Palisading granulomas associated with lung cancer

A granulomatous response to neoplastic structures was found in three cases of resected small-cell anaplastic carcinoma of the lung. This consisted of almost continuous rims of palisading epithelioid cells surrounding viable, necrotizing, and necrotic tumor nests. None of the patients had received chemotherapy or radiation treatment prior to surgery, and no clinical, microbiological, or histological evidence of tuberculosis, fungal infection, or rheumatoid disease was found. The granulomatous rim seems to be a response to spontaneous tumor decay.     

Neutrophils and TRAIL: insights into BCG immunotherapy for bladder cancer

Bladder cancer is a huge economic burden on the healthcare system and is responsible for approximately 5% of all cancer deaths in humans. Mycobacterium bovis BCG-based therapy is the treatment of choice for superficial bladder cancer. Bacillus Calmette-Guerin (BCG) instillation in the bladder results in a massive local inflammatory response that has secondary antitumor properties. Recent studies have demonstrated that neutrophils present in the bladder after BCG instillation release large amounts of the apoptosis-inducing molecule TRAIL, as well as chemokines that recruit other immune cells, suggesting that neutrophils play a key role in the antitumor response to BCG therapy. This review discusses the impact of these findings on the understanding of the antitumor mechanisms underlying BCG-based immunotherapy for bladder cancer.     

Hepatic granulomas following ileal bypass for obesity

A review of liver biopsy specimens from patients undergoing ileojejunal bypass for obesity showed granulomas in follow-up biopsy specimens from six of 25 patients (24%) three months to four years after the procedure. The incidence was significantly greater than that seen in obese patients at the time of surgery (4%), (P less than .02). Their origin could not be attributed to systemic infections, medications, or nutritional factors. It would seem that hepatic granulomas in such patients may be due to factors associated with the surgical procedure.     

Cutaneous granulomatous response to BCG cell walls with reference to cancer immunotherapy.

A chronic inflammatory response produced by cell walls of Mycobacterium bovis strain BCG associated with microscopic oil droplets (BCG CW-O) was studied with reference to the tumor-regressing ability of this preparation. When BCG CW-O was injected intradermally in the footpads of guinea pigs, intense inflammation developed at the site of injection and in the draining popliteal lymph node. This was characterized histologically as granulomatous inflammation. The intensity of the response was related to the dose of BCG CW-O. Cell walls without oil produced the same type of inflammation but much less in degree. Data are presented that demonstrate the immunological nature of this response and classify it as a cell-mediated immune reaction. Ramifications of this chronic inflammatory reaction occurring at the site of a tumor are discussed.     

Hepatic lesions induced by systemic chemotherapy for digestive cancer

The anticancerous chemotherapies are often responsible for toxic injury of the nontumoral liver. Two types of histological lesions were recently reported during the treatment of digestive cancers: the sinusoidal obstruction syndrome (SOS); or veno-occlusive disease associated with the use of oxaliplatine, and steatohepatitis associated with the use of irinotecan. The SOS is a cause of increased postoperative morbidity, particularly during major hepatectomy or when more than six cycles of chemotherapy are administered. Steatohepatitis increases the postoperative morbidity and mortality. The new targeted molecules do not seem to modify the postoperative course. Hepatic injury and postoperative complications associated with chemotherapies used in the treatment of digestive cancers are summarized in this review.     

Hepatic granulomas, with an emphasis on infectious causes

Granulomas are aggregates of macrophages, often admixed with other inflammatory cells, which usually result from chronic antigen presentation. Many diseases that produce granulomas involve the liver. Some are intrinsic hepatic diseases, whereas others are disseminated systemic diseases that involve the liver and other organs. Hepatic granulomas are reportedly present in 2% to 10% of all liver biopsy specimens examined in general practice, and of those supposedly as many as 36% have no discoverable etiology even after extensive evaluation of the specimen. This review focuses on the diagnosis of granulomas in infectious diseases affecting the liver, including use of special stains, serologic studies, and molecular diagnostic techniques, and discusses pertinent noninfectious causes of hepatic granulomas that are in the differential diagnosis.     

Necrobiotic palisading granulomas associated with breast carcinoma

AIMS: The presence of granulomas within the stroma of carcinomas and in the lymph nodes draining carcinomas has been well described. To date, however, there have been few studies examining the occurrence and relevance of necrobiotic granulomas occurring in association with breast carcinoma.METHODS/RESULTS: Four cases of breast carcinoma with necrobiotic granulomas were examined using periodic acid Schiff and Ziehl Neelsen stains for fungi and tubercle bacilli and with immunohistochemistry using CAM 5.2, cytokeratin 7, and cytokeratin AE1/3 for tumour cells. In one case the stroma was involved, in the other three cases the lymph nodes contained necrobiotic granulomas. In two of the cases, one with stromal and one with lymph node involvement, the necrobiotic granulomas contained necrotic tumour cells.CONCLUSION: In this study the features of four cases of breast carcinomas with necrobiotic granulomas are examined and their relevance explored. Close scrutiny of such granulomas is necessary to avoid underdiagnosis of metastatic disease.     

Epstein-Barr virus infection and hepatic fibrin-ring granulomas

Hepatic fibrin-ring granulomas were the main histological finding in the liver of a 38-year-old man with Epstein-Barr virus primary infection. The patient presented with fever, hepatomegaly, icterus, abnormal liver tests, autoimmune hemolytic anemia, and mononucleosis syndrome. There was neither enanthema nor lymphadenopathy or splenomegaly. Serologic tests disclosed an Epstein-Barr primary infection profile: anti-viral capsid antigen IgM antibodies and anti-early antigen antibodies were present, whereas anti-Epstein-Barr nuclear antigen antibodies were absent. There was no evidence for Q fever, Hodgkin's disease, or allopurinol-induced hepatitis, which are recognized causes of hepatic fibrin-ring granulomas. It is suggested that Epstein-Barr virus infection might be an additional cause of these peculiar hepatic granulomas.     

The long-term evolution of mycobacterial BCG and preformed immune complex BCG/anti-BCG granulomas in rats

In previous studies it was found that infections with BCG or complexed BCG/anti-BCG in rat skin produced granulomas that appeared to resolve at 8 months. In this follow-up study 1 year later, it appeared that while lesions due to preformed complexes had resolved, those due to BCG alone had undergone a massive reactivation. Nevertheless despite the loss of CMI the infection was restricted. The bacilli, present in enormously increased numbers, were dead; the host macrophages were large and activated. Epithelioid cells and dendritic cells were common. The granuloma was confluent, with patchy necrosis and inconspicuous polymorph infiltration. Although preformed complexes with viable bacilli formed at equivalence had produced a resolving lesion, the outcome of the natural infection was complicated by an imponderable balance of immunological responses. CMI does not appear to have been a determinant during the crucial phases of the infection.     

Marked infiltration of eosinophils in necrotizing granulomas in the resected hepatic bed after cholecystectomy resulting from gallbladder cancer and metastatic liver cancer is associated with peculiar peripheral eosinophilia

It is known that after transurethral resection of the prostate (TUR-P) or a bladder tumor (TUR-BT), necrotizing granuloma formation associated with massive eosinophil accumulation can be detected at the site of the scar, revealing marked eosinophilia. This condition is called post-TUR prostatitis or cystitis. In the present study, we noticed a similar phenomenon in five patients who underwent cholecystectomy, of whom four had gallbladder adenocarcinoma and one had metastatic liver cancer originating from the rectum. We detected necrotizing granulomas with massive eosinophil accumulation, associated with marked eosinophilia. To induce these phenomena, the interval between the first operation (i.e., cholecystectomy) and the second operation (i.e., resection of the hepatic bed and extrahepatic bile duct) is very important. If the interval was 1 week, no granuloma formation was detected. On the other hand, if it was more than 2 weeks, the resected hepatic bed contained necrotizing granulomas with substantial eosinophil accumulation combined with an increase in peripheral eosinophilia (up to 34% in one case). Secondary resection was necessary to induce eosinophilia after cholecystectomy. In this sense, malignancies possessed a relationship with delayed eosinophilia. In the granulomas, some foreign body-type multinucleated giant cells were positive for both anti-interleukin (IL)-5 and CD68 antibodies. In sharp contrast, no eosinophilia was detected after cholecystectomy, with or without hepatic resection consequent to severe adhesion. Clinicians as well as pathologists should keep in mind that these peculiar phenomena of eosinophil accumulation surrounding the necrotizing granulomas and peripheral eosinophilia after cholecystectomy could occur.