Type A Thymoma with Spinal and Cranial Metastases: A Case Report.

Introduction: While metastases of malignant thymomas have been shown, type A thymomas are often treated as benign. Type A thymomas often have excellent response to treatment, low recurrence rate, and a small malignant potential. To date, there have been no reports of type A thymomas with spinal metastases. Case Report: A 66-year-old female with a type A thymoma metastatic to the T7 and T8 vertebral bodies and brain, with associated pathologic burst fracture, collapse of T7, and significant focal kyphosis . The patient underwent successful T7-T8 posterior corpectomy and T4-T11 posterior spinal fusion. At 2 years of follow-up, she was ambulating without assistive devices and completed spinal radiation and initial chemotherapy. Conclusion: Metastatic type A thymoma is a rare phenomenon. While traditionally thought to have low recurrence rates and overall excellent survival rates, our case suggests that the biologic malignant potential of a type A thymoma may not be fully understood.

The Epithelial-Stromal Microenvironment in Early Colonic Neoplasia.

Stromal cells play a central role in promoting the progression of colorectal cancer. Here, we analyze molecular changes within the epithelial and stromal compartments of dysplastic aberrant crypt foci (ACF) formed in the ascending colon, where rapidly developing interval cancers occur. We found strong activation of numerous neutrophil/monocyte chemokines, consistent with localized inflammation. The data also indicated a decrease in interferon signaling and cell-based immunity. The immune checkpoint and T-cell exhaustion gene PDCD1 was one of the most significantly upregulated genes, which was accompanied by a decrease in cytotoxic T-cell effector gene expression. In addition, CDKN2A expression was strongly upregulated in the stroma and downregulated in the epithelium, consistent with diverse changes in senescence-associated signaling on the two tissue compartments. IMPLICATIONS: Decreased CD8 T-cell infiltration within proximal colon ACF occurs within the context of a robust inflammatory response and potential stromal cell senescence, thus providing new insight into potential promotional drivers for tumors in the proximal colon.

Small bowel T-cell lymphoma: a MEITL-ing diagnosis.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), previously known as Type-II enteropathy-associated T-cell lymphoma (EATL), is a rare subset of relatively aggressive lymphoma with a poor prognosis. We present a case of a previously healthy 59-year-old male with a 2-week history of abdominal distention who was found to have a non-bleeding ulcerated segment in the proximal jejunum secondary to MEITL. This exceedingly rare type of lymphoma usually presents with non-specific symptoms and can be challenging to diagnose. Our case demonstrates the importance of understanding the endoscopic and histological findings to allow the prompt diagnosis and treatment of this aggressive disease.

Characterization of Mucosal Dysbiosis of Early Colonic Neoplasia.

Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesions in the colon that can be detected by high-definition chromoendoscopy with contrast dye spray. Although frequently associated with synchronous adenomas, their role in colorectal tumor development, particularly in the proximal colon, is still not clear. The goal of this study was to evaluate the profile of colon-adherent bacteria associated with proximal ACF and to investigate their relationship to the presence and subtype of synchronous polyps present throughout the colon. Forty-five subjects undergoing a screening or surveillance colonoscopy were included in this retrospective study. Bacterial cells adherent to the epithelia of ACF and normal mucosal biopsies were visualized by in situ hybridization within confocal tissue sections. ACF showed significantly greater heterogeneity in their bacterial microbiome profiles compared with normal mucosa. One of the bacterial community structures we characterized was strongly correlated with the presence of synchronous polyps. Finally, using DNA mass spectrometry to evaluate a panel of colorectal cancer hotspot mutations present in the ACF, we found that three APC gene mutations were positively associated with the presence of Instestinibacter sp., whereas KRAS mutations were positively correlated with Ruminococcus gnavus. This result indicates a potential relationship between specific colon-associated bacterial species and somatically acquired CRC-related mutations. Overall, our findings suggest that perturbations to the normal adherent mucosal flora may constitute a risk factor for early neoplasia, demonstrating the potential impact of mucosal dysbiosis on the tissue microenvironment and behavior of ACF that may facilitate their progression towards more advanced forms of neoplasia.

Metastatic cholangiocarcinoma in a patient with undiagnosed Wilson disease.

Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy. Although the frequency of malignancy is generally increased in chronic liver disease, CC rarely presents in Wilson disease (WD). The incidence of hepatic malignancy in WD is only 1.2%, with CC accounting for 0.5%. A 66 year old male with history of hypertension, diabetes, and compensated cryptogenic cirrhosis presented with acute onset dyspnea and pleuritic chest pain. He was incidentally found to have a sizeable mass in the right hepatic lobe. Ultimately, a liver biopsy revealed dense demoplasia and increased mucin production, consistent with diagnosis of CC. Biopsy also demonstrated increased copper deposition consistent with WD, explaining the patient's underlying cirrhosis. Unlike other forms of chronic liver disease where incidence of liver cancer is increased, the lower rate of malignancy seen in WD may be explained by a protective effect of copper in WD. Copper acts to both directly stabilize DNA and inhibit angiogenesis. In this case, it is possible that the degree of copper deposition in his liver was mild, causing cirrhosis and the chronic liver inflammation that caused his CC. However, it may not have been sufficient to "protect" against development of CC.

Subcutaneous metastasis from recurrent basaloid squamous cell carcinoma of the esophagus.

BACKGROUND: Esophageal cancer is the 11th most common cause of cancer mortality in the United States. It is aggressive in nature and has an ability to spread rapidly through direct extension, lymphatic spread, or hematogenously. With an estimated incidence of 1%, cutaneous metastases from esophageal cancer are extremely rare. CASE PRESENTATION: In this case study and review, we describe a case of recurrent esophageal basaloid squamous cell carcinoma presenting as multiple, rapidly progressing and tender subcutaneous nodules. A 69-year-old male with history of basaloid squamous cell carcinoma of the esophagus treated with concurrent chemoradiation, presented to his oncologist with complaints of a large, painful nodule at the nape of his neck approximately two years after completing treatment. On further examination, he was noted to have multiple, well circumscribed, solid, tender nodules on his abdominal wall along with a painful nodule on the pulp of his index finger. Histopathology from all sites revealed skin infiltration by high-grade invasive basaloid subtype of squamous cell carcinoma, similar to patient's prior known and treated primary esophageal cancer. Further imaging work up showed extensive metastatic disease involving lung, liver, and brain. CONCLUSION: Esophageal squamous cell carcinoma rarely metastasize to the skin. Subcutaneous nodules can be the first presentation of recurrent disease. The lesions are commonly confused with skin infections and treated inappropriately with antibiotics, leading to delay in diagnosis of recurrent disease. Early biopsy of suspicious lesions should be performed, especially in patients with history of cancer, such that prompt diagnosis and treatment can occur to maximize patient outcomes.

Endoscopic Features of Mucous Cap Polyps: A Way to Predict Serrated Polyps.

BACKGROUND/AIMS: The aims of the study were to identify whether a mucous-cap predicts the presence of serrated polyps, and to determine whether additional endoscopic findings predict the presence of a sessile serrated adenomas/polyp (SSA/P). METHODS: We analyzed 147 mucous-capped polyps with corresponding histology, during 2011-2014. Eight endoscopic features (presence of borders, elevation, rim of debris, location in the colon, size ≥10 mm, varicose vessels, nodularity, and alteration in mucosal folds) of mucous-capped polyps were examined to see if they can predict SSA/Ps. RESULTS: A total of 86% (n=126) of mucous-capped polyps were from the right sided serrated pathway (right-sided hyperplastic [n=83], SSA/Ps [n=43], traditional serrated adenoma [n=1]), 10% (n=15) were left-sided hyperplastic polyps, and 3% (n=5) were from the adenoma-carcinoma sequence. The presence of a mucous cap combined with varicose vessels was the only significant predictor for SSA/Ps. The other seven characteristics were not found to be statistically significant for SSA/Ps, although location in the colon and the presence of nodularity trended towards significance. CONCLUSIONS: Our study suggests that mucous-capped polyps have high predictability for being a part of the serrated pathway. Gastroenterologists should be alert for a mucous-capped polyp with varicose veins, as these lesions have a higher risk of SSA/P.

Proximal Aberrant Crypt Foci Associate with Synchronous Neoplasia and Are Primed for Neoplastic Progression.

Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion found within the human colon. Despite their relatively high frequency in the distal colon, few studies have examined the molecular characteristics of ACF within the proximal colon. In the following study, clinical participants (n = 184) were screened for ACF using high-definition chromoendoscopy with contrast dye-spray. Following pathologic confirmation, ACF biopsies were subjected to laser capture microdissection (LCM), and epithelial cells were evaluated for somatic mutations with a customized colorectal cancer mutation panel using DNA-mass spectrometry. Samples were further characterized for microsatellite instability (MSI). Logistic models were used to associate proximal ACF with synchronous (detected during the same procedure) neoplasia. Thirty-nine percent of participants had at least one histologically confirmed proximal ACF. Individuals with a proximal ACF were significantly more likely to present with a synchronous neoplasm (P = 0.001), and specifically, a proximal, tubular, or tubulovillous adenoma (multivariable OR = 2.69; 95% confidence interval, 1.12-6.47; P = 0.027). Proximal ACF were more likely to be dysplastic (52%) compared with distal ACF (13%; P < 0.0001). Somatic mutations to APC, BRAF, KRAS, NRAS, and ERBB2 were detected in 37% of proximal ACF. Hyperplastic ACF were more often MSI-high, but there were no differences in MSI status observed by colonic location. In summary, ACF are identified in the proximal colons of approximately 40% of individuals undergoing chromoendoscopy and more often in patients with synchronous proximal adenomas.Implications: This study provides the most complete set of data, to date, that ACF represent the earliest step in the adenoma-carcinoma sequence but remain below the detection limit of conventional endoscopy.Visual Overview: http//mcr.accrjournals.org/content/molcanres/16/3/486/F1.large.jpg Mol Cancer Res; 16(3); 486-95. ©2017 AACR.

Primary Follicular Lymphoma of the Gastrointestinal Tract: Case Report and Review.

PURPOSE: Primary gastrointestinal follicular lymphoma (GI-FL) is considered a rare disease with fewer than 400 cases reported in the literature. It accounts for roughly 1-3 % of GI non-Hodgkins lymphomas (NHL). It originates in the GI tract and typically affects small bowel. The disease has an indolent course, and a prolonged survival can be expected in most cases. Due to its rarity, an optimal diagnostic work up and treatment plan has not been well established. METHODS: Endoscopic evaluation of the entire gastrointestinal (GI) tract using esophagogastroduodenoscopy (EGD), wireless capsule endoscopy, double-balloon enteroscopy, colonoscopy, and whole body examination with fluorodeoxyglucose-positron emission tomography (FDG-PET) has been suggested to more accurately stage the disease and guide the treatment plan. RESULTS: Treatment options for GI follicular lymphoma include watch and wait strategy, surgery, chemotherapy, radiation, immuno-radiotherapy, or a combination of these modalities. CONCLUSION: In this article, we have summarized the existing information regarding clinical presentation, diagnostic evaluation, and treatment options for this rare entity after presenting a case of GI-FL who was diagnosed during an EGD for evaluation of belching, heartburn, and weight loss.

Hematospermia and Cloacogenic Transitional Cell Carcinoma: A Twist on Significance and Meaning.

A 52-year-old gentleman presented with recurrent hematospermia. Further history revealed recent onset of constipation and difficulty voiding. Rectal examination revealed a firm, polypoid mass and colonoscopy showed suspicious, ulcerated lesions of the rectal mucosa with narrowing of the rectal vault. Pathology demonstrated transitional cell carcinoma of the rectum. While transitional cell carcinoma is a common genitourinary cancer, its presence in the anus and rectum is exceedingly rare. Furthermore, hematospermia is generally not associated with malignancy. This case is a remarkable example of two pathologic processes presenting in rare form and underscores the value of a thorough investigation of hematospermia when associated with other clinical symptoms.

Lipoid Pneumonia and Sarcoidosis.

INTRODUCTION: Lipoid pneumonia is a rare, underdiagnosed disorder, and its combined presentation with sarcoidosis is even more unusual. METHODS: This paper presents a case in which both lipoid pneumonia and sarcoidosis were present, and includes the relevant literature review on lipoid pneumonia. RESULTS: Lipoid pneumonia may be acute or chronic in its presentation, resulting from exogenous or endogenous factors, or classified as idiopathic, with its precise incidence unknown. Radiographic changes maybe variable, but typically include lower lobe consolidation. Pathologic changes consist of an inflammatory giant cell reaction around lipid-related empty vacuoles and giant cell granulomas. Treatment in the case of exogenous lipoid pneumonia consists of removal of the offending oil ingestion. However, in endogenous lipoid pneumonia, treatment is aimed at the underlying cause, as there is no standard treatment. Repeated bronchoalveolar lavage, corticosteroids, and surgical resection have been used as therapies. The course of the disease is usually not progressive.

Colorectal polyp prevention by daily aspirin use is abrogated among active smokers.

PURPOSE: Based on suggestive findings from a recent study of high-risk Japanese patients, we sought to determine whether the risk of colorectal polyps associated with smoking may be modified by daily use of aspirin in an analysis of a large US screening population. METHODS: This is a cross-sectional study of 2,918 consecutive colonoscopy patients at a university hospital over a 30-month period. Data were abstracted from electronic medical records. Multivariate models of polyp counts were used to examine the competing risks of smoking and aspirin use. Models were further stratified by polyp location (proximal vs. distal) and pathologic subtype (dysplastic vs. serrated). RESULTS: Incidental rate of polyps was higher among active smokers [incidence rate ratio (IRR) 1.72; 95 % confidence interval (CI) 1.46-2.02] and lower among daily aspirin users (IRR 0.73; 95 % CI 0.61-0.86) compared to those who used neither. Smoking interacts significantly with aspirin use resulting in loss of aspirin protection (IRR 1.69; 95 % CI 1.28-2.24). Stratified analyses demonstrate that aspirin specifically reduces the risk of traditional dysplastic adenomas (IRR 0.72; 95 % CI 0.61-0.86) not serrated/hyperplastic polyps (IRR 0.92; 95 % CI 0.72-1.17) and that the modification of aspirin protection by smoking is primarily observed within the distal colorectum (p < 0.03). CONCLUSIONS: We report for the first time, in a typical risk US clinical population, a lack of protective association of aspirin for polyps among active smokers. Future prospective studies are recommended to confirm this mitigating effect in order to improve the precision of the growing evidence base about the chemopreventive benefit of aspirin in colorectal cancer.

A review of methotrexate-associated hepatotoxicity.

Methotrexate is effective not only in treating psoriasis and rheumatoid arthritis but also various other disorders. The use of methotrexate has been somewhat limited by concerns regarding its adverse effects, including its potential for hepatotoxicity. The purpose of this article is to provide an overview of methotrexate-associated hepatotoxicity, including risk factors, pathogenesis and recommendations for monitoring it by US, UK and European guidelines, as well as providing a brief overview of its mechanism of action and of high-dose methotrexate.

Second harmonic generation imaging distinguishes both high-grade dysplasia and cancer from normal colonic mucosa.

BACKGROUND AND AIM: Second harmonic generation (SHG) is a novel imaging technology that could provide optical biopsy during endoscopy with advantages over current technology. SHG has the unique ability to evaluate the amount of extracellular matrix collagen protein and its alignment. METHODS: Hematoxylin- and eosin-stained slides from colon biopsies (normal, low-grade dysplasia (LGD), high-grade dysplasia (HGD), and cancer) were examined with SHG imaging. Both signal intensity and collagen fiber alignment were measured. Average intensity per pixel (AIPP) was obtained, and an analyzing polarizer was used to calculate ß, an alignment parameter. RESULTS: The mean AIPP for normal mucosa was 48, LGD was 38, HGD was 42, and malignancy was 123 (p < 0.01). The AIPP ROC curve between malignant versus non-malignant tissue was 0.96 (0.93-0.99). An AIPP value of 60 can differentiate malignancy with 87 % sensitivity and 90 % specificity. The mean ß for normal tissue was 0.490, LGD was 0.379, HGD was 0.345, and cancer was 0.453 (p = 0.013), with a normal tissue mean rank of 6.5 compared to 2.5 for HGD (p = 0.029). CONCLUSIONS: SHG signal intensity can differentiate malignant from non-malignant colonic polyp tissue with high sensitivity and specificity. Anisotropic polarization can discern HGD from normal colonic polyp tissue. SHG can thus distinguish both HGD and malignant lesions in an objective numeric fashion, without contrast agents or interpretation skills. SHG could be incorporated into endoscopy equipment to enhance white light endoscopy.

Rheumatoid nodules in the thyroid bed following total thyroidectomy: a case report.

INTRODUCTION: Rheumatoid nodules occur in 30 percent of patients with active rheumatoid arthritis. Common sites include the buttocks or the extensor surface of the forearm, with one group documenting their presence in the thyrohyoid membrane. To the best of our knowledge, rheumatoid nodules have not been described in the thyroid bed. CASE PRESENTATION: We present the case of a 46-year-old Caucasian woman with active rheumatoid arthritis and Hashimoto's thyroiditis who presented with compressive neck symptoms. An ultrasound scan revealed that both lobes of her thyroid were enlarged. The right lobe measured 7.9×3.4×3.3cm and the left 8.3×3.3×3.1cm. A solitary 1.0×0.6×0.8cm nodule was seen in the right lower lobe. Her thyroid-stimulating hormone level was 4.22uU/mL (0.34 to 5.60). A total thyroidectomy was performed due to her symptoms and the possible growth of a nodule when on levothyroxine. A postoperative ultrasound scan showed no remaining thyroid tissue. The pathology revealed several small neoplasms ranging from a well-encapsulated adenoma to highly atypical follicular and papillary Hurthle cell lesions in the setting of Hashimoto's thyroiditis. Low-dose radioactive iodine (33.4mCi) was given. Four months later, our patient complained of a feeling of fullness in her neck. A solid nodule of mixed echogenicity (5.6×3.3×2.3cm) was seen in the right level VI of the neck, and solid tissue of mixed echogenicity (2.9×2.3×1.7cm) on the left. Following repeat surgery, the pathology from the right specimen showed Hashimoto's thyroiditis. The left specimen had areas of granuloma formation with fibrinoid necrosis and palisading histiocytes, consistent with the histology of rheumatoid nodules. No evidence of malignancy was seen. The patient continues to do well and remains disease-free. CONCLUSIONS: Rheumatoid nodules have not been reported in the thyroid bed. Their pathogenesis is not clear. Postoperative release of tumor necrosis factor alpha and local vascular damage may have triggered the nodule formation in this case. Rheumatoid nodules must be kept in the differential diagnosis of an enlarging thyroid in the setting of active rheumatoid arthritis. A fine-needle aspiration biopsy may show granuloma formation and be the most cost-effective initial diagnostic step, especially if there is a concern for malignancy. Early identification of these nodules will help decrease morbidity from unnecessary interventions and result in treatment that is both timely and appropriate.

An ironic case of liver infections: Yersinia enterocolitis in the setting of thalassemia.

A 49 years old Vietnamese male with a history of thalassemia, presented with gastrointestinal symptoms and signs of hemolysis. He was diagnosed with yersinia enterocolitis. Yersinia is a gram-negative rod that most frequently occurs in children especially during the winter months. In the current case, the bone marrow biopsy showed hemophagocytosis along with positive cultures for Yersinia. The microorganism likely triggered hemophagocytosis. This syndrome, also known as, hemophagocytic lymphohistiocytosis, is defined by fever for more than 7 d, cytopenia of two or more cell lines, hemophagocytosis, hepatitis, serum ferritin greater than 500, jaundice, lymphadenopathy, and hepatosplenomegaly. This disorder can be either familial or secondary to a strong immunologic activation. Both have an overwhelming activation of T-cells and macrophages.

Case report and review of esophageal lichen planus treated with fluticasone.

Lichen planus is a fairly common chronic idiopathic disorder of the skin, nails and mucosal surfaces. Esophageal involvement of this disease on the other hand is rare and only about 50 cases have been reported in literature. Given its rarity, it can be difficult to diagnose and may be easily misdiagnosed as reflux esophagitis. Currently, there are no clear recommendations on the optimal management of this disease and little is known about the best treatment approach. Systemic steroids are usually the first line treatment and offer a favorable response. In this report, we would like to present a novel approach in the management of esophageal lichen planus in a middle-aged woman treated successfully with swallowed fluticasone propionate 220 mcg twice a day for 6 wk, as evidenced by objective clinical findings. Based on our review of related literature and experience in this patient, we feel that a trial of swallowed fluticasone may be a prudent approach in the management of these patients since it has a more favorable side effect profile than systemic treatment.

Hepatic Sarcoidosis.

Sarcoidosis is a multisystem disease characterized by the presence of non-caseating granulomas in affected organs. Pulmonary involvement is the most common site of disease activity. However, hepatic involvement is also common in sarcoidosis, occurring in up to 70% of patients. Most patients with liver involvement are asymptomatic. Therefore, the majority of cases are discovered incidentally, frequently by the finding of elevated liver enzymes. Pain in the right upper quadrant of the abdomen, fatigue, pruritus, and jaundice may be associated with liver involvement. Portal hypertension and cirrhosis are complications linked to long-standing hepatic sarcoidosis. Liver biopsy is usually required to confirm the diagnosis. It is important to differentiate hepatic sarcoidosis from other autoimmune and granulomatous liver diseases. Not all cases of hepatic sarcoidosis require treatment. For symptomatic patients, the first line treatment includes corticosteroids or ursodeoxycholic acid. Various immunosuppressant agents can be used as second line agents. Rarely, severe cases require liver transplantation.

Inflammation associated with neoplastic colonic polyps.

Little is known about the significance of inflammation in neoplastic colon polyps: tubular, tubulovillous, and villous polyps/adenomas (TVPs) and hyperplastic/serrated polyps (HSPs). We undertake this study to ascertain the significance of acute and chronic inflammation in neoplastic polyps. Eighty-one consecutive, randomized TVPs and fifty-four randomized HSPs accessioned in the UCHC surgical pathology laboratory were selected for final analysis. The TVPs display increased acute and chronic inflammation compared to normal and adjacent non-dysplastic colonic mucosa. Adenoma size correlates with degree of acute and chronic inflammation. TVPs show increased overall acute and chronic inflammation compared to HSPs of the same size. This difference was statistically highly significant (p<.001). The number of adenomas exhibiting high grade dysplasia was insufficient to evaluate the relationship between polyp inflammation, polyp size, and degree of dysplasia. The HSPs showed significantly lower incidence and severity of acute and chronic inflammation compared to the TVPs. No correlation was seen in the HSP group between polyp size and acute or chronic inflammation. The prevalence of IBD was higher in patients with HSP showing acute inflammation than in the general population, but this statistic may be skewed by the low overall incidence of acute inflammation in the HSP group.