Nonleukemic granulocytic sarcoma of kidney with mixed phenotype blasts: a diagnostic dilemma

Granulocytic sarcoma (GS) usually presents concomitantly with or after the onset of acute myeloid leukemia, blastic phase of chronic myeloid leukemia (CML), or myelodysplastic syndromes. Rarely, it may present even before the onset of overt leukemia and when so, it is often misdiagnosed. We are reporting a case of GS of kidney presenting as an isolated renal mass with normal laboratory investigations including a normal peripheral blood smear. It was initially misdiagnosed as lymphoma as the blasts, in addition to the morphological similarity with lymphoma cells, also showed positive immunohistochemistry for B cell markers. Based on further investigations including immunophenotyping and cytogenetic studies, a final diagnosis of CML-blast crisis (mixed phenotype) presenting initially as GS was made. To the best of our knowledge, this is the first antemortem report of nonleukemic GS presenting as kidney mass that later on progressed to CML-blast crisis with mixed phenotype blasts.     

Spinal epidural granulocytic sarcoma preceding acute myelogenous leukemia.

A rare case of spinal epidural granulocytic sarcoma (GS) preceding acute myelogenous leukemia is described. A 10-year-old boy presented with lower leg weakness. The initial diagnosis was a histiocytic lymphoma, and he was treated accordingly. No evidence of bone marrow involvement was found at that time. The correct diagnosis of epidural GS was made possible in retrospect by using immunoperoxidase staining for lysozyme fourteen months later when the patient showed the full-blown features of leukemia. This rare tumor should be considered in the differential diagnosis of an epidural mass with cord compression in patients with or even without acute leukemia, because early diagnosis followed by appropriate combined chemotherapy and radiation may obviate surgical intervention and eventually prevent leukemic transformation.     

Unsuspected gastric granulocytic sarcoma in a patient with myelodysplastic syndrome.

Granulocytic sarcoma (GS) is an uncommon and localized extramedullary tumor composed of immature granulocytic cells. Most GS reported in large series were not associated with overt acute myelogenous leukemia. Gastric perforation occurred during prednisolone therapy in a 72-year-old Japanese male with a four-month history of a myelofibrosis-like state. Subtotal gastrectomy was performed for a suspected gastric ulcer perforation. Gastric histologic, immunohistochemical and cytochemical examination revealed diffuse infiltration by sheets of myeloblasts and promyelocytes with scant or moderately abundant cytoplasm including a few eosinophilic myelocytes. Bone marrow study done in one month after the operation disclosed refractory anemia with excess of blasts (RAEB). Leukemic transformation occurred two months later, and a subcutaneous tumor appeared on the forehead. The forehead tumor predominantly consisted of myeloblasts without evidence of maturation. Both the stomach and forehead tumors were examined immunohistochemically with a panel of monoclonal antibodies (LCA, L26, MT1, UCHL1, OPD4, LN-1, LN-2, LN-3, MB1, Leu-M1, PM) and polyclonal antibodies (lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S-100 protein, lactoferrin), as well as naphthol-ASD-chloroacetate esterase staining to investigate and characterize the reliable marks for GS, and the patient was diagnosed as GS. We found that gastric GS may occur in a myelofibrosis-like state followed by RAEB of myelodysplastic syndrome and that naphthol-ASD-chloroacetate esterase staining and immunohistochemical detection of MT1, lysozyme, and alpha 1-antitrypsin were the most reliable markers for confirming the diagnosis of GS.     

Granulocytic sarcoma of the small intestine

Granulocytic sarcoma is an extramedullary tumor of myeloblasts and/or immature myeloid cells, which can develop at any anatomic site and is often a forerunner to the development of acute myelogenous leukemia. Granulocytic sarcoma of the gastrointestinal tract most frequently involves the small intestine and most often presents with abdominal pain and obstruction. Pathologists must consider granulocytic sarcoma in any mass of unknown origin with a diffusely infiltrating population of tumor cells, as the diagnosis is often initially unrecognized, especially in nonleukemic patients. Multiple ancillary modalities are available to assist pathologists in making the correct diagnosis so that appropriate therapy can be initiated.     

粒细胞白血病患者环核苷酸代谢的研究

通过对２１例粒细胞白血病患者血浆环－磷酸腺苷（ｃＡＭＰ）含量、腺苷酸环化酶（ＡＣ）、环腺苷酸磷酸二酯酶（ＰＤＥ）比活性和环－磷酸鸟苷（ｃＧＭＰ）含量进行检测，并与１８例非白血病患者和２２例正常人血浆ｃＡＭＰ、ｃＧＭＰ含量和ＡＣ、ＰＤＥ比活力进行比较，发现急性和慢性粒细胞性白血病组的ｃＡＭＰ水平显著低于正常对照组（Ｐ〈０．０１）、ＡＣ比活力也显著低于正常对照组（Ｐ〈０．０１）、ｃＧＭＰ水平显著高于正     

Acute hepatitis E: a cause of lymphocytic destructive cholangitis

Lymphocytic destructive cholangitis is a histological pattern associating bile duct intraepithelial lymphocytic infiltration and bile duct epithelial damage. Lymphocytic destructive cholangitis is an important diagnostic feature of primary biliary cirrhosis, but it can also be seen in primary sclerosing cholangitis, autoimmune hepatitis, the so-called overlap syndrome, acute or chronic viral hepatitis C, drug-induced hepatitis, and acute rejection or graft-versus-host disease in liver or bone marrow transplantation. In the present paper we report a case of acute hepatitis with lymphocytic destructive cholangitis on liver biopsy. Clinical and biological examinations showed that the patient had hepatitis E with no other cause of liver disease. Therefore, hepatitis E should be considered as a diagnostic possibility when liver biopsy shows acute hepatitis and lymphocytic destructive cholangitis. The mechanism of bile duct damage in hepatitis E remains unknown.     

Jaundice following high--dose arabinoside cytosine in a child with acute myelogenous leukemia.

A girl with acute myelogenous leukemia (AML) was treated with high dose arabinoside cytosine during consolidation. She developed jaundice twice after the completion of 3 rd and 4 th cycle of the drug. The jaundice was characterized by conjugated hyperbilirubinemia, elevated aminotransferases and alkaline phosphatase. The histologic study of the liver showed only infiltration by mononuclear cells in portal space and scarce bile pigment in some hepatocytes. In both cases jaundice receded spontaneously. Now the patient has been in complete remission for 36 months and subsequent liver function tests are normal.     

Liver Stem/Progenitor Cells in the Canals of Hering: Cellular Origin of Hepatocellular Carcinoma with Bile Duct Tumor Thrombi?

It is generally believed that the invasion of hepatocellular carcinoma (HCC) into the biliary tree ultimately leads to the formation of bile duct tumor thrombi (BDTT). However, recent studies revealed that primary tumor might be small, even undetectable, and there was no histopathologic evidence of direct tumor invasion into bile duct wall in some patients. During the last decade, efforts on stem cell biology may shed light on the pathogenesis of BDTT. Presently, accumulating evidence supports the following notions: (1) the canals of Hering (CoH) are the most likely origin of liver stem/progenitor cells (LSPCs) in adult livers; (2) similar signalling pathways may regulate self-renewal in LSPCs and liver cancer cells, and a substantial proportion of liver tumors may often originate from the transformation of LSPCs; and (3) liver cancer contains rare cells with stem cell-like properties, which could derive from malignant transformation of LSPCs. Herein, we propose that HCC with BDTT, especially with small or undetectable primary lesion and/or no histopathologic evidence for bile duct invasion, might arise from LSPCs residing in the CoH and, possibly, some primary lesions are formed firstly within the intrahepatic biliary tree. When “tumor thrombi” extends mainly along bile duct, there might be “BDTT” alone; when it invades into surrounding parenchyma, there might often be small “primary tumor” with “BDTT”. If this holds true, the putative type may be a particular subset of HCC, and most importantly it would facilitate our understanding of stem-cell origin of HCC.     

Myeloid sarcoma of both kidneys,the brain,and multiple bones in a nonleukemic child

A myeloid sarcoma (MS) is an extramedullary tumor consisting of primitive granulocytic precursor cells. Although most such tumors have been reported in patients with acute myelogenous leukemia, MS is rarely recognized as an isolated tumor without any evidence of leukemia. However, in such cases, the initial diagnosis of MS can be difficult, so initial misdiagnosis rates of up to 75% have been reported. This report describes an unusual case of MS in a 3-year 5-month-old girl presenting as bilateral renal enlargements, and brain masses, with multiple bone involvements, but no hematological abnormalities.     

Preceding orbital granulocytic sarcoma in an adult patient with acute myelogenous leukemia with t(8;21): a case study and review of the literature

A 25-year old man with a 30 month history of proptosis and pain of the right eye was referred to Severance Hospital of Yonsei University. Orbital computed tomography (CT) demonstrated a huge mass in the right retrobulbar orbit; an incisional biopsy and orbitotomy were performed for diagnosis and orbital soft tissue decompression. Subsequent histopathology disclosed sheets of mononuclear cells in the orbital mass, and immunohistochemical stains demonstrated positive results for myeloperoxidase and CD43, which supported the diagnosis of granulocytic sarcoma (GS). After his 1-year follow-up, the patient presented with pancytopenia, and an ensuing bone marrow aspiration revealed markedly hypercellular marrow replaced by many large abnormal myeloblasts. The patient was diagnosed with acute myelogenous leukemia with t(8;21) preceded by orbital GS. Orbital GS is primarily a disease of children, and extremely rare in adults. To the best of our knowledge, only four cases of this disease in adults have been reported in the literature. Our case is the first report of preceding orbital GS in an adult patient with a complex karyotype including t(8;21).     

胆管神经内分泌癌的诊断和治疗

目的 提高对胆管神经内分泌肿瘤的认识。方法 报道国内首例肝总管神经内分泌癌合并肝脏转移，结合国内已经报道的8例未发生转移病例，总结该病的诊断和治疗。结果 男性3例，女性6例，8例以梗阻性黄疸起病，2例合并类癌综合征，梗阻部位胆总管下段2例，肝总管6例，胆总管中段1例，手术前均未能确诊；采取探查性手术，5例行根治性切除胆管空肠吻合术，2例行Whipple手术，1例行姑息切除＋肝动脉插管化疗，1例外引流，手术后病理确诊。结论 胆管神经内分泌癌是一种少见的胆道恶性肿瘤，梗阻性黄疸是常见的症状，NSE、Cg-A、SYP等免疫组化染色是诊断的要点；手术切除率高，根治性切除是治疗的首选，如果肿瘤转移，姑息性切除＋肝动脉化疗是比较好的选择。     

Liver metastasis from rectal cancer with prominent intrabile duct growth

Intrabiliary growth of liver metastases from colorectal cancer has rarely been studied. A surgically resected case of a metastatic liver tumor with prominent intrabiliary growth derived from rectal cancer is reported. The patient was a 62-year-old man who had received a low anterior resection for rectal cancer in March 2000. He was re-admitted due to obstructive jaundice in January 2003, and was diagnosed with hepatic malignancy in segment II of the liver with an intrabiliary tumor extending from the intrahepatic bile duct of segment II to the common hepatic duct. He underwent a left hepatectomy, a partial resection of segment VI, and an extrahepatic bile duct resection with reconstruction of the biliary tract. In the resected specimen, there were whitish tumors of 3 cm and 1.5 cm in diameter in segments II and VI, respectively, and an intrabiliary tumor originating from the main tumor in segment II extended to the common hepatic duct. Both the liver tumors and the intrabiliary tumor consisted of a well- to moderately differentiated adenocarcinoma, which showed the same histological features as the rectal cancer. The immunohistochemical findings strongly supported that these tumors, including the intrabiliary growth, were liver metastasis from the rectal cancer. The intrabiliary invasion and growth of metastatic liver tumors has generally been overlooked, notwithstanding their frequently observed biological behavior. The present case is informative, and further investigation into this type of metastatic liver tumor may be warranted.     

Secondary T-cell lymphoproliferation after marrow transplantation

Secondary lymphoproliferative syndromes in immunosuppressed patients have been characterized as polyclonal or monoclonal B-lineage disorders nearly always associated with Epstein-Barr virus (EBV) infection. The authors now report three patients with a distinctly different lymphoproliferative syndrome. Two patients with common acute lymphoblastic leukemia antigen (CALLA) (CD10)-positive acute lymphoblastic leukemia and one patient with acute myelogenous leukemia, respectively, received high-dose chemoradiotherapy followed by marrow transplantation from either an HLA-identical sibling or HLA-mismatched parent. All three patients developed severe graft-versus-host disease (GVHD), requiring immunosuppressive treatment with corticosteroids. A secondary malignant T-cell lymphoproliferation occurred 2, 21, and 43 months, respectively, after marrow transplantation. In all three cases the lymphoid cells expressed T-cell surface antigens and were morphologically and immunophenotypically distinct from the malignant cells present before transplantation. One tumor was of host cell origin, one was probably of donor origin, and the tumor origin in the third case could not be determined. The authors were unable to find any evidence for EBV, human T-cell lymphotropic virus type I or II, human immunodeficiency virus, or human herpesvirus 6.     

Myeloid sarcoma of the extrahepatic bile ducts presenting as obstructive jaundice

We report a rare case of myeloid sarcoma (MS) of the extrahepatic bile ducts presenting as obstructive jaundice in a patient without leukemia at time of diagnosis. A 75-year-old female presented with a one-month history of abdominal pain and jaundice. Computerized tomography scan of the abdomen showed stenosis of the extrahepatic bile ducts. Endoscopic retrograde cholangiography disclosed an irregular narrowing of the common biliary duct, suggestive of a cholangiocarcinoma, and resection was performed. Histologic examination showed diffuse transmural infiltration of malignant cells. These cells exhibited medium-sized round nuclei with central nucleoli and eosinophilic cytoplasm, and were strongly positive for myeloperoxidase, CD68, lysozyme, CD45, CD117 (c-kit protein) and CD43. Eight months following surgery the patient presented with multiple cutaneous nodules and bone marrow trephine biopsy showed acute myelomonocytic leukemia. A literature search identified two previously reported cases of MS of the extrahepatic biliary duct. MS should be taken into consideration in the differential diagnosis of a patient with obstructive jaundice. Immunohistochemistry is essential for a correct diagnosis.     

Increased Reissner's fiber material in the subcommissural organ and ventricular area in bile duct ligated rats

Hepatic encephalopathy is a common neuropsychiatric complication of acute and chronic liver failure. Whether brain structures with strategic positions in the interface of blood-brain barriers such as the circumventricular organs are involved in hepatic encephalopathy is not yet established. Among the circumventricular organs, the subcommissural organ secretes a glycoprotein known as Reissner's fiber, which condenses and forms an ever-growing thread-like structure into the cerebrospinal fluid. In the present work we describe the Reissner's fiber material within the subcommissural organ and its serotoninergic innervation in an animal model of chronic hepatic encephalopathy following bile duct ligation in experimental rats. The study involved immunohistochemical techniques with antibodies against Reissner's fiber and 5-hydroxytryptamine (5-HT). Four weeks after surgical bile duct ligation, a significant rise of Reissner's fiber immunoreactivity was observed in all subcommissural organ areas compared with controls. Moreover, significant Reissner's fiber immunoreactive materials within the ependyma and inside the parenchyma close to the ventricular borders were also seen in bile duct ligated rats, but not in control rats. Increased Reissner's fiber material in bile duct ligated rats seems to be related to a reduction of 5-HT innervation of the subcommissural organ, the ventricular borders and the nucleus of origin, the dorsal raphe nucleus. Our data describe alterations of the subcommissural organ/Reissner's fiber material and the subcommissural organ 5-HT innervation probably due to a general 5-HT deficit in bile duct ligated rats.     

Isolated biliary granulocytic sarcoma followed by acute myelogeneous leukemia with multilineage dysplasia: a case report and literature review

Granulocytic sarcoma is a rare extramedullary tumor composed of myeloid progenitor cells. Primary involvement of the biliary tract without evidence of leukemia is exceedingly rare. Here, we report an isolated biliary granulocytic sarcoma in a 30-yr-old man who presented with jaundice, fever, and chill without any evidence of leukemia. However, five months after the diagnosis, he developed acute myelogenous leukemia with multilineage dysplasia and chromosomal abnormality. A rare possibility of biliary granulocytic sarcoma should be considered as a differential diagnosis in patients with obstructive jaundice. A histologic evaluation by aggressive diagnostic intervention is important and may improve prognosis.     

Bile duct injury as a part of diagnostic criteria for liver allograft rejection

The decisive criterium of acute liver allograft rejection was found to be the presence of the diagnostic triad of acute rejection; ie, the presence of portal inflammatory mixed infiltrates, venous endothelialitis (both portal and central), and bile duct injury. On the basis of the presence of each of the components of the diagnostic triad, criteria for the diagnosis of different degrees of acute rejection were developed, particularly focusing attention on a detailed analysis of bile duct injury. Bile duct injury was shown to be an essential part of the histopathologic changes in all grades of acute rejection in the liver allograft, the grade of severity of bile duct injury correlating to a certain extent with the grade of severity of acute rejection. Our analyses have made it evident that bile duct injury, which most probably occurs earlier in the process of acute rejection than endothelialitis, is a more sensitive parameter than endothelialitis in the diagnosis of acute rejection. Furthermore, our analyses have revealed that bile duct injury in acute rejection is likely to be an irreversible process, depending on the number of episodes of acute rejection that previously occurred. On the other hand, it has become clear from our results that bile duct injury must not be considered to be an absolute histopathologic marker of acute rejection; however, it does have to be judged synoptically in connection with the other components of the diagnostic triad and the changes that the triad cause in the hepatic parenchyma. Additional analyses of the grade of severity of cholostases have shown that the cholostases are, to a certain degree, an accompanying phenomenon of the histopathologic changes characterizing acute rejection rather than a histopathologic change that is as significant as the presence of the components of the diagnostic triad.     

Small cell carcinoma of the extrahepatic bile duct: case report and immunohistochemical analysis

A small cell carcinoma of the extrahepatic bile duct in a 75-year-old Japanese man is reported. The patient suffered from obstructive jaundice, and percutaneous transhepatic cholangiography-drainage (PTCD) revealed a massive lesion in the lower common bile duct. Because it was diagnosed as a malignant tumor, pancreaticoduodenectomy was performed. A nodular infiltrating tumor measuring 4.5 x 3.0 x 2.0 cm was located in the intrapancreatic portion of the extrahepatic bile duct. Histologically, the tumor was composed of a dense proliferation of small atypical cells with a little region of high-grade dysplasia in the adjacent epithelium of the common bile duct. Tumor cells were immunoreactive to neuroendocrine markers such as chromogranin A, synaptophysin, CD56, and Leu7. Although carcinoma cells invaded into pancreas and duodenum, there were no histological findings that indicated the carcinoma arose from the mucosa of either the pancreatic duct or duodenum. These results indicated that the tumor was a small cell carcinoma derived from the epithelium of the extrahepatic bile duct; a rare neoplasm with only a few cases reported. A few neuroendocrine cells were recognized in the adjacent epithelium of the extrahepatic bile duct, suggesting that the tumor cells might be derived from them. Using immunohistochemical examination, no p53 abnormality was found. Tumor cells showed positive nuclear staining for p16, while negative for cyclin D1, suggesting that functional retinoblastoma protein (pRB) might be lost in the p16/pRB pathway, as in small cell lung cancer.     

Granulocytic sarcoma as isolated extramedullary relapse after donor lymphocyte infusion in a patient with CML who relapsed after allogeneic bone marrow transplantation: a case report.

Isolated granulocytic sarcoma (GS) has rarely been reported in a patient who underwent allogeneic bone marrow transplantation (BMT) for chronic myelogenous leukemia (CML). We report here a patient who developed an isolated GS after achieving hematologic and cytogenetic remission by donor lymphocyte infusion for the relapse of CML following BMT. The size of GS was slightly decreased after local irradiation of 1,500 cGy without further systemic chemotherapy or immunotherapy. He remained in hematologic and cytogenetic remission without systemic relapse of CML for 8 months. Thereafter, he died of sepsis. The appropriate treatment of GS and impact of its occurrence on prognosis following allogeneic BMT has yet to be determined.     

Hepatitis C and bile duct loss.

AIM: To assess whether bile duct loss is associated with the bile duct damage induced by chronic hepatitis C. METHODS: Sections were examined from 171 liver biopsy specimens from patients with chronic hepatitis C, 98 biopsy specimens from patients with chronic hepatitis B, 25 postmortem specimens from patients with no evidence of liver disease, and 23 patients who underwent protocol liver biopsy at the time of cholecystectomy. RESULTS: The bile duct:portal tract ratio for the hepatitis C group was 0.89, for the hepatitis B group was 0.93 and for the two control groups was 0.96 and 0.90, respectively. The ratio was lower in the hepatitis C group than in the other three. In no case of chronic hepatitis C was the ratio less than 0.60. In the hepatitis C group greater bile duct loss was seen in cirrhotic patients. CONCLUSIONS: Hepatitis C is associated with bile duct loss and this was related to the stage of the disease. However, in the cases studied this did not reach what is generally considered to be significant (that is, greater than 50% of portal tracts lacking bile ducts). This does not preclude a contributory effect of hepatitis C to bile duct loss in the presence of other risk factors, especially in liver transplant recipients.