Whole exome sequencing of a gut-associated lymphoid tissue neoplasm points to precursor or early form of sporadic colon carcinoma.

Gut-associated lymphoid tissue (GALT) carcinoma is a colorectal neoplasm characterized by cystically dilated neoplastic glands that extend into prominent, well-circumscribed submucosal lymphoid tissue. Although often subtle, lamina propria between and around the neoplastic glands (identified by plasma cells, scattered eosinophils, etc.) is frequent in cases with classic morphology, arguing (at least in such cases) in favor of adenoma extending into lymphoglandular complexes rather than true invasive carcinoma. Some have postulated that the tumor arises from M-cells, specialized epithelial cells overlying GALT, and others have suggested it represents a unique pathway to carcinoma, specific to the environmental conditions of epithelium overlying lymphoid tissue. Although both hypotheses are intriguing, definitive phenotypic and genetic support is currently lacking. To address these possibilities, we undertook whole exome sequencing and immunohistochemical characterization of a GALT neoplasm recently identified on our clinical service. We discovered well-known mutations in both APC and KRAS, as well as mutations in several Wnt pathway components (MED12, BCL9L, RFX4, DACT3). No immunohistochemical expression of GP2, a marker of M-cell differentiation, was identified. Expression of CDX2, SATB2, and the DNA mismatch repair proteins was observed, while expression of both CK7 and CK20 was absent. No PD-L1 expression was present on tumor cells, but PD-L1 expression was noted in a subset of tumor-adjacent mononuclear cells. Overall, the findings suggest that GALT neoplasms, although morphologically distinct, may be a precursor or early form of typical sporadic colon carcinoma.

Factors Involved in the Degeneration of Lymphoid Tissue in the Appendix.

INTRODUCTION: Studies evaluating the age-related alteration of human appendix have been reported. Although the appendix shows a degeneration of lymphoid tissues with aging, the mechanism of action remains unclear. MATERIAL AND METHODS: Surgically resected appendix tissues from patients with colon cancer, intestinal malrotation and ulcerative colitis (UC) were utilized for histological and flow cytometric analysis. RESULTS: Histological analysis showed that aging may induce steatotic changes in the appendix. However, there was no clear association between appendiceal fibrosis and aging. Lymphoid follicles in the appendix may start to develop before 5 days of age, gradually mature, and eventually disappear with aging. Flow cytometric analysis clearly identified a lymphocyte population in the appendix at 5 days, 45 and 75 years of age, and lymphoid follicles were also confirmed histologically. In contrast, lymphoid population was rarely detectable in the appendix at 79 and 80 years of age, and no lymphoid follicles were present histologically. Interestingly, cytograms from a case at 5 days of age suggested the existence of immature immune cells, as forward scatter showed an increase in cell size of the lymphocyte population. Histological analysis in UC patients found submucosal fat in the appendix of a case 66 years of age. Lymphoid follicular formation and mucosal structure were disrupted in cases of 70 and 72 years of age. UC patients may be more susceptible to steatotic change. Cytograms from appendices of UC patients also supported these histological findings. Our study confirms previous results that lymphoid tissues in the appendix degenerate over time, and proposes that inflammatory insult may facilitate the degenerative process in patients with UC.

Unilaterally Enlarged Mandibular Foramina and Canal Associated With Hyperplastic Lymphatic Tissue of Inferior Alveolar Nerve: Case Report and Short Literature Survey.

BACKGROUND: Different phenomena can result in enlargement of mental foramen and mandibular canal. At the foreground of diagnosis is the assessment of the biological properties of the tissue which causes such detailed lesions of the skeleton. CASE REPORT: This report describes a palpable mass at the site of the mental foramen with radiological evidence of an extensive enlargement of the bony portion of the inferior alveolar nerve. These findings were the reason for surgical exploration. Surprisingly, the mass was inflammatory tissue that had proliferated in the canal and foramina. The lesion had grown around the nerve and did not infiltrate it. The diagnosis of lymphatic hyperplasia was made. Other potential causes of the unusual radiological and clinical findings are explained with reference to the literature. CONCLUSION: Imaging does not provide a safe assessment of tumor biology. Surgical exploration with detailed tissue examination of the tumor provides the basis for appropriate therapy.

Ablation of nasal-associated lymphoid tissue does not affect focal ischemic brain injury in mice.

Stroke is a devastating disease with a strong inflammatory component. It has been shown that part of this response is mediated by IL17+ γδT cells. γδT cells constitute a lymphocyte population with innate features that mainly populates epithelial surfaces including skin, intestine, and airways. We have shown that in the context of stroke, T cells migrate from the small intestine to the meninges but whether they can migrate from other epithelial surfaces is still unknown. Because of its proximity, one possible source of stroke-associated IL17+ γδT cells could be the Nasal-Associated Lymphoid Tissue (NALT) from which T cells could migrate along olfactory nerve sheaths through the cribriform plate into the brain and/or meninges. In order to study the role of NALT as a source for immune cells and/or inflammatory mediators in the context of stroke, we analyzed the effect of NALT ablation on immune cell infiltration and infarct volume after stroke. Infarct volume analysis did not show any significant difference between sham and NALT-ablated animals. In addition, no significant differences were found in immune cell infiltration in the brain or meninges of stroke animals subjected to NALT or Sham-ablation surgery. In conclusion, NALT ablation does not affect ischemic brain damage or immune cell infiltration in the meninges or brain after stroke.

Clinicopathological features of splenic tumours of lymphoid tissue.

BACKGROUND: To study the effects of splenectomy on treatment and diagnosis of tumours of lymphoid tissue of the spleen. METHODS: Fifty-three cases were reviewed from Peking University People's Hospital from 2002 to 2017. According to WHO classification of tumours of haematopoietic and lymphoid tissues (2008) and classification updated (2016), the cases were studied by microscopy, immunohistochemistry and in situ hybridization, combined with the bone marrow biopsy and clinical examination. RESULTS: In 53 cases, the male to female ratio was 3.4:1, the mean age was 55.4 years old, the median survival time was 17.0 months, and all patients present with variable degree of splenomegaly. The elevated percentage of lymphocyte in peripheral blood can be seen in 22 cases, and elevated LDH level in 24 cases. Abnormal blood counts can be seen in 26 cases before operation, and 22 cases remission to normal level partly or completely after operation. The clinical symptoms included abdominal pain or distension, fatigue, fever, and weight loss, etc. Seventeen cases present with lymphoadenopathy of abdomen or other sites. Fourteen cases were stage I or II, whereas 6 were stage III, 28 were stage IV. Forty-three cases were splenic B-cell marginal zone lymphoma (SMZL)(48.8%,21/43), DLBCL(23.3%,10/43), splenic diffuse red pulp small B-cell lymphoma (SDRPSBL)(11.6%,5/43), mantle cell lymphoma (MCL)(9.3%,4/43), follicular lymphoma (FL)(4.7%,2/43), composite lymphoma (CL, DLBCL and classical Hodgkin lymphoma)(2.3%,1/43) in turn, and the remaining 10 cases were chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL) (n = 4), hairy cell leukaemia (HCL) (n = 1), hepatosplenic T-cell lymphoma (HSTL) (n = 5). The survival period of SMZL and DLBCL was 25.7, 18.6 months, respectively. Thirteen cases were dead (27.1%, 13/48). The chemotherapy protocol included Hyper-CVAD A/B with/without R (Rituximab), COP, CHOP with/without R etc. The prognosis of those with elevated LDH level, high clinical staging, B symptom, and older than 60 year old was obviously worse, and the prognosis of DLBCL was worse than that of SMZL. CONCLUSIONS: Most splenic lymphoid tumors present with splenomegaly and abnormal blood counts, and complete or part remission of blood counts can be seen after splenectomy, and splenectomy is also helpful for pathological diagnosis. The most common pathological types are SMZL and DLBCL. The definite diagnosis can be made by combining with clinical features, histopathology, immunophenotype, genetics, bone marrow biopsy and laboratory examination.

Successful Surgical Treatment of Intractable Chylous Ascites Using the Lymphatic Cable Flap: A Retrospective Review Study.

OBJECTIVE: For evaluation of a novel surgical procedure for the treatment of chylous ascites. Chylous ascites is a debilitating condition associated with high morbidity and mortality rates. At least one-third of patients are refractory to medical therapy and may warrant further treatment. Traditional methods involving ligation of lymphatic fistulas or small bowel resection do not address the basic pathophysiologic mechanism of the underlying obstruction, and identification of chyloperitoneal fistulas may be challenging. METHODS: A novel flap based on deep inferior epigastric vessels with its surrounding lymphatic fatty tissue was designed in this study and transferred into abdominal cavity, with anastomosis to the fourth jejunal vessels. Three consecutive cases with chylous ascites treated by this vascularized lymphatic cable transfer were retrospectively reviewed. RESULTS: All three patients recovered from chylous ascites after the lymphatic cable transfer and tolerated regular diet well, with follow-up of 3 years at least. CONCLUSIONS: Lymphatic cable flap based on the deep inferior epigastric vessels could be a potential option for treatment of intractable chylous ascites, with safe and successful long-term outcomes in three consecutive patients. The proposed functional mechanism of the flap is bypass of the obstructed intra-abdominal lymphatics to an extraperitoneal route as well as local lymphangiogenesis.

Maintaining low non-neoplastic polypectomy rates in high-quality screening colonoscopy.

BACKGROUND AND AIMS: Non-neoplastic polypectomies (NNPs) add pathology and procedural costs but do not reduce cancer risk and should be minimized. We sought to define the minimal non-neoplastic polypectomy rate (NNPR) for those colonoscopists achieving high-quality colorectal cancer screening based on adenoma detection rates (ADRs). METHODS: NNPRs for colonoscopists achieving high-quality adenoma detection rates were reported to determine minimal NNPR goals. Two approaches to tracking NNPR monitoring were compared: (1) total NNPR, an NNPR inclusive of all non-neoplastic specimens with exclusion of only hyperplastic polyp, sessile serrated polyp, and adenoma; and (2) normal tissue-only NNPR, an NNPR inclusive of those specimens with only normal colonic mucosa or lymphoid follicles. RESULTS: For those performing colonoscopy with high-quality ADRs (≥25%), half (6/12) of the colonoscopists had a total NNPR of ≤8.5% and 2 gastroenterologists had a total NNPR of ≤3.4%. The mean total NNPR of the cohort was 8.7% versus the normal tissue only NNPR, which was 7.5% (mean difference of 1.2%, standard deviation ± 0.97). The widest variation between total NNPR versus normal tissue only NNPR for any colonoscopist was 2.9%. The total NNPR ranged between 2.6% and 21.3% among 14 colonoscopists. CONCLUSIONS: Colonoscopy with a high-quality ADR can be achieved while maintaining a low total NNPR. A total NNPR, inclusive of all non-neoplastic specimens as an alternative to an approach in which all specimens require individual review in order to select out only normal tissue can be considered for monitoring of NNPR.

Endoscopic submucosal resection of gastric subepithelial lesions smaller than 20 mm: a comparison of saline solution-assisted snare and cap band mucosectomy techniques.

BACKGROUND AND AIMS: Application of endoscopic submucosal resection (ESMR) in the management of gastric subepithelial lesions (GSLs) less than 20 mm is gradually increasing because it allows diagnosis and treatment at the same operative session. In this study, we compare and evaluate the benefits of ESMR with an endoscopic cap band mucosectomy technique or saline solution-assisted snare technique in GSLs smaller than 20 mm. METHODS: This was a retrospective analysis of a prospectively maintained database used at 2 academic tertiary care centers. A total of 63 patients (34 females, mean age 52 years) with endoscopically resected GSLs were included in this study. RESULTS: The mean tumor size determined by EUS was 12.3 mm (range, 5-20 mm). Sixty-seven percent of the GSLs were localized in the antrum in all groups. The endoscopic cap band mucosectomy technique was used to resect 32 (50.8%) GSLs, whereas 31 (49.2%) were resected with the saline solution-assisted snare technique. The en bloc resection rates were 97% for the saline solution-assisted snare technique and 100% for the endoscopic cap band mucosectomy. Intraoperative bleeding occurred in 1 of 31 patients (3.2%) when ESMR was performed with the saline solution-assisted snare technique. Postoperative bleeding was seen in 1 of 32 patients (3.1%) who underwent the endoscopic cap band mucosectomy technique. CONCLUSIONS: In GSLs smaller than 20 mm, ESMR with saline solution-assisted snare or endoscopic cap band mucosectomy techniques is safe, the adverse event rate is low, accurate diagnosis is achieved, and treatment with en bloc resection is provided in a single session. Given similar success and adverse event rates, saline solution-assisted ESMR may be the preferred technique because of its lower cost advantages.

DOME/GALT type adenocarcimoma of the colon: a case report, literature review and a unified phenotypic categorization.

Several types of colorectal cancers are associated with a prominent lymphoid component, which is considered a positive prognostic factor. We report a case of a dome-type carcinoma of the cecum in a 57 year old female. The sessile, non-polypoid lesion histologically consisted of a tubulovillous adenoma with low-grade dysplasia. The submucosal invasive component showed low-grade architectural features that included cystically dilated glands containing eosinohilic debris. Immunohistochemical studies displayed retention of the four mistmach repair proteins, consistent with a stable phenotype. After 3 years, the patient remains free of recurrence. A literature review highlighted striking similarities between dome-type carcinoma and the gut-associated lymphoid tissue carcinoma, the two sharing an intimate association with the gut associated lymphoid tissue.The two variants might therefore be grouped into a unified category.

Rectal tonsil: a case report and literature review.

The rectal tonsil, a reactive proliferation of lymphoid tissue located in the rectum, is rare. Histologically, benign lymphoid hyperplasia of the rectum is usually characterized by large lymphoid follicles with active germinal centers and a narrow surrounding mantle zone and marginal zone. This lesion is benign, but must be differentiated from the polypoid type of mucosa-associated lymphoid tissue lymphomas. In the current paper, we present a case of rectal tonsil in a 59-year-old woman. We describe the endoscopic ultrasound imaging findings with literature review.

Robotic partial adrenalectomy using indocyanine green dye with near-infrared imaging: the initial clinical experience.

OBJECTIVE: To present the initial clinical experience with robot-assisted partial adrenalectomy using indocyanine green dye with near-infrared fluorescence (ICG-NIRF) imaging. METHODS: Three consecutive patients with solitary adrenal masses with worrisome features were referred for treatment. The preoperative workup included dedicated axial imaging and adrenal function studies. All patients underwent purely robotic partial adrenalectomy with ICG-NIRF guidance. Relevant steps of the technique included a transperitoneal approach, gross identification of the adrenal gland, administration of 5 mg intravenous ICG, and finally, mass resection guided by ICG-NIRF and white light visualization in an effort to completely excise the mass while sparing uninvolved adrenal tissue. RESULTS: Robotic partial adrenalectomy was successfully performed with negative margins in all patients. All masses were hypofluorescent relative to normal adrenal tissue with ICG-NIRF and included a pheochromocytoma, lipoadenoma, and follicular lymphoid hyperplasia. CONCLUSION: Robotic partial adrenalectomy with intraoperative ICG-NIRF is safe and feasible. The addition of ICG-NIRF may help mass identification, excision, and promote the use adrenal-sparing surgery.

The enigma of the lower gut-associated lymphoid tissue (GALT).

Artiodactyls possess GALT that appears in fetal life and is located at the extreme end of the ileum. These IPP contain mostly B cells and involute early in postnatal life. Rabbits have a similarly located lymphoid organ, called the sacculus rotundus. Studies in sheep and rabbits have led to the concept that the lower hindgut GALT represents primary lymphoid tissue for B cells and is necessary for normal B cell development, analogous to the bursa of Fabricius. This review traces the history of the observations and theories that have led to the existing concept concerning the role of lower GALT. We then review recent data from piglets with resected IPP that challenges the concept that the IPP is primary B cell lymphoid tissue and that artiodactyls and rabbits are members of the GALT group in the same context as gallinaceous birds. Eliminating the IPP as the primary lymphoid tissue for B cells leads to the hypothesis that the IPP acts as first-responder mucosal lymphoid tissue.

Primary extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type in the central nervous system (MZL CNS) presented as traumatic subdural hematoma and subarachnoid bleeding - case report.

The study describes a very rare case of primary extranodal marginal zone Bcell lymphoma of the central nervous system (MZL CNS) with an unusual clinical and radiological presentation mimicking subarachnoid bleeding and subdural hematoma (SDH) after head injury. The patient presented symptoms which had commenced 3 weeks earlier: a gradually-progressing headache associated with periodic right-sided cramp of the face muscles and numbness of the right upper limb. During urgent craniotomy for drainage of the presumed SDH, a tumor mass histopathologically and immunohistochemically matching marginal zone B-cell lymphoma was found. Molecular analysis confirmed monoclonal immunoglobulin heavy chain gene (IgH) rearrangement; the patient had previously suspected nodal lymphoma because of cervical lymphadenopathy, but histopathological, immunohistochemical and molecular examination excluded malignant lymphoma. The patient underwent successful radiotherapy, and achieved complete response. At present, no evidence of either systemic disease or lymph node enlargement has been found. The recognition of an indolent type of lymphoma in a rare anatomical localization is very important due to the proper management of the patient.

Development of CD27+ marginal zone B cells requires GALT.

In species other than mouse, little is known about the origin and development of marginal zone (MZ) B cells. Using cross-reactive antibodies, we identified and characterized splenic MZ B cells in rabbits as CD27(+) CD23(-). In rabbits in which organized gut-associated lymphoid tissue (GALT) was surgically removed at birth, we found only CD23(+) follicular (FO) B cells and almost no CD27(+) MZ B cells in the spleen, indicating that GALT is required for the development of splenic MZ B cells. These findings lead us to suggest that commensal microbiota contribute to the development of MZ B cells.

Quiste linfoepitelial en el arco palatogloso / Lymphoepithelial cyst in the palatoglossus arch

The objective of this study was to describe a case of a lymphoepithelial cyst in the palatoglossus arch. A 16-years-old black man said that he was observed a lesion in his mouth. On the physical exam, a pedicled, consistent, smooth surface 1.5 x 1 cm lesion, similar in color to the adjacent mucosa, was found. The lesion was surgically removed and the microscopic exam showed mucosal fragments with pedicled lesion; the cystic cavity sometimes lined with pseudostratified cylindrical epithelium and others with stratified squamous flat interface of the epithelium. Around the cyst, a well-delimited mass of lymphoid tissue, presenting lymphoid follicles, was also seen. Lymphoepithelial cyst has clinical characteristics similar to those of others lesions that occur in the oral cavity. The diagnosis should be based on conservative biopsy, with total removal of lesion(AU)

El objetivo de este estudio fue describir un caso clínico de quiste linfoepitelial en el arco palatoglosso. Paciente de 16 años de edad, sexo masculino, raza negra, que durante la anamnesis relató que observó una lesión en la boca. Al examen físico se observó una lesión pediculada, de consistencia firme, superficie lisa, de 1,5 x 1,0 cm de tamaño, con color similar al de la mucosa adyacente. La lesión fue removida quirúrgicamente y el examen microscópico mostró fragmentos de mucosa con lesión pediculada, la cavidad del quiste a veces revestida por epitelio cilíndrico pseudoestratificado y otras veces por la interfase plana del epitelio escamosa estratificado. Alrededor del quiste, una masa bien delimitada de tejido linfoide con presencia de folículos linfoides. El quiste linfoepitelial tiene las mismas características clínicas de otras lesiones que ocurren en la cavidad oral, el diagnóstico debe ser realizado por biopsia, de manera conservadora, con eliminación total de la lesión(AU)

[Update on special surgical approaches in the therapy for lymphedemas]. / Die Vielfalt in der chirurgischen Therapie beim Lymphödem - was ist aktuell?

Despite recent medical progress primary and secondary lymphedemas still represent a therapeutic challenge and they often lead to a significant reduction in quality of life. Lymphedemas usually develop in the extremities, the male external genitals as well as the female breast as a consequence to the axial alignment of the lymphatic collectors. Early stages are characterized by an excess of lymph fluid increasing the volume of the affected part of the body whereas later stages represent an increasing amount of solid tissue. Thus therapeutic efforts can focus on the reduction of the surplus of liquid and/or solid components. Generally there are conservative and operative strategies. Conservative measures mainly focus on the improvement of fluid mobilization and drainage and comprise compression garments, manual lymphatic drainage, and apparative intermittent compression. Operative approaches comprise procedures for surgical tissue reduction (symptomatic/ablative approaches) and/or procedures with the intention of enhancing lymphatic transport (causal approaches). Surgical tissue reduction can be performed by open resection and/or liposuction. Traditional surgical causal techniques such as transposition of local flaps aim at leading lymph away from the congested region of the body. Modern microsurgical causal approaches contain methods of reconstruction of interrupted lymphatic pathways as well as techniques for the conduction of lymph into local veins. In this review we depict and discuss the features of the multiform spectrum of the surgical therapy of lymphedemas on the basis of literature as well as our own clinical and experimental experience.

[The application of the cryosurgical and lymphotropic technologies for the combined treatment of postintubation tracheal stenosis].

The combined treatment of 10 patients presenting with postintubation thracheal stenosis was carried out with the application of the cryosurgical and lymphotropic technologies. Cryogenic treatment of ciatrical stenosis was performed through the tracheostoma using a titanium nickelide cryoappliactor. The effect of the cryogenic treatment was enhanced by a lymphotropic mixture composed of diprospan and longidaza and administered retrosternally as a course of up to three injections once in a week. In the intervals between the injections and after the termination of the course, the patients were asked to inhale longidaza dissolved in a broncho- or mucolytic preparation through a nebulizer (up to 5 inhalations). All the treated patients reported the recovery of normal breathing through the natural airways.