTH-rP-producing hypercalcemia, in patients with adenocarcinoma.

Clinical significances of TTF-1, neuroendocrine (chromogranin, synaptophysin, CD56), and keratin (pancytokeratin, CK7, CK5/6) marker immunostaining in small cell lung cancer.

PURPOSE: Immunohistochemistry (IHC) markers have established a role in the pathological diagnosis of small cell lung cancer (SCLC) and especially neuroendocrine markers help to differentiate SCLC from other tumors. The study aimed to evaluate the clinical role of different IHC markers in SCLC patients. METHODS: A total of 378 SCLC patients were enrolled in the study and analyzed retrospectively. TTF-1, neuroendocrine markers (chromogranin, synaptophysin, and CD56), and keratin markers (pancytokeratin, CK7 and CK5/6) were assessed. RESULTS: CD56 had the highest expression (92.3%) followed by pancytokeratin (82.8%), TTF-1 (74.8%), synaptophysin (72.7%), chromogranin (55.6%), CK7 (54.8%), and CK5/6 (9%). No differences were observed in the expression of all markers according to the stage of the disease. Extended disease SCLC (ED-SCLC) patients with synaptophysin expression had a higher response to chemotherapy compared to those without staining (p = 0.01); on the other hand, the chemotherapy response of these patients was not significantly different when they expressed CK7 (p = 0.06). Pancytokeratin expression was associated with favorable survival in both limited disease SCLC (LD-SCLC) (p = 0.02) and ED-SCLC (p = 0.005) patients. Similarly, ED-SCLC patients with CD56 staining lived longer than those without expression (p = 0.001). The lack of synaptophysin expression in LD-SCLC patients (p = 0.06) and TTF-1 expression in ED-SCLC patients (p = 0.06) were correlated with better survival rates. CONCLUSION: We conclude that IHC markers, used frequently in the diagnosis of SCLC, might also be used in clinical decision-making, since they are correlated with predictive and prognostic factors for the disease.

Expression of cytokeratin 7/20 and Ki67 in Helicobacter pylori-associated gastritis and intestinal metaplasia.

INTRODUCTION: Cytokeratins (CKs) have been associated with precancerous and cancerous gastric lesions in patients with Helicobacter pylori-associated chronic gastritis, making them useful for diagnosing epithelial tumors. METHODOLOGY: A retrospective study was conducted utilizing 200 formalin-fixed paraffin-embedded gastric biopsy samples collected from the lesser curvature of the stomach. Samples from the control group, patients with H. pylori infection, and patients with H. pylori-associated gastritis, with complete and incomplete intestinal metaplasia (IM) were immunostained. Monoclonal antibodies were utilized to determine the expression of CK7, CK20, and Ki-67. RESULTS: Patients infected with H. pylori had strong CK20 expression on the surface, and weak CK7 expression on the surface and deep glands; while non-specific chronic gastritis patients had weak focal CK7 expression and strong CK20 expression. The normal gastric mucosa of patients in the control group had relatively weak CK7 expression, restricted to a few cells in the neck and deep glands. CK20 showed diffuse strong reactivity on the surface. On the other hand, patients with complete IM showed a CK7 staining pattern that was either negative or weakly focal on the surface and crypts associated with diffuse surface CK20 and focal crypt staining corresponding to gastric type IM. The Ki67 proliferating index was low (≤ 15%) in H. pylori infected patients, high (> 30%) in patients with incomplete IM, and intermediate (16-30%) in patients with complete IM. CONCLUSIONS: These results indicate a significant link between the expressions of CK7/CK20 and Ki67 in patients afflicted with H. pylori and IM.

Canine ovarian epithelial tumours: histopathological and immunohistochemical evaluation with proposed histopathological classification system.

Canine ovarian epithelial tumours (OETs) are currently divided into ovarian adenomas and carcinomas, which are further inconsistently subclassified as papillary or cystic, whereas in human medicine, OETs are subdivided into several subtypes. This study aimed to establish clear morphological features enabling more consistent distinction between benign OETs and ovarian carcinomas (OvCas) as well as defining different histopathological patterns of canine OvCas. Analysis revealed a mitotic count threshold of >2 as a potential criterion for differentiating OvCas from benign OETs. Alongside ovarian adenomas, ovarian borderline tumours were introduced as a distinct category among benign OETs. OvCas exhibited five different histopathological patterns, namely papillary, solid with tubular differentiation, micropapillary, cystic and sarcomatous. Since some OvCas can morphologically overlap with other ovarian tumours, the expression of cytokeratin 7, a cytokeratin expressed in ovarian epithelium, was assessed and proved helpful, although it was not expressed in all cases. Furthermore, we investigated the expression of 14-3-3σ and cyclooxygenase 2 (COX-2). Based on the frequent expression of 14-3-3σ, this marker appears to have a role in canine OETs since it is not expressed in normal canine ovaries. The infrequent expression of COX-2 suggests that it is a poor candidate as a potential therapeutic target in canine OvCas.

Canaliculocoele: A Case Series and Review of Literature.

AIM: To report a case series on canaliculocoele and to review the existing literature. METHODS AND MATERIALS: A retrospective analysis of the case records of all patients diagnosed with canaliculocoele between January 1st, 2018, and December 31st, 2019, was conducted. Only histopathologically proven cases of canaliculocoele with a minimum follow-up of 6 weeks were included. RESULTS: Five cases of canaliculocoele that presented over 2 years were included. The mean age was 58.8 ± 9.63 years, with a female preponderance. The mean duration of symptoms was 22.2 ± 22.71 months. All patients had medial cystic swelling, either at the upper or lower lid. Four patients had gross stenosis of the punctum, while the punctum was absent in one patient. Ultrasound biomicroscopy showed canalicular cystic distension with intra-lesional hyper-reflective echoes. All patients were managed with a complete cystectomy, except for one where a marsupialization was done. Adjunctive mini-Monoka intubation was done in two patients. The histopathological diagnosis of all cases was consistent with canaliculocoele. The mean follow-up was 3.82 ± 2.77 months. CONCLUSION: Canaliculocoele is mostly unilateral and seen in middle-aged women. A good clinical evaluation supported by diagnostic imaging along with an affirmative histopathology can confirm the diagnosis.

FOXA1/CK7-positive Esophageal Squamous Cell Carcinoma with Aggressive Liver Metastasis: A Case Report.

Cytokeratin (CK) is a specific marker of adenocarcinoma. However, cases of CK7-positive esophageal squamous cell carcinoma (ESCC) have only rarely been reported. We herein report a case of unresectable CK7-positive ESCC with aggressive liver metastasis following nivolumab treatment initiation. Nivolumab treatment was discontinued after one course because of complications. Notably, the liver metastases exhibited accelerated growth. Immunostaining of the necropsy specimens revealed diffuse positivity for forkhead box protein A1 (FOXA1)/CK7, thus indicating a potent poor immune response. The potential correlation between CK7 expression and the immune checkpoint inhibitor response may offer valuable insights into the development of effective therapeutic strategies.

A young female patient with multiple unilateral low-grade oncocytic renal tumors and angiomyolipoma: a case report and literature review.

We identified a young female patient admitted for suspected renal malignancy. Partial nephrectomy was performed after imaging evaluation and discussion. Postoperative biopsy pathology reported multiple low-grade eosinophilic renal tumors (LOTs) with angiomyolipoma growth. After reviewing the data, we found that LOT was mostly solitary and occurred in middle-aged and elderly patients. This case is unique and we share it to improve the understanding of this disease.

Analysis of clinicopathologic and imaging features of dual-phenotype hepatocellular carcinoma.

Dual-phenotype hepatocellular carcinoma (DPHCC) is a new subtype of hepatocellular carcinoma (HCC). This study aimed to investigate the relationship between the computerized tomography scan (CT) imaging and clinicopathologic features of DPHCC. The CT imaging and clinicopathologic data of 97 HCC cases who underwent radical resection were collected retrospectively. The CT imaging feature was evaluated by the ratio of the average CT value of tumor to liver (TLR) in the plain scan, arterial, portal vein and delayed phases. The association between CT imaging and clinicopathologic features was analyzed using the t-test or chi-square test. Univariate and multivariate recurrence-free survival (RFS) analysis and overall survival (OS) were performed. The positive rates of cytokeratin 7 (CK7) and CK19 were 35.1% and 20.6% respectively. The positive rate of CK19 was significantly higher in cases with age < 47 years (P = 0.005), tumor diameter > 4 cm (P = 0.016) or AFP ≥ 400 ng/ml (P = 0.007). The TLR in the portal vein phase was significantly lower in CK19 positive group (P = 0.024). The recurrence risk was significantly higher in cases with CK19 positive (HR: 2.17, 95% CI 1.16 to 4.04, P = 0.013), tumor diameter > 4 cm (HR: 2.05, 95% CI 1.11 to 3.78, P = 0.019), AFP ≥ 400 ng/ml (HR: 2.50, 95% CI 1.37 to 4.54, P = 0.002) or CA199 ≥ 37 U/ml (HR: 2.23, 95% CI 1.12 to 4.42, P = 0.020). However, imaging features, pathological subtype, CK7 or CK19 expression were not significantly related to HCC OS in the univariate and multivariate analysis (all P > 0.05). The expression of CK19 may be associated with the enhancement feature of the portal vein phase CT image, and CK19 positive may suggest a worse RFS.

Immunohistopathological Study of Papillary Squamotransitional Carcinoma of Uterine Cervix.

INTRODUCTION: Papillary squamotransitional cell carcinoma (PSTCC) arising from the uterine cervix is a distinctive histomorphological subtype of squamous cell carcinoma (SCC) not otherwise specified (NOS) of cervical epithelial tumors. AIM: The present study was undertaken to study the histopathological features and immunoexpression of CK7, CK20, p53 and Ki-67 in PSTCC of the cervix. MATERIALS AND METHODS: This study included 43 cases of PSTCC of cervix. A technique of manual tissue array was employed along with IHC staining of entire section in some cases. The expression pattern of CK7, CK 20, p53 and Ki67 in PSTCC was studied and clinico-pathological correlation of various parameters with IHC expression of CK7 and CK20 was observed. Results were subjected to statistical analysis and were considered significant when the p-value was less than 0.05. RESULTS: Out of 43 PSTCC cases, there were 38 squamotransitional type and 5 papillary type. Histomorphologically, all the cases studied were having fused papillae with rounded contours and fibrovascular cores with highest number of cases having intermediate cell type morphology (86%). Stromal invasion was seen in 74.4% of cases. Koilocytosis were seen in 39.3% of cases. Thirty-two cases showed CK7 immunopositivity (+) and CK20 immunonegativity (-), nine cases were both CK7 and CK20 - and two cases were CK7- and CK20+. Among them 90.7% cases were p53 positive and all cases were positive for Ki67 immunostaining with highest number of cases showing moderate proliferative activity (74.4%); followed by nine cases showing high (20.93%) and two cases showing low proliferative activity (4.65%). CONCLUSION: The distinct histomorphology and CK7/CK20 immnunoprofile of PSTCC along with Ki67 and p53 could help in arriving at an accurate diagnosis as well predicting its biological behavior.

Clinical impact of ampulla of Vater cancer subtype classification based on immunohistochemical staining.

BACKGROUND: The histological subtype is an important prognostic factor for ampulla of Vater (AoV) cancer. This study proposes a classification system for the histological subtyping of AoV cancer based on immunohistochemical (IHC) staining and its prognostic significance. METHODS: Seventy-five AoV cancers were analyzed for cytokeratin 7 (CK7), CK20, and causal-type homeobox transcription factor 2 (CDX2) expression by IHC staining. We differentiated the subtypes (INT, intestinal; PB, pancreatobiliary; MIX, mixed; NOS, not otherwise specified) into classification I: CK7/CK20, classification II: CK7/CK20 or CDX2, classification III: CK7/CDX2 and examined their associations with clinicopathological factors. RESULTS: Classifications I, II, and III subtypes were INT (7, 10, and 10 cases), PB (43, 37, and 38 cases), MIX (13, 19, and 18 cases), and NOS (12, 9, and 9 cases). Significant differences in disease-free survival among the subtypes were observed in classifications II and III using CDX2; the PB and NOS subtype exhibited shorter survival time compared with INT subtype. In classification III, an association was revealed between advanced T/N stage, poor differentiation, lymphovascular invasion (LVI), the PB and NOS subtypes, and recurrence risk. In classification III, the subtypes differed significantly in T/N stage and LVI. Patients with the PB subtype had advanced T and N stages and a higher incidence of LVI. CONCLUSIONS: Classification using CDX2 revealed subtypes with distinct prognostic significance. Combining CK7 and CDX2 or adding CDX2 to CK7/CK20 is useful for distinguishing subtypes, predicting disease outcomes, and impacting the clinical management of patients with AoV cancer.

Superior Vesical Fissure as an Incomplete Form of Bladder Exstrophy: A Case Report with Clinico-Pathological Correlation and a Comprehensive Literature Review.

Multiple variants of classic bladder exstrophy have been described, all of them infrequent. Superior vesical fissure is a mild variant of this pathology in which genital involvement is scarce or absent. To date, there are only isolated reports of this entity. We report a full-term female patient of Arabian descent with a clinical and radiological diagnosis of superior vesical fissure that was surgically corrected in our center with a favorable evolution. Histological study, supported by immunohistochemical techniques, showed squamous and transitional epithelium and discrete chronic inflammation. Our literature review identified 26 reports of superior vesical fissure (including ours), with high heterogeneity in terms of clinical characterization and associated malformations and with only two histological reports. The clinical evolution of the patients reported in the literature was favorable, with lower morbidity and mortality than in classical forms of bladder exstrophy.

Evaluation of Cytokeratin-7 and Cytokeratin-19 Expression Relationship with Gleason Score in Prostatic Adenocarcinoma.

Background & Objective: Prostatic adenocarcinoma (PAC) is one of the most common tumors worldwide. Immunohistochemical expression of cytokeratins has been evaluated in the diagnosis and prognosis of tumors. The aim of the present study is the evaluation of Cytokeratin-7 (Ck-7) and Cytokeratin-19 (Ck-19) expression and its relationship with Gleason score in patients with PAC. Methods: In this cross-sectional study, 78 samples from 78 patients with PAC referred to Mostafa Khomeini Hospital were gathered. Samples were immunohistochemically stained by Ck-7 and Ck-19 markers. The percentage of each marker in tumor cells was determined, and its relationship with Gleason scores and Gleason grade groups was analysed by SPSS version 24. Results: The expression of Ck-7 and Ck-19 were seen in 37.2% and 82.1% of samples, respectively. The mean of Ck-7 expression in tumor cells was 4.98%±7.19 (ranged 0 to 26%), while the mean of Ck-19 expression was 41.02%±23.36 (ranged 0 to 78%). There was no relationship between Ck-7 expression with Gleason scores and Gleason grade groups. However, Ck-19 expression was increased in higher Gleason scores and Gleason grade groups (P<0.001). No relationship was found between age and Ck-7 (P=0.309) and Ck-19 (P=0.375). Conclusion: The Ck-7 expression in PAC samples is weak and focal and had no relationship with the Gleason scores and Gleason grade groups. However, Ck-19 expression in PAC was high and was associated with tumor dedifferentiation of samples. There was no relationship between the expression of both markers with the patient's age.

Metastatic hepatocellular carcinoma of the oral cavity - A report of two cases.

Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide that is etiologically linked to a previous hepatitis B infection. We describe two cases of HCC metastasis to the oral cavity in 60- and 67-year-old male patients. The first case was a diffuse, hard swelling in the left body of the mandible. Histopathologic and immunohistochemical analysis was done, and a positive for CK7, CK19, HEPPAR and TTF and a negative for NAPSIN were found to be diagnostic of metastatic HCC. Subsequent examination of the serum alfa- fetoprotein (AFP) level showed a high value of 450 ng/ml, confirmatory of HCC. The second case was a pedunculated, reddish, mobile soft tissue growth on the retromolar region. Its macroscopic and histopathologic features themselves were confirmatory of HCC, and the elicited history was corroborant of metastasis.

Intracranial tumor-to-tumor metastasis in an elderly female: An unusual case report.

Tumor-to-tumor metastasis is an extremely rare event, with only 150 reported cases in the literature. Meningioma, renal carcinoma, and tumors of the thyroid are the commonest sites of metastasis. Lung, breast, and GI-tract cancers are the most common types that undergo metastasis. Meningioma is the most common intracranial tumor as recipient of the tumor-to-tumor metastasis. Although breast carcinoma is the most common tumor to metastasize, adenocarcinoma from other organs can also spread to meningiomas, like the ovary and upper gastrointestinal (GI). We report a case of adenocarcinoma metastasis to meningioma with the possibility of primary involvement of the ovary or upper GI. A 77-year-old female patient presented to neurosurgery with episodes of multiple seizures and loss of consciousness. An MRI suggested a left frontotemporal meningioma. The patient underwent craniotomy with mass dissection. Microscopic examinations showed a dual tumor containing both components of meningioma with a metastatic adenocarcinomatous component. The tumor cells were positive for cytokeratin (CK7). Thus, the final diagnosis was made as meningothelial meningiomas (WHO grade I) with metastatic mucinous adenocarcinoma, possible primaries of the ovary or upper GI tract. The patient could not be followed up as we lost the patient a few days after surgery.

Development and validation of a decision tree for distinguishing pulmonary adenocarcinomas with mucinous features and metastatic colorectal adenocarcinoma.

BACKGROUND: Diagnosis of mucinous carcinomas in the lung on transbronchial biopsy or fine-needle aspiration (FNA) samples can be difficult for the pathologist, because primary and metastatic tumors can have similar morphological, immunohistochemical, and molecular characteristics. Correct diagnosis is key to determine appropriate therapy and to distinguish primary from metastatic disease. This distinction often falls to the pathologist in patients with a history of mucinous adenocarcinoma of the colon. Despite its drawbacks, immunohistochemistry is often employed to help assign a primary site for mucinous adenocarcinomas in the lung. However, the published data in this regard is limited to studies that use only a handful of markers. METHODS: The authors examined the staining characteristics and heterogeneity of CK7, TTF-1, NapsinA, CK20, CDX2, and SATB2 in resection specimens of pulmonary adenocarcinomas with mucinous features and metastatic colorectal adenocarcinoma. RESULTS: Based on the heterogeneity, sensitivity, and specificity in this cohort, the authors developed a decision tree based on TTF-1, SATB2, CDX2, and CK7 to categorize tumors as primary or metastatic lesions. Validation of the decision tree in FNA specimens from the lungs and lung-draining lymph nodes showed 84% concurrence in cases from the lung and 100% concurrence in cases from the lymph node. In cases where the algorithm assigned a primary site, it was 95% accurate compared to the multidisciplinary diagnosis. CONCLUSIONS: This method holds promise in distinguishing primary versus metastatic lesions in resection, biopsy, and FNA samples from the lungs.

Diagnostic performance of transient elastography in differentiation between porto-sinusoidal vascular liver disease and compensated cirrhosis.

BACKGROUND AND AIMS: The efficacy of transient elastography (TE) in the differential diagnosis between porto-sinusoidal vascular disease (PSVD) and compensated cirrhosis has not been sufficiently studied. We aimed to investigate the diagnostic performance of TE and identify histological lesions associated with liver stiffness. METHODS: We conducted a retrospective cohort study including patients with PSVD and cirrhosis (Child-Turcotte-Pugh class A) and healthy subjects. Both the PSVD and cirrhotic patients had at least one sign of PH. The area under the receiver operating characteristic curve (AUROC) was used for differentiation. RESULTS: Ninety-two patients with PSVD (median age: 53 years, 33% male), 100 patients with compensated cirrhosis and 101 healthy subjects were included. The median TE-LSM in the PSVD patients (10.0 [7.0-13.0] kPa) was significantly lower than that in the cirrhotic patients (21.0 [15.0-28.0] kPa, p < .001) but was significantly higher than that in the healthy subjects (5.1 [4.6-6.0] kPa, p < .001). The AUROCs of TE-LSM for the discrimination of PSVD from the cirrhosis and healthy subjects were 0.886 (95% CI: 0.833-0.928) and 0.913 (95% CI: 0.864-0.949), respectively. The sensitivity and specificity to discriminate PSVD from compensated cirrhosis were 78.3% and 82.0%, respectively, at a cut-off of 13.6 kPa. Furthermore, portal fibrosis and aberrant cytokeratin 7 expression of centrilobular hepatocytes were significantly associated with higher TE-LSM (≥10.0 kPa). CONCLUSION: TE-LSM can be used to differentiate PSVD from compensated cirrhosis. Pathological features in association with increased liver stiffness are identified.

Ampullary Cancer: Histological Subtypes, Markers, and Clinical Behaviour-State of the Art and Perspectives.

There are different cancers in the peri-ampullary region, including pancreatic ductal adenocarcinoma (PDAC), duodenum cancers (DCs), and ampullary adenocarcinoma (AAC). Here, significant morphological-molecular characterizations should be necessary for the distinction of primary tumours and classifications of their subtypes of cancers. The sub classification of AACs might include up to five different variants, according to different points of view, concerning the prevalence of the two more-cellular components found in the ampulla. In particular, regarding the AACs, the most important subtypes are represented by the intestinal (INT) and the pancreato-biliary (PB) ones. The subtyping of AACs is essential for diagnosis, and their identifications have been impacting clinical management responses to treatments and overall survival (os) after surgery. Pb is associated with a worse clinical outcome. Otherwise, the criteria, through which are possible to attribute its subtype classification, are not well established. A triage of immune markers represented by CK7, CK20, and CDX-2 seem to represent the best compromise in order to split the cohort of AAC patients in the INT and PB groups. The test of choice for the sub-classification of AACs is represented by the immuno-histochemical approach, in which its molecular classification acquires its diagnostic, predictive, and prognostic value for both the INT and PB patients.

CK-7 negative primary lung adenocarcinoma.

Cytokeratin (CK) 7 is normally expressed in the vast majority of lung adenocarcinoma (ADC). However, on rare occasions, as reported in this paper, CK7 negativity can challenge the diagnosis of pulmonary ADC. Hence, the need to use a combination of 'immunomarkers' such as thyroid transcription factor 1, Napsin A, p40, p63 and CK20.

The Role of Immunohistochemistry in the Differential Diagnosis between Intrahepatic Cholangiocarcinoma, Hepatocellular Carcinoma and Liver Metastasis, as Well as Its Prognostic Value.

Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary hepatic malignant tumor, after hepatocellular carcinoma (HCC). Its incidence has risen worldwide, yet the only potentially curative treatment, surgical resection, is seldom applicable, and the median overall survival remains extremely low. So far, there are no personalized therapy regimens. This study investigated whether routine immunohistochemical stains have diagnostic and/or prognostic value in iCCA. Clinical, imaging, and pathology data were retrospectively gathered for patients diagnosed with iCCA, HCC, or liver metastases assessed using liver needle biopsies. Three study groups with an equal number of cases (n = 65) were formed. In the iCCA group, CK19, CA19-9, CK7, and CEA demonstrated the highest sensitivities (100%, 100%, 93.7%, and 82.6%, respectively). The most relevant stains used for diagnosing HCCs were Glypican 3, CD34 (sinusoidal pattern), and Hep Par 1, with corresponding sensitivities of 100%, 100%, and 98.2%. The immunohistochemical panels for diagnosing metastatic tumors were chosen after correlating the clinical data and morphologic H&E aspects. Moderate/intensely positive CK7 expression and absent/low amount of intratumoral immune cells were favorable prognostic factors and correlated with increased overall survival in both the univariate analysis and the multivariate regression adjusted for age, existence of cirrhosis, number of tumors, and tumor differentiation.