Leiomyosarcoma mimicking acute appendicitis: a cautionary tale!

Appendiceal neoplasms are rare, occurring in <1.4% of all appendicectomy specimens. Carcinoid tumours and adenocarcinomas comprise the majority of cases, however, lymphomas or sarcomas may also arise within the appendix. Appendiceal leiomyosarcomas are rare and to date, there remains a relative dearth of cases reported in the literature. Leiomyosarcomas are derived from the smooth muscle cells or mesenchymal stem cells committed to this line of differentiation. However, their pathogenesis and underlying genetic mechanism remains to be fully elucidated. Unbalanced karyotypic defects are the only shared features observed across different leiomyosarcoma subtypes. Children with AIDS have a higher incidence compared with adults, where the main pathology in individuals with HIV is Kaposi's sarcoma and B-cell lymphoma. Although surgical excision with clear margins remains the treatment of choice, a good response to treatment with gemcitabine, docetaxel and trabectedin has been observed. The authors present the case of a 23-year-old female presenting to the emergency department with acute appendicitis. She underwent a laparoscopic converted to an open appendectomy. Her operation was complicated by a pelvic collection requiring percutaneous drainage and an ileus. Histopathological examination confirmed the diagnosis of a leiomyosarcoma, a rare mesenchymal tumour presenting in individuals with immune suppression. HIV serology was positive and she commenced anti-retroviral therapy. She remains under review in the Department of HIV Medicine.

Appendix Tumor Microenvironment.

The pathological features of the appendix tumors fundamentally recall those of the more frequent colorectal neoplasms, although with a higher relative incidence of carcinoids, due to the abundant presence of enteroendocrine cells in the appendix wall. Moreover, different types of lymphomas, Hodgkin and non-Hodgkin, arising from the extra-nodal mucosal-associated lymphatic tissue, can be encountered. The appendix tumor microenvironment (TME) consists of a cellular component and of a noncellular component: the former includes the immunocompetent cells, while the latter represents the support stroma. Particularly in carcinoids, the immune cell reaction can be explicated by tumor-infiltrating lymphocytes, which, in some circumstances, may arrange around and inside the tumor in a brisk fashion influencing favorably the prognosis. This active reaction has to be distinguished from any preexisting inflammatory condition of the appendix and from superimposed tumor complications, such as infection or ischemia. In practice, we consider the appendix TME a complex framework with immunological, mechanic, and metabolic functions, all supported by a marked neo-lymphoangiogenesis.

Post-transplant Lymphoproliferative Disorder of Appendix Mimicking Acute Appendicitis: A Case Report.

Post-transplant lymphoproliferative disorder (PTLD) can be Epstein-Barr virus (EBV)-positive lymphoproliferations occurring in the first year after transplantation or EBV-negative lymphoma occurring many years after transplantation. Both B-cell and T-cell type of PTLD are described in the literature. In the gastrointestinal tract, the small and large intestine are the common sites of involvement. PTLD of the appendix is a lesser-known entity and cases described previously presented clinically as acute appendicitis. We report a case of EBV-negative B-cell PTLD of the appendix mimicking acute appendicitis in a live young renal allograft recipient 7 years after transplantation.

Clinical utility of elevated tumor markers in patients with disseminated appendiceal malignancies treated by cytoreductive surgery and HIPEC.

BACKGROUND: Appendiceal malignancies with peritoneal spread have been successfully treated with Cytoreductive Surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study is to clarify the utility of common tumor markers in selecting patients for the combined treatment. METHODS: Data on 56 patients with appendiceal neoplasms treated with CRS and HIPEC were prospectively collected. Chi square test was used to analyze a link between common tumor markers and completeness of cytoreduction score (CC score) and preoperative peritoneal cancer index score (PCI score). Cox proportional hazard model was used to perform survival analysis. RESULTS: Forty-two patients were alive after 3 years of follow-up. Hazard ratio of disease related death was 5.6 (95% CI, 1.8-17.2) among patients with high CC score as compared to those with low CC score. Number of abnormal tumor markers (0 vs 1/2/3) correlated with PCI score 16.2 vs 32.5 (p < 0.001) but not with completeness of cytoreduction or survival. The 3-year survival rates in patients with normal vs abnormal CA 125 levels were 83% vs 52%(p = 0.003). CONCLUSIONS: Multiple abnormal tumor markers were not useful as an exclusion criterion for patients undergoing CRS. Elevation in CA 125 was an important indicator of survival in these patients. Complete cytoreduction was crucial for long-term survival.

Pathologic classification and clinical behavior of the spectrum of goblet cell carcinoid tumors of the appendix.

Appendiceal tumors exhibiting both neuroendocrine and glandular differentiation are uncommon and have caused difficulty in pathologic classification, prediction of prognosis, and clinical management. Previously, such lesions have been variously designated as adenocarcinoid, goblet cell carcinoid (GCC), and mixed adenocarcinoma carcinoid. In this study, we undertook a retrospective investigation of 63 such cases and classified them as typical GCC (group A) and adenocarcinoma ex GCC on the basis of the histologic features of the tumor at the primary site. The adenocarcinoma ex GCC group was further divided into signet ring cell type (group B) and poorly differentiated adenocarcinoma type (group C). The clinical characteristics and prognosis were compared within these groups and with conventional de novo appendiceal adenocarcinomas. Both groups A and B tumors shared a similar immunoprofile, which included generally focal immunoreactivity for neuroendocrine markers, and a normal intestinal type mucin glycoprotein profile (negative MUC1 expression and preserved MUC2 immunoreactivity). The proliferative index was relatively low in these tumors and slightly increased from groups A to B tumors (11% to 16%). Both beta-catenin and E-cadherin exhibited a normal membranous staining pattern in groups A and B tumors. The poorly differentiated adenocarcinomas ex GCC (group C) demonstrated abnormal p53 and beta-catenin immunoreactivity. The mean follow-up time was 49+/-5 (SE) months. The overall disease-specific survival for all subtypes was 77%, with 46% of patients without evidence of disease and 31% alive with disease. The mean survival was 43+/-7 months. All the patients with clinical stage of I or IIA disease had a favorable outcome after appropriate surgery with or without chemotherapy. Although most patients (63%) with GCC presented at an advanced clinical stage, their clinical outcome could be differentiated by subclassification of tumors. The stage IV-matched 5-year survival was 100%, 38%, and 0% for groups A, B, and C, respectively. In conclusion, GCC is a distinctive appendiceal neoplasm that exhibits unique pathologic features and clinical behavior. They display a spectrum of histologic features and possess the potential to transform to an adenocarcinoma phenotype of either signet ring cell or poorly differentiated adenocarcinoma types. Careful evaluation of the morphologic features of GCCs and appropriate pathologic classification are crucial for clinical management and prediction of outcome. Surgical management with right hemicolectomy is recommended after appendectomy for most cases, particularly those with an adenocarcinoma component (groups B and C).

Synchronous occurrence of carcinoid tumour of the appendix and T-cell lymphoma of the ileum. A case report with review of the literature.

Carcinoid tumours of the gastrointestinal tract are often associated with other tumour types at various sites. However, only rarely has a lymphoma constituted the second tumour. In the present paper, we report the case of a 62-year-old woman who was operated on for a perforated T-cell lymphoma of the ileum and in whom an appendicular carcinoid tumour was incidentally discovered at surgery. It was possible to completely remove both tumours and postoperatively the patient underwent CHOP treatment. Ten months after surgery the patient is well, with no tumour manifestations. We also discuss problems concerning classification of the lymphoma on account of loss of the T-cell antigen CD45RO (UCHL-1).

Goblet cell carcinoid of the appendix endoscopically diagnosed and examined with p53 immunostaining.

We report a case of a 62-year-old woman with goblet cell carcinoid of the appendix. She was admitted to our hospital in September 1994 after the discovery of liver tumors. After admission, a tumor in the right kidney and multiple tumors in the liver were found. She was diagnosed with renal cell cancer and metastasis to the liver and underwent excision of the kidney and enucleation of the largest liver tumor. Histological examination revealed that the liver tumor was a metastatic carcinoid tumor. As carcinoid tumors have frequently been found in the appendix, endoscopic examination was performed and a lesion was found in the appendix by colonoscopy. As predicted, the biopsy specimen was a carcinoid tumor, and she underwent an appendectomy. Histologically, the tumor was a goblet cell carcinoid. Goblet cell carcinoid is a rather rare neoplasm that has the histologic features of both carcinoids and adenocarcinoma. Forty-two cases of goblet cell carcinoid of the appendix have been reported thus far in Japan. However, few were diagnosed via endoscopic examination before surgical operation. We also carried out an immunohistochemical study with anti p53 antibody on the goblet cell carcinoid tumor of the appendix. Most tumor cells were strongly positive, while in three benign carcinoid tumors investigated simultaneously they were negative. These findings suggest that goblet cell carcinoid has an aggressive phenotype compared with benign carcinoid tumors.

Immunohistochemical evidence supporting the appendiceal origin of pseudomyxoma peritonei in women.

Women with pseudomyxoma peritonei (PMP), characterized by multifocal mucinous implants (disseminated peritoneal adenomucinosis), 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 are independent primary ovarian tumors; the latter are usually classified as mucinous tumors of low malignant potential (MLMP). It has been reported that cytokeratins (CK) 7, 18, and 20, carcinoembryonic antigen (CEA), and human alveolar macrophage 56 (HAM-56) are useful markers for distinguishing primary ovarian neoplasms from metastases of intestinal origin. Nearly all primary ovarian MLMP tumors and mucinous carcinomas are positive for CK 7, 18, and 20, CEA, and HAM-56, whereas most colorectal adenocarcinomas are negative for both CK 7 and HAM-56 and positive for CK 20 and CEA. Thirteen appendiceal and 14 ovarian mucinous tumors from 14 cases of PMP and 11 primary ovarian MLMP tumors were studied immunohistochemically for expression of CK 7, 18, and 20, monoclonal and polyclonal CEA (mCEA and pCEA), and HAM-56. Of 14 cases of PMP, 10 (71.4%) had identical staining patterns for all antibodies in both the appendiceal and ovarian tumors. For eight of these, the pattern of immunoreactivity was characterized by negative reactions for CK 7 and HAM-56 and positive reactions for CK 18 and 20, mCEA, and pCEA. One additional case for which only the ovarian tumor could be stained had the same pattern. The remaining two cases were also positive for CK 18 and 20 and CEA, but in addition were positive for CK 7. Two cases were discordant only for CK 7 and one case was discordant for both CK 7 and HAM-56. All 11 MLMP tumors were positive for CK 7 and 18, and pCEA. Eight (72.7%) of 11 were positive for HAM-56, mCEA, and CK 20. There was a statistically significant difference in the frequency of immunoreactivity for CK 7 (p = 0.0005) and HAM-56 (p = 0.0002) between the ovarian mucinous tumors in PMP and the MLMP tumors, with the ovarian tumors in PMP tending to be negative for CK 7 and HAM-56, similar to the appendiceal adenomas. Most ovarian mucinous tumors in PMP demonstrate a pattern of immunoreactivity with CK 7, 18, and 20, CEA, and HAM-56 that is identical to the associated appendiceal adenoma and distinct from primary ovarian MLMP tumors, consistent with the interpretation that these ovarian tumors are secondary to the appendiceal tumor.

Estimates of radiation absorbed dose for intraperitoneally administered iodine-131 radiolabeled B72.3 monoclonal antibody in patients with peritoneal carcinomatoses.

Using a newly available model for determining estimates of radiation absorbed dose of radioisotopes administered intraperitoneally, we have calculated absorbed dose to tumor and normal tissues based on a surgically controlled study of radiolabeled antibody distribution. Ten patients with peritoneal carcinomatosis received intraperitoneal injections of the murine monoclonal antibody B72.3 radiolabeled with 131I. Biodistribution studies were performed using nuclear medicine methods until laparotomy at 4-14 days after injection. Surgical biopsies of normal tissues and tumor were obtained. The marrow was predicted to be the critical organ, with maximum tolerated dose [200 rad (2 Gy) to marrow] expected at about 200 mCi (7.4 GBq). In patients with large intraperitoneal tumor deposits, the tumor itself is an important source tissue for radiation exposure to normal tissues. Local "hot-spots" for tumor-absorbed dose were observed, with maximum tumor-absorbed dose calculated at 11,000 rad (11 Gy) per 100 mCi (3.7 GBq) administered intraperitoneal; however, tumor rad dose varied considerably. This may pose serious problems for curative therapy, especially in patients with large tumor burdens.

[Mucinous cystadenocarcinoma of the appendix. A rare tumor of the right iliac fossa]. / Cystadénocarcinome mucineux de l'appendice. Une tumeur rare de la fosse iliaque droite.

An observation of a mucinous cystadenocarcinoma of the appendix, in the tumor form, revealed by a painful syndrome of the right iliac fossa in a 62-year man is reported. It is a rare malignant tumor as less than 0.5% of the appendicectomy parts present a malignant mucosecreting tumor. In our observation, the diagnosis was allowed by pre-operation imaging. An increase of the serous amount in the tumor markers (carcinoembryonic antigen) (CEA) and CA 19-9 was found before the intervention and the immunodetections performed on the operation part were positive for CEA and CA 19-9. The serous amounts of these markers were normalized after operation. To the author's knowledge, the interest of dosing the serous tumor markers in the observation of such a type of tumor is not mentioned in the literature. The recurrences are frequent and sometimes late even when the initial excision has been macroscopically satisfactory. A new increase of the serous amount of the markers could allow for an earlier detection of a recurrence during the patient follow-up. At present, the prognosis of these malignant forms remains very poor as the 5-year survival does not exceed 25%.

Occurrence and expression of cytokeratins in carcinoid tumours of the gastrointestinal tract and their probable precursor cells.

Occurrence and expression of cytokeratins were studied by the immunoperoxidase-antiperoxidase (PAP) technique in formalin-fixed, paraffin embedded material from 18 cases of carcinoid tumours of the gastrointestinal tract. Polyclonal antikeratin for wide spectrum screening was detected in 12 cases; low molecular weight cytokeratins, C19 and CAM5.2 were positive in majority of the cases whereas antikeratins for high molecular weight were negative in all. Similar positive immuno-reactivity with antibodies to cytokeratins were detected in the surrounding epithelial cells. These results suggest that carcinoids of the gastrointestinal tract originate from the endodermal stem cell and differentiates along one or more directions, and the immunohistochemical findings depend upon the direction of their differentiation.

Neuromas of the appendix. A light-microscopic, immunohistochemical and electron-microscopic study of 20 cases.

The neural origin and even the existence of appendiceal neuromas have been questioned. We have studied 20 examples, 7 discovered during a prospective examination of 26 consecutive routine appendectomy specimens (for an incidence of 27%), 2 selected from random cases, and 11 discovered in a retrospective review of 11 randomly selected cases of appendices diagnosed as "fibrous obliteration." By light-microscopy, appendiceal neuromas appear as a loose proliferation of spindle cells usually in a myxoid background, frequently with entrapped fat and connective tissue and infiltrated by eosinophils. Seventeen were located centrally in the appendix without nodule formation. One was central with nodularity and two were confined to the mucosa. The spindle cells were positive for S-100 protein and neuron-specific enolase in all cases. In 12, serotonin positive cells entrapped in the proliferation were present. In 5 of 11 cases with apparent uninvolved appendix present in the specimen, the number of serotonin cells in the crypts was greater than in normal appendix controls. Two appendiceal neuromas contained somatostatin positive cells. Stains for vasoactive intestinal polypeptide, substance P, neurotensin, bombesin and gastrin were negative. Ultrastructural examination of one case confirmed the presence of a mixture of Schwann cells and cells containing neurosecretory granules. We conclude that appendiceal neuroma is a rather common entity, and that most cases of so-called fibrous obliteration actually represent appendiceal neuroma.

Mucinous carcinoid tumor of the appendix presenting as bilateral ovarian tumors.

Mucinous carcinoid tumor of the vermiform appendix, an uncommon variant of appendiceal carcinoid, may present clinically with ovarian metastases. We studied a tumor by immunohistochemistry and electron microscopy and reviewed eight similar cases from the literature. The primary and metastatic tumors in our case were composed of mucin-producing cells and small argyrophilic cells arranged in cords and acini. Tumor cells in both primary and metastatic sites exhibited identical patterns of immunoreactivity for epithelial antigens (epithelial membrane antigen, carcinoembryonic antigen) and neuroendocrine antigens (serotonin, vasoactive intestinal polypeptide, adrenocorticotropic hormone). Ultrastructurally, the cells contained either mucin vacuoles or dense-core neurosecretory granules; rare individual cells contained both types of inclusions. When bilateral solid mucinous ovarian tumors are discovered at laparotomy, diagnostic appendectomy is indicated if no obvious extraovarian primary tumor can be found.