Metastatic Small Cell Neuroendocrine Carcinoma to the Orbit Manifesting as Total Ophthalmoplegia

PURPOSE@#To report a case of primary ureteral small cell neuroendocrine carcinoma metastasis in the left orbital wall, with a review of the literature.CASE SUMMARY: A 79-year-old male visited our clinic with a 10 day history of ocular pain, ptosis, and ophthalmoplegia in the left eye. He had been diagnosed with diabetes mellitus and was being treated for prostate adenocarcinoma. The corrected visual acuity was 0.8 in the right eye and 0.5 in the left eye. An extraocular movement test showed total ophthalmoplegia, mild exophthalmos, and ptosis in the left eye. Orbital computed tomography (CT) and magnetic resonance imaging showed an irregular mass-like enhancement in the superolateral orbital wall of the left eye, suggesting infectious and inflammatory orbital disease. After antibiotic treatment, high dose systemic steroids were administered. However, there was no improvement and the orbital CT was again performed, with no changes. A surgical biopsy for differentiating orbital tumors was performed and diagnosed as a metastatic orbital small cell neuroendocrine carcinoma. Using positron emission tomography, he was later diagnosed with a metastatic orbital small cell neuroendocrine carcinoma with multiple metastases.@*CONCLUSIONS@#When the patient has a mass-like lesion on imaging with ocular pain, ophthalmoplegia, or ptosis, a surgical biopsy should be performed to make a diagnosis and determine the optimal management.

Prognostic Utility of Histological Growth Patterns of Colorectal Lung Oligometastasis

BACKGROUND: Patients with resectable colorectal lung oligometastasis (CLOM) demonstrate a heterogeneous oncological outcome. However, the parameters for predicting tumor aggressiveness have not yet been fully investigated in CLOM. This study was performed to determine the prognostic value of histological growth patterns in patients who underwent surgery for CLOM. METHODS: The study included 92 patients who were diagnosed with CLOM among the first resection cases. CLOMs grow according to three histological patterns: aerogenous, pushing, and desmoplastic patterns. The growth patterns were evaluated on archival hematoxylin and eosin–stained tissue sections. RESULTS: The aerogenous pattern was found in 29.4% (n=27) of patients, the pushing pattern in 34.7% (n=32), the desmoplastic pattern in 6.5% (n=6), and a mix of two growth patterns in 29.4% (n=27). The size of the aerogenous pattern was significantly smaller than that of metastases with other patterns (p=.033). Kaplan-Meier analysis demonstrated that patients showing an aerogenous pattern appeared to have a poorer prognosis, which was calculated from the time of diagnosis of the CLOM (p=.044). The 5-year survival rate from the diagnosis of colorectal cancer tended to be lower in patients with an aerogenous pattern than in those who had a non-aerogenous pattern; however, the difference was marginally significant (p=.051). In the multivariate Cox analysis, the aerogenous pattern appeared as an independent predictor of poor overall survival (hazard ratio, 3.122; 95% confidence interval, 1.196 to 8.145; p=.020). CONCLUSIONS: These results suggest that the growth patterns may play a part as a histology-based prognostic parameter for patients with CLOM.

Altered Expression of PTEN and Its Major Regulator MicroRNA-21 in Pulmonary Neuroendocrine Tumors

BACKGROUND: Phosphatase and tensin homolog on chromosome ten (PTEN) is one of the most frequently inactivated tumor suppressors in various tumor types. MicroRNA-21 (miR-21) may affect tumor progression by post-transcriptional repression of expression of tumor suppressors, such as PTEN. This study was conducted to evaluate the significance of PTEN expression in pulmonary neuroendocrine (NE) tumors and to analyze the relationship between PTEN and miR-21 expressions. METHODS: Expressions of PTEN and miR-21 were investigated by immunohistochemistry and real time reverse transcription-polymerase chain reaction, respectively, in 75 resected pulmonary NE tumors (23 typical carcinoids [TCs], nine atypical carcinoids [ACs], 22 large cell NE carcinomas [LCNECs], and 21 small cell lung carcinomas [SCLCs]). RESULTS: Loss of PTEN expression was observed in four of 23 TCs (17.4%), four of nine ACs (44.4%), 16 of 22 LCNECs (72.7%) and nine of 21 SCLCs (42.9%) (p=.025). The expression level of miR-21 was significantly higher in high-grade NE carcinomas than in carcinoid tumors (p<.001). PTEN expression was inversely correlated with miR-21 expression (p<.001). CONCLUSIONS: This study suggests that aberrant expression of PTEN in relation to miR-21 may represent an important step in the development and progression of pulmonary NE tumors.

Perimenopausal Ovarian Carcinoma Patient with Subclavian Node Metastasis Proven by Immunohistochemistry

Ovarian cancer is the seventh most common cancer in the world and the fifth most common cause of death from cancer; it is responsible for over half of all deaths related to gynecological cancers. The presence of lymphatic metastasis is an important prognostic factor in ovarian cancer. Nodal metastases to the pelvic and the para-aortic lymph nodes are common, particularly in an advanced of the disease (stages III-IV). The finding of distant nodal metastasis, especially subclavian lymph node metastasis, from ovarian carcinoma is very uncommon. 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) or FDG-PET/computed tomography (CT) provides an improved imaging for detecting metastatic lymph nodes in patients with ovarian cancer. Immunohistochemically, ovarian carcinoma cells are positive for estrogen receptor, progesterone receptor, cancer antigen 125, Wilms' tumor 1 protein, and p53; they are negative for thyroid transcription factor (TTF-1) and caudal-related homeobox 2 (CDX-2). This report describes a Korean woman diagnosed with ovarian cancer with subclavian lymph node metastasis revealed by FDG PET/CT and verified by an immunohistochemical staining. Differentiating between the primary ovarian lesion and the metastatic lesion will allow the initiation of an appropriate treatment and help predict the prognosis.

One Case of a BRCA1 Germ Line Mutation Ovarian Carcinoma Patient Based on Abnormal Immunohistochemistry Finding

No abstract available.

One case of endometrial cancer occurrence: Over 10 years after colon cancer in Lynch family

We have recently experienced an endometrial cancer 12 years after the diagnosis of colon cancer with Lynch syndrome. A 49-year-old Korean woman had a family history of colon cancer. Her mother had colon cancer at 56-year-old, and her brother had colon cancer at 48 years old. The patient received surgery for endometrial cancer at the same hospital 12 years after being treated for colon cancer. Immunohistochemistry showed that her endometrial tissue stained negative for MSH2. A microsatellite instability test was performed and showed the presence of instability high microsatellite instability. An hMLH2 gene mutation was detected at codon 629 codon of exon 12, in which a glutamine was replaced with an arginine (1886A>G [p.Gln629Arg]). To our knowledge, this is the first case of metachronous cancer in a Lynch syndrome family in Korea with a gap of more than ten years between cancer diagnoses.

A Case of Perimenopausal Endometrial Cancer in a Woman with MSH2 Germline Mutation

Lynch syndrome is a genetic malignancy syndrome affecting the colon, endometrium, and other organs. It is difficult to find a Lynch syndrome patient without any family history of cancer. We have recently examined an endometrial cancer patient with a MSH2 gene mutation without a family history of cancer. A 55-year old Korean woman was admitted to a local clinic for vaginal bleeding. An endometrial biopsy revealed the presence of adenocarcinoma (endometrioid type, grade 1). After surgical staging, no further adjuvant therapy was required. Analysis of the tissue using immunohistochemistry (IHC) showed the endometrium stained negatively for MSH2. Microsatellite instability (MSI) was analyzed for five markers. The patient was scored as unstable. Further, additional gene sequencing revealed one missense mutation in c.23C > T (p.Thr8Met). This is the first case of Lynch syndrome endometrial cancer in Korea in which the patient does not have any family history of cancer.

Frequency of BRAF Mutation and Clinical Relevance for Primary Melanomas

BACKGROUND: This study was conducted to clarify the frequency of the BRAF mutation in primary melanomas and its correlation with clinicopathologic parameters. METHODS: We analyzed the frequency of BRAF mutation in patients with primary cutaneous melanoma (n=58) or non-cutaneous one (n=27) by performing dual priming oligonucleotide-based multiplex real-time polymerase chain reaction to isolate and to purify the DNA from the formalin-fixed and paraffin-embedded tumors. RESULTS: The BRAF mutation was found in 17.2% (10/58) of patients with primary cutaneous melanoma and 11.1% (3/27) of those with non-cutaneous melanoma. The frequency of BRAF mutation was not correlated with any clinicopathologic parameters with the exception of the patient age. The frequency of the BRAF mutation was significantly higher in patients younger than 60 years as compared with those older than 60 years (p=0.005). CONCLUSIONS: Compared with previous reports, our results showed that the frequency of the BRAF mutation was relatively lower in patients with primary cutaneous melanoma. Besides, our results also showed that the frequency of the BRAF mutation had an inverse correlation with the age. Further studies are warranted to exclude methodological bias, to elucidate the difference in the frequency of the BRAF mutation from the previous reports from a Caucasian population and to provide an improved understanding of the molecular pathogenesis of malignant melanoma.

Frequency of BRAF Mutation and Clinical Relevance for Primary Melanomas

BACKGROUND: This study was conducted to clarify the frequency of the BRAF mutation in primary melanomas and its correlation with clinicopathologic parameters. METHODS: We analyzed the frequency of BRAF mutation in patients with primary cutaneous melanoma (n=58) or non-cutaneous one (n=27) by performing dual priming oligonucleotide-based multiplex real-time polymerase chain reaction to isolate and to purify the DNA from the formalin-fixed and paraffin-embedded tumors. RESULTS: The BRAF mutation was found in 17.2% (10/58) of patients with primary cutaneous melanoma and 11.1% (3/27) of those with non-cutaneous melanoma. The frequency of BRAF mutation was not correlated with any clinicopathologic parameters with the exception of the patient age. The frequency of the BRAF mutation was significantly higher in patients younger than 60 years as compared with those older than 60 years (p=0.005). CONCLUSIONS: Compared with previous reports, our results showed that the frequency of the BRAF mutation was relatively lower in patients with primary cutaneous melanoma. Besides, our results also showed that the frequency of the BRAF mutation had an inverse correlation with the age. Further studies are warranted to exclude methodological bias, to elucidate the difference in the frequency of the BRAF mutation from the previous reports from a Caucasian population and to provide an improved understanding of the molecular pathogenesis of malignant melanoma.

Diagnostic Utility of Caveolin-1 and MOC-31 in Distinguishing Chromophobe Renal Cell Carcinoma from Renal Oncocytoma

PURPOSE: Renal tumors consist of heterogeneous groups that frequently show complex and overlapping morphology, thus making it difficult to make a correct diagnosis. One of the most problematic differential diagnoses is to distinguish chromophobe renal cell carcinoma (RCC) from oncocytoma. These should be distinguished by differences in their behavior and clinical outcome. Our study was performed to identify whether caveolin-1 and MOC-31 are useful immunohistochemical markers for differentiating chromophobe RCC from oncocytoma. MATERIALS AND METHODS: We selected 23 chromophobe RCCs, 8 oncocytomas, and 25 clear cell RCCs and performed immunohistochemical staining for caveolin-1 and MOC-31. RESULTS: Caveolin-1 was positive in 20 (87%) of 23 chromophobe RCCs, 0 of 8 oncocytomas, and 21 (84%) of 25 clear cell RCCs. MOC-31 was positive in 22 (96%) of 23 chromophobe RCCs, 2 (25%) of 8 oncocytomas, and 14 (56%) of 25 clear cell RCCs. There was a statistically significant difference in the expression of caveolin-1 and MOC-31 between chromophobe RCC and oncocytoma (p<0.001). In addition, clear cell RCC was also significantly different from oncocytoma in the expression of caveolin-1 (p<0.001) and was significantly different from chromophobe RCC in the expression of MOC-31 (p<0.001). CONCLUSIONS: Caveolin-1 and MOC-31 can be useful markers in the differential diagnosis of chromophobe RCC, oncocytoma, and clear cell RCC.

The Interobserver Variability for Diagnosing Pulmonary Carcinoid Tumor

BACKGROUND: Although the grade of pulmonary carcinoid tumor is routinely reported in pathology practice, there is a paucity of data on the level of agreement between pathologists. METHODS: Data for 30 cases of surgically resected pulmonary tumors diagnosed as carcinoid tumors (19 typical carcinoids [TCs] and 11 atypical carcinoids [ACs]) were retrieved from four university hospitals. These cases were independently evaluated by five pathologists and were classified according to the 2004 World Health Organization (WHO) classification. Agreement was regarded as "unanimous" if all five pathologists agreed, and as a "majority" if four agreed. The kappa statistic was calculated to measure the degree of agreement between pathologists. RESULTS: Unanimous agreement was achieved for 50.0% and a majority agreement for 83.3% of the 30 cases. The range of the kappa values extended from 0.37 to 0.89. After a consensus meeting, there was disagreement between the original diagnosis by each institute and the consensus diagnosis by the five pathologists for 40.0% of the 30 cases. Based on the consensus diagnosis, the agreement was greater for TCs than that for ACs. CONCLUSIONS: Discriminating carcinoid tumors is subject to interobserver variability. This study indicates that there is a need for more careful standardization and application of diagnostic criteria for making the diagnosis of pulmonary carcinoid tumor.

Histologic/Immunohistochemical Classification of Carcinoma of the Ampulla of Vater and Survival Rate

PURPOSE: The prognostic factors for carcinoma of the Ampulla of Vater have not been fully identified. This study was undertaken in order to determine whether or not immunohistochemical staining can be used identify the potential diagnostic and prognostic markers for carcinoma of the Ampulla of Vater. METHODS: We studied twenty four patients with carcinoma of the Ampulla of Vater who underwent curative resection from September 1995 to February 2003 at the Department of Surgery, Dong-A University Medical Center. All the specimens were reviewed by an expert pathologist, and immunohistochemical stains were used to differentiate the pathologic type. RESULTS: The overall 5-year survival rate was 58.3%, and survival was closely correlated with the pathologic differentiation. For the immunohistochemical stains, CK20 and MUC2 were significantly effective to differentiate the intestinal type and the pancreaticobiliary type of carcinoma for the Ampulla of Vater (P=0.0162 and P=0.0001, respectively). CONCLUSION: Further investigations with a larger number of cases would enable us to use immunohistochemical stains to improve the differentiation of carcinoma of the Ampulla of Vater.

Immunohistochemical Expression of the Sodium/Iodide Symporter in Patients with Primary Lung Cancer

BACKGROUND: The sodium/iodide symporter (NIS) is a membrane glycoprotein that facilitates the uptake of iodine by thyroid follicular cells. Although the use of radioiodide is essential for the diagnosis and treatment of thyroid diseases, few studies have been conducted to investigate the use of NIS-mediated radioiodide accumulation in lung cancer. We evaluated the expression of NIS by immunohistochemistry in order to examine the diagnostic or therapeutic feasibility of using radioiodide in the treatment of primary lung cancer. METHODS: Immunohistochemistry for NIS was performed in 139 lung cancers. The expression pattern of NIS was compared with the clinicopathological characteristics of the tumors. RESULTS: NIS immunoreactivity was detected in 75 (54.0%) of the 139 cases. Twenty-three (37.7%) of the 61 squamous cell carcinomas, 49 (76.6%) of the 64 adenocarcinomas, 2 (40.0%) of the 5 small cell carcinomas, and 3 (33.3%) of the 9 other carcinomas showed positive NIS immunoreactivity. The expression of NIS was significantly associated with the histologic type (p<0.001), but it did not correlate with tumor size, lymphovascular invasion or lymph node metastasis. CONCLUSIONS: The presence of NIS was detected in lung cancer tissue using immunohistochemistry. Lung cancer potentially could be targeted with radioiodide for both diagnosis and treatment, especially in cases of adenocarcinoma.

Differential Expression of CD34 and Smooth Muscle Actin in the Stroma of Small Lung Adenocarcinoma with Mixed Bronchioloalveolar and Invasive Components

BACKGROUND: Absence of CD34-positive fibroblasts was reported within the stroma associated with invasive carcinomas. Conversely, tumor-associated desmoplastic stroma is characterized by the presence of smooth muscle actin (SMA)-reactive myofibroblasts. The present study was undertaken in order to elucidate whether the different distributions of stromal CD34-positive fibroblasts and SMA-reactive myofibroblasts are sensitive or specific markers of tumor invasion in small lung adenocarcinomas. METHODS: Immunohistochemical stainings for CD34 and SMA were done in 37 peripheral adenocarcinomas less than 3.0 cm in diameter, including 16 adenocarcinomas with bronchioloalveolar carcinoma (BAC) and invasive components (mixed), and 21 invasive adenocarcinomas without BAC components (invasive). RESULTS: The fibroblasts within the BAC components of the mixed group were mainly CD34-positive (81.2%) and preferentially SMA-negative (56.3%). In contrast, the fibroblasts within the invasive components of the mixed group were mainly CD34-negative (75.0%) and SMApositive (87.5%). The stromal cells of the invasive group were mostly negative for CD34 (90.5%) and positive for SMA (95.3%). CONCLUSIONS: The loss of CD34 and the acquisition of SMA in the stromal cells within the tumor were related to tumor invasion (p<0.05). Thus, expression patterns of CD34 and SMA can be used to detect small foci of early stromal invasion in adenocarcinomas of the lung.

Peripheral Micronodular Squamous Cell Carcinoma of the Lung Unexpectedly Discovered after an Operation for Spontaneous Pneumothorax: A Case Report

The occurrence of lung cancer in patients suffering with pneumothorax is very rare, especially in the absence of any radiological changes that would suggest neoplasia after the pulmonary reexpansion. We have experienced a case of a 60-year-old male who presented with lung cancer that was discovered by chance after an operation for his pneumothorax. The resected lung tissue showed a 0.3 cm-sized, peripheral squamous cell carcinoma associated with a bulla. The tumor was not macroscopically detected on the first thoracotomy that was performed for the treatment of the pneumothorax. The micronodular cancer was diagnosed after the histological examination of the resected bulla. The patient has been doing well with no evidence of tumor recurrence during the fifteen months follow-up. This case shows that we should always be vigilant for associated lung cancer when we examine the lung tissue after the operation for pneumotherax.