Background Squamous cell carcinomas (SqCCs) of the lung are known to arise more often in a central area but reports of peripheral SqCCs have increased, with a pathogenesis that is obscured. In this study, the clinicopathologic characteristics of peripheral lung SqCCs were studied and compared with those of the central type.
Methods This study included 63 peripheral lung SqCCs and 48 randomly selected central cases; hematoxylin and eosin-stained slides of surgically resected specimens were reviewed in conjunction with radiologic images and clinical history. Cytokeratin-7 immunohistochemical staining of key slides and epidermal growth factor receptor (EGFR)/KRAS mutations tested by DNA sequencing were also included.
Results Stages of peripheral SqCCs were significantly lower than central SqCCs (p=.016). Cystic change of the mass (p=.007), presence of interstitial fibrosis (p=0.007), and anthracosis (p=.049) in the background lung were significantly associated with the peripheral type. Cytokeratin-7 positivity was also higher in peripheral SqCCs with cutoffs of both 10% and 50% (p=.011). Pathogenic mutations in EGFR and KRAS were observed in only one case out of the 72 evaluated. The Cox proportional hazard model indicated a significantly better disease-free survival (p=.009) and the tendency of better overall survival (p=.106) in the peripheral type.
Conclusions In peripheral type, lower stage is a favorable factor for survival but more frequent interstitial fibrosis and older age are unfavorable factors. Multivariate Cox analysis revealed that peripheral type is associated with better disease-free survival. The pathogenesis of peripheral lung SqCCs needs further investigation, together with consideration of the background lung conditions.
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Background Distinguishing prostatic stromal invasion (PSI) by urothelial carcinoma (UC) from in situ UC involving prostatic ducts or acini with no stromal invasion (in situ involvement) may be challenging on hematoxylin and eosin stained sections. However, the distinction between them is important because cases with PSI show worse prognosis. This study was performed to assess the utility of double cocktail immunostains with high molecular weight cytokeratin (HMWCK) and GATA-3 to discriminate PSI by UC from in situ UC involvement of prostatic ducts or acini in the prostate.
Methods Among 117 radical cystoprostatectomy specimens for bladder UCs, 25 cases showed secondary involvement of bladder UC in prostatic ducts/acini only or associated stromal invasion and of these 25 cases, seven cases revealed equivocal PSI. In these seven cases with equivocal PSI, HMWCK, and GATA-3 double immunohistochemical stains were performed to identify whether this cocktail stain is useful to identify the stromal invasion.
Results In all cases, basal cells of prostate glands showed strong cytoplasmic staining for HMWCK and UC cells showed strong nuclear staining for GATA-3. In cases with stromal invasion of UC, GATA-3-positive tumor cells in the prostatic stroma without surrounding HMWCK-positive basal cells were highlighted and easily recognized. Among seven equivocal cases, two cases showed PSI and five in situ UC in the prostate. In two cases, the original diagnoses were revised.
Conclusions Our study suggested that HMWCK and GATA-3 double stains could be utilized as an adjunct method in the distinction between PSI by UC from in situ UC involving prostatic ducts or acini.
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BACKGROUND The incidence of papillary thyroid carcinoma (PTC) has been increasing recently and a precise diagnosis is essential for optimal treatment. Ancillary immunohistochemical stains are important for diagnosing some difficult cases. METHODS The dignostic value of CD56, high molecular weight cytokeratin (HMCK), galectin-3 (GAL3), and cytokeratin 19 (CK19) were evaluated to distinguish PTC from other benign thyroid lesions (BTL). We studied 23 cases of papillary thyroid overt carcinomas, 57 papillary thyroid microcarcinomas, five follicular adenomas, five cases of Hashimoto's thyroiditis, and 12 nodular hyperplasias. RESULTS The statistical analysis showed significantly different expressions of CD56, HMCK, GAL3, and CK19 in PTC vs other BTL. The diagnostic specificity of HMCK and CD56 (90.9% and 72.7%, respectively) was higher than that of GAL3 and CK19 (50.0% and 36.4%, respectively). However, the sensitivity of HMCK and CD56 detection (92.5% and 95.0%, respectively) was lower than that of GAL3 and CK19 (98.8% and 100.0%, respectively). The combined use of CD56, HMCK, GAL3, and CK19 showed 87.5% sensitivity, 100.0% specificity, and 100.0% positive predictive value in differentiating PTC from other BTL. CONCLUSIONS Although the differential diagnosis of thyroid follicular lesions are based on histological and cytomorphological criteria, CD56 and HMCK might be useful markers for diagnosing PTC.
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Desmoplastic small round cell tumor (DSRCT) is a rare neoplasm of young adults and it is characterized by polyphenotypic differentiation. We experienced a case of abdominal DSRCT that occurred in a 19-year-old female who presented with painful swelling of her right forearm. The tumor was cytokeratin-negative and it exhibited some tumor cells with intranuclear inclusions. Molecular demonstration of EWS-WT1 fusion transcripts is particularly useful to confirm the diagnosis of DSRCT without epithelial differentiation. We report here on a case of cytokeratin-negative DSRCT that showed an unusual feature of intranuclear inclusions.
Immunohistochemical analysis of 24 paraffin-embedded osteosarcomas was studied to evaluate the expression of simple cytokeratin, basal cytokeratin and epithelial membrane antigen(EMA) according to the histologic subtypes and anatomical locations. Mean age of the patients was 18 years. Anatomical locations of the tumors were femur(8), tibia(10), humerus(4), lumbar spine(1), and zygomatic arch(1). Histologic subtypes included osteoblastic(14), fibroblastic(4), chondroblastic(4), epithelioid(1), and mixed osteoblastic and fibroblastic(1). All were positive in the immunohistochemical stain for vimentin. The expression of cytokeratin and/or EMA was found in 10 cases(41.7%) regardless of anatomical locations and histologic subtypes.
Positive immunoreaction for EMA was demonstrated in osteoblastic(5), chondroblastic(2), epithelioid(1), and mixed osteoblastic and fibroblastic(1) types. Osteoblastic (2), chondroblastic(2), and epithelioid(1) types among them also showed immunoreactivity with anti-simple cytokeratin monoclonal antibody, NCL-5D3. The expression of basal cytokeratin (NCL-LL002) was found in two osteoblastic, one chondroblastic, one epithelioid, and one mixed osteoblastic and fibroblastic types. These findings indicate that cytokeratin and EMA immunoreactivity can not be regarded as an absolute specific marker of the epithelial origin of tumor and may also occur in osteosarcoma.
Pseudomyxoma peritonei often have synchronous appendiceal and ovarian mucinous tumors. There has been considerable debate as to whether the ovarian tumors are secondary to the appendiceal tumor or they are independent primary ovarian tumors. It is important to reveal the primary site for treatment and prognosis of a patient. Five cases of synchronous mucinous tumors of the ovary and appendix were studied. Four cases had pseudomyxoma peritonei and pseudomyxoma ovarii. The ovarian tumors were bilateral in two cases, right in two, and left in one. The ovarian tumors were four mucinous cystadenoma of borderine malignancy and one mucinous cystadenocarcinoma, and the appendiceal tumors consisted of four mucinous tumors of borderline malignancy and one mucinous adenocarcinoma. The histology of the ovarian and appendiceal tumors was similar. Rupture of the tumor was seen in all appendiceal tumors and two ovarian tumors. It has been reported that cytokeratin 7 is a useful marker for distinguishing primary ovarian neoplasms from metastases of intestinal origin. All ovarian and appendiceal tumors showed positive reaction for broad-spectrum cytokeratin, but negative for cytokeratin 7. Based on the clinicopathologic and immunohistochemical features, it should be considered that the appendiceal tumors are primary and ovarian tumors are secondary in the synchronous presentation of the ovarian and appendiceal mucinous tumors.
Cytokeratin 7 has been known to be present in various types of human epithelial cells including the ovarian neoplasms, but not in colon cancers. The antibody to colon ovarian tumor antigen (COTA) has been introduced as a marker of colon and ovarian tumors. The aim of this study was to evaluate the usefulness of cytokeratin 7 and COTA in the differential diagnosis between ovarian primary and metastatic tumors. Nineteen primary ovarian epithelial tumors, seven metastatic carcinomas of the ovary from the stomach, three metastatic carcinomas of the ovary from the colon, one mucinous tumor of the ovary associated with a mucinous tumor of the appendix and pseudomyxoma peritonei, and nineteen colonic and twenty gastric adenocarcinomas were stained with monoclonal antibodies to cytokeratin 7 and COTA. The results are summerized as follows; In the primary ovarian tumors, 94.4% were positive for cytokeratin 7 and 50% were positive for COTA. In the primary colonic adenocarcinomas, 94.7% were negative for cytokeratin 7 and 68% were positive for COTA. In the metastatic ovarian tumor from the colonic adenocarcinomas, 100% were negative for cytokeratin 7 and positive for COTA. In the primary gastric adenocarcinomas, 40% were negative for cytokeratin 7 and 85% were negative for COTA. In the metastatic ovarian tumor from the gastric adenocarcinomas, 43% were negative for cytokeratin 7 and 14% were negative for COTA. From the results of this study, it could be concluded that in the differential diagnosis of primary ovarian tumors from metastatic colonic carcinomas, positive reaction for cytokeratin 7 suggests a primary ovarian tumor but a negative reaction for cytokeratin 7 and positive reaction for COTA suggest metastatic colonic carcinomas. The results of this study also reveal that cytokeratin 7 and COTA are not useful in the differential diagnosis of primary ovarian tumors from metastatic gastric carcinomas.
The distinction between cholangiocarcinoma (CC) and metastatic colonic adenocarcinoma of the liver (MCA) is often difficult, particularly in needle biopsy and fine-needle aspiration specimens, if histologic features alone are used. To examine the differences in the expressions of the cytokeratin (CK) 7 and 20 in the CCs and MCAs, we performed immunohistochemical studies on surgically resected 19 CCs and 23 MCAs. We used monoclonal antibodies against CK 7 and CK 20, and applied microwave antigen retrieval technique on formalin-fixed, paraffin-embedded tissue. We interpreted diffuse cytoplasmic reactivity found in > or =5% of tumor cells as positive. CCs showed CK 7+/CK 20- immunophenotype in 63%, CK 7+/CK 20+ in 32%, CK 7-/CK 20+ in 5%, and CK 7-/CK 20- in 0%. MCAs exhibited CK 7-/CK 20+ immunophenotype in 87%, CK 7+/CK 20+ in 9%, CK 7-/CK 20- in 4%, and CK 7+/CK 20- in 0%. CK 20-reactive cells in CCs were frequently columnar in shape (p<0.05). In conclusion, the CK 7/CK 20 immunophenotype was useful in the differentiation of CCs from MCAs: the CK 7+/CK 20- immunophenotype strongly suggested CCs, whereas the CK 7-/CK 20+ immunophenotype strongly suggested MCAs.
The distinction of carcinomas involving periampullary region is often difficult, even in the surgically resected specimens. To examine the differences in the expressions of cytokeratin (CK) 7 and 20 in the periampullary carcinomas, we performed immunohistochemical studies on surgically resected 20 pancreatic duct adenocarcinomas (PDA), 13 distal bile duct adenocarcinomas (DBA), 10 duodenal adenocarcinomas (DA), and 18 ampulla of Vater adenocarcinomas (AVA). We analyzed the relationships between CK 7/CK 20 immunoprofile, and tumor cell differentiation and tumor size. We interpreted diffuse cytoplasmic reactivity found in > or =5% of tumor cells as positive. In the majority of cases, PDA were CK 7 /20 (95%), DBA CK 7 /20 (92.3%), DA either CK 7 /20 (40%) or CK 7 /20 (30%), AVA either CK 7 /20 (50%) or CK 7 /20 (44.4%). In DA, there was an increased CK 20 negativity in less differentiated (moderately or poorly differentiated) cases (p<0.05) and in larger (> or =5 cm) tumor size (p=0.049). In AVA, there was a tendency of increased CK 20 positivity in less differentiated cases (p=0.10). In conclusion, the CK 7/CK 20 immunophenotype is useful in the differentiation of periampullary carcinomas: the CK 7 /CK 20 immunophenotype strongly suggests DA or AVA, whereas the CK 7 /CK 20 immunophenotype suggests PDA or DBA.
There have been some controversies on prognostic significance of lymph node (LN) micrometastasis (MM) in advanced gastric carcinomas (AGCs). The present study aimed at 1) determination of prognostic significance of MM, 2) evaluation of the relationship between MM and clinicopathological parameters, and 3) determination of LN group where MMs were frequently found. We studied 70 cases of AGC without LN metastasis on initial examination. The tumors were examined for location, size, depth of invasion, differentiation, histologic type, lymphatic invasion, and c-erbB-2 expression. To evaluate MM, pancytokeratin immunohistochemistry was performed in all LNs from 70 cases of AGCs. Among 2,203 dissected LNs from 70 patients, 37 (1.6%) LNs from 19 (27.1%) patients revealed MM. Micrometastases were seen in only group 1 and 2 LNs: none had group 3 and 4 LN involvement. The gender, age, tumor size, location of tumor, histologic type, differentiation, depth of invasion, lymphatic invasion, and c-erbB-2 expression were not significantly associated with MM status. The survival time of the MM-positive group (mean: 62 months) was significantly shorter than that of the MM-negative group (mean: 72 months) (p=0.046). The findings of this study indicate that the presence of MM in LNs is an important prognostic factor in AGC patients.
BACKGROUND Basal-type cytokeratins may help to distinguish benign from malignant intraductal proliferative lesions. The basal-type cytokeratins expression is markedly decreased or absent in atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and invasive ductal carcinomas (IDC). However, the expression patterns vary according to the antibodies that are used for staining. METHODS HMW-CK (clone 34 E12) was applied to 175 lesions, and CK5/6 (clone D5/16B4) was applied to 145 lesions. The specimens were IDC (n=165), DCIS (n=35), ADH (n=37), florid ductal hyperplasia (FDH) (n=38) and columnar cell lesion (CCL) (n=45). The expression patterns of HMW-CK and CK5/6 were categorized as negative, focal positive and positive. RESULTS Loss of the HMW-CK expression was noted in 76% (66/87) of the IDC, 78% (21/27) of the DCIS, 78% (21/28) of the ADH, and 55% (10/18) of the FDH. Loss of the CK5/6 expression was found in 96% (75/78) of the IDC, in all the DCIS (n=8) and ADH (n=9), and in none of the FDH (n=20).
Loss of the CK5/6 expression is more reliable than that of the HMW-CK expression for differentiating FDH, ADH and malignant intraductal proliferatve lesions. Eleven (73%) of 15 CCLs revealed the loss of the HMW-CK expression, but all the CCLs (n=30) were negative for CK5/6 (p=0.0161). CONCLUSION CK5/6 antibody is more reliable than HMW-CK antibody for differentiating FDH from ADH or DCIS, and for discriminating CCL.
Immunohistochemical staining for cytokeratins can detect false negative nodes in patients with breast carcinoma. We report on a patient with breast carcinoma and pseudometastasis detected by immunohistochemical staining within a negative sentinel lymph node. A 66-year-old woman underwent a simple mastectomy and sentinel lymph node biopsy. Immunohistochemical staining of the sentinel nodes for cytokeratin in permanent sections showed cells with intense cytoplasmic staining in the subcapsular sinus. The cells were negative for epithelial membrane antigen staining, but positive for CD68. In combination with morphologic findings and immunohistochemistry, cytokeratin-positive cells were confirmed as histiocytes with phagocytized cytokeratin debris. Careful correlation with histology and additional IHC could help avoid a misinterpretation of this type of pseudometastasis.
Low-grade adenocarcinomas that primarily arise within the sinonasal tract are uncommon tumors. We report here on three cases of primary sinonasal low-grade adenocarcinomas. The patients were 2 females and 1 male with ages of 48, 57 and 64, respectively. Microscopically, the tumors had a well developed tubulopapillary growth pattern that consisted of columnar or pseudostratified cells with eosinophilic cytoplasm, round to oval nuclei and rare mitotic activity.
On immunohistochemistry, the tumor cells were strongly positive for cytokeratin 7, but they were negative for cytokeratin 20, CDX-2 and p53. The Ki-67 labeling index was very low (mean: 1.9%). Two patients developed recurrent tumors at the primary site after the initial surgery, but all the patients are presently alive without metastasis 6 years 8 months, 8 years 8 months, and 11 months after the initial diagnosis. When considering the progress of these tumors, we think that it's important to understand the pathology of this entity to avoid underdiagnosis because a complete excision is required for effective treatment.
BACKGROUND The expressions of galectin-3, cytokeratin 19, p53, and Ki-67 in papillary carcinoma (PC), follicular carcinoma (FC), follicular adenoma (FA), and nodular hyperplasia (NH) are characteristic for the differential diagnosis between benign and malignant thyroid tumors. METHODS The expressions of the four markers were evaluated in PC (n=37), FC (n=12), FA (n=22), and NH (n=23) by immunohistochemical staining. RESULTS Statistical analyses revealed that galectin-3 was significantly expressed in the malignant tumor cells of PC and FC, while CK19 was expressed only in PC. CONCLUSION These results show that galectin-3 is useful in differential diagnosis between malignant and benign thyroid lesions, especially between FC and FA in the patients over 20 years old, and indicate that CK19 is valuable in differentiating between follicular variant of PC and FC and between PC and papillary area of nodular hyperplasia.
Odontogenic gingival epithelial hamartoma (OGEH) is an extremely rare lesion characterized by an abnormal proliferation of odontogenic epithelium. This lesion is thought to arise from the rest of the dental lamina lying dormant in the gingival tissue after odontogenesis.
Distinguishing OGEH from the granular cell variant of ameloblastoma and central odontogenic fibroma is important.
To date, only eleven cases have been reported, and its pathogenesis remains unclear. We report here on a case of OGEH, where the epithelial strands in the lesion were conspicuously positive for the antisera of cytokeratin 19 and ameloblastin. Tumor cells intensely expressed ameloblastin mRNA by in situ hybridization. To the best of our knowledge, this is the first case of OGEH to which ameloblastin immunohistochemical stain and in situ hybridization were applied. Although our study is limited to a single case, the coexpression of cytokeratin 19 and ameloblastin might indicate the origin and specific cytodifferentiation of OGEH is quite different and unique, when contrasted to other odontogenic tumors.