A case of monoblastic crisis of CML beginning with extramedullary tumor formation in a rib]

A patient with CML showed monoblastic crisis which started with extramedullary tumor formation in a rib before medullary involvement. She was diagnosed as having CML in 1984 at the age of 57. In February 1990, she was admitted to Furukawa City Hospital because of extramedullary blastic crisis beginning at the right 5th rib. At that time, the bone marrow revealed 4.6% blasts. On March 5, after one course of chemotherapy, she was transferred to our hospital for radiotherapy. Hematological findings were WBC 10,100/microliter with 10% blasts, Hb 10.9 g/dl, platelet 3.7 x 10(4)/microliters. Bone marrow aspiration was unsuccessful. The blasts in the peripheral blood were negative for peroxidase and chloroacetate esterase; but positive for naphtylbutyrate esterase. The leukemic cells were positive for CD13, CD33, and had phagocytic activity. Chromosomal analysis revealed 46XX with Ph1 chromosome and some additional anomalies. Southern blot analysis of tumor cells shows BCR rearrangement. These findings suggest that the blasts were immature monocytic cells, and we conclude that this is a rare case of extramedullary monoblastic crisis of CML.     

Megakaryoblastic transformation of chronic myelomonocytic leukemia presenting with severe bone pain

A 77-year-old woman, who had suffered from osteoporosis with compression fractures of vertebrae, was admitted to our hospital because of increasing bone pain. She had anemia and monocytosis, and was diagnosed as chronic myelomonocytic leukemia (CMML). Although chemotherapy was initiated, she died from pneumonia. Autopsy revealed multiple tumors composed of megakaryoblastic cells in her bone marrow and extramedullary organs and, therefore, the pathological diagnosis was made as megakaryoblastic transformation of CMML. Severe bone pain was considered to be a symptom of megakaryoblastic transformation of CMML.     

Primary lung cancer (adenocarcinoma) associated with cardiac sarcoidosis]

A 56-year-old woman who had been given oral prednisolone for iridocyclitis by an ophthalmologist received a diagnosis of pulmonary sarcoidosis on the basis of transbronchial lung biopsy findings, and began receiving therapy at our hospital on an outpatient basis. Chest X-ray films disclosed hilar lymphadenopathy in both lungs. In addition, Holter electrocardiograms detected ventricular premature beat (Lown 4B) and echocardiograms detected reduced left ventricular wall motion with dilatation of the left ventricular chamber. Cardiac sarcoidosis developed in the patient. She was admitted to our hospital because of shortness of breath on exertion. Chest X-ray films on admission disclosed a large nodular heterogeneous mass in the right upper lobe. Histologically, transbronchial lung biopsy specimens of the mass disclosed an adenocarcinoma. Although lung cancer and sarcoidosis are common, their coexistence in the same patient is not. Furthermore, the coexistence of lung cancer with cardiac sarcoidosis, as in this case, is very rare.     

Hypertrophic cranial pachymeningitis in a patient with aplastic anemia

 We report on a 13-year old girl with severe aplastic anemia and hypertrophic cranial pachymeningitis. She was admitted to our hospital with severe headache and vomiting. A computerized tomographic (CT) scan of the brain on the third day of symptoms showed a hyperdense area in the tentorial region. Magnetic resonance imaging (MRI) showed iso-intensity in the same tentorial region in T₁- and T₂-weighted images, and gadolinium enhancement of this region suggested a thickened dura mater. Initially, a diagnosis of subdural or subarachnoid hemorrhage was made. Since her platelet count was low (3000/μl) making the patient a poor-risk candidate for surgery, and the area was limited to the dura mater, conservative therapy, including glycerol administration and platelet transfusion, was carried out. Despite clinical improvement 10 days after admission without specific therapy, the iso-intense region on the left side of the tentorial region remained unchanged on MRI. On the other hand, the iso-intense area on the right side of the tentorial region became hyperdense on T₁-weighted MRI images and was also enhanced by gadolinium. Cerebrospinal fluid findings were normal except for slightly elevated protein at 62 mg/dl. A diagnosis of hypertrophic cranial pachymeningitis of the tentorial dura mater with hemorrhage on the right side was made. Although hypertrophic cranial pachymeningitis is a rare disease, it must be considered in the differential diagnosis of severe headache in a case of aplastic anemia. Received: April 21, 1998 / Accepted: August 28, 1998     

Extramedullary hemopoiesis presenting as a tumor of the posterior mediastinum in a patient with hemolytic anemia

Extramedullary hemopoietic focus is a rare cause of tuberous enlargement of the posterior mediastinum. A 62-year-old man who had been diagnosed as having congenital spherocytic anemia 20 years ago, was admitted to hospital with initial diagnosis of pneumonia. Chest X-ray disclosed inflammatory infiltration in the lower lobe of the right lung and a tumor in the posterior mediastinum. Pneumonia subsided following treatment with antibiotics. Spiral computer tomography with concomitant transthoracic biopsy of the lesion, confirmed the presence of tumor located on the right side of the spinal column, as well as the presence of two minor focci on its opposite side. Cytological examination revealed extramedullary hemopoiesis. Differential diagnosis of tumor in posterior mediastinum, should take into consideration the possibility of extramedullary hemopoietic focci.     

A case of cholangiocarcinoma detected after follow-up for seven years for thorotrast deposition

A 73-year-old former soldier in whom a deposition of thorotrast had been detected 7 years previously was admitted to our hospital because of high fever and epigastric pain. He had been well with standard liver function tests within the normal range until 4 months before admission. Laboratory examination on admission showed marked abnormalities in the liver function tests and an elevated level of CEA. Abdominal ultrasonography and computerized tomography, which had shown no space-occupying lesion in the liver one year earlier, revealed an abnormal mass in the right hepatic lobe. Angiographic examination revealed low vascularity and encasement of the intrahepatic artery. The disease was diagnosed as thorotrast-induced cholangiocarcinoma. Despite chemotherapy, the patient's condition worsened rapidly and he died on the 78th day after admission. At autopsy, the primary tumor in the right hepatic lobe and metastatic nodular tumors throughout the liver were found. The histological diagnosis was cholangiocarcinoma. Thorotrast-induced liver cancers are inclined to grow rapidly, so early diagnosis of liver tumor accompanied by thorotrastosis is very difficult, as in this case. Repeated examinations at frequent intervals are required for early diagnosis.     

Development of cerebellar astrocytoma in a patient with acute myeloid leukemia 8 years after his second bone marrow transplant]

We report a case of cerebellar astrocytoma occurring 8 years after the second bone marrow transplantation (BMT) in 32-year-old man. The patient was admitted to our hospital in December 1997 because of dysarthria and gait disturbance. He had been treated earlier for acute myeloid leukemia (AML M2) with chemotherapy and cranial irradiation followed by allogeneic BMT from a sibling in december 1988. Three months after the first BMT, testicular relapse was observed and followed by systemic relapse. The patient received reinduction therapy and a second successful BMT. He had been well until about 1 month before admission to our hospital. Neurological examination revealed left cerebellar ataxia, and brain magnetic resonance imaging disclosed a left cerebellar tumor. The tumor was surgically resected and a histological diagnosis of cerebellar astrocytoma was made. The patient was further treated by irradiation for residual tumor and discharged without progression of the disease.     

Chronic myelomonocytic leukaemia with t(8;9)(p11;q34) in childhood: an example of the 8p11 myeloproliferative disorder?

We describe the case of a 10-year-old girl with chronic myelomonocytic leukaemia with the chromosomal translocation t(8;9)(p11;q34), who had developed tonsillar lymphoma as extramedullary involvement at the initial presentation. The cytogenetic study of the cells in both bone marrow and tonsils demonstrated t(8;9)(p11;q34), despite no malignant features in the bone marrow specimens. She developed acute leukaemic transformation 8 months after diagnosis during chemotherapy for lymphoma. Although etoposide reduced the number of blasts, t(8;9)(p11;q34)-bearing cells were not eradicated. Complete remission was obtained following an unrelated bone marrow transplantation. The clinical characteristics of this patient are similar to those of the patients with t(8;9)(p11;q34 or q32) or t(8;13)(p11;q11 or q12) reported previously. The unusual progression of the disease might be associated with the presence of t(8;9)(p11;q34), suggesting a part in the 8p11 myeloproliferative syndrome.     

Clinical features of intradural spinal cord metastases in primary lung cancer]

We retrospectively investigated the clinical features of 9 consecutive cases of intradural spinal cord metastasis from primary lung cancer treated at our hospital between April 1999 and March 2002. During those three years, spinal cord metastasis was diagnosed in seven of 49 (14.3%) cases with small cell carcinoma and only two of 284 (0.7%) cases with non-small cell carcinoma. Eight of the 9 cases had concomitant brain metastasis that preceded spinal cord metastasis and had received brain irradiation. The other patient without brain metastasis had also received prophylactic cranial irradiation. The interval from brain irradiation to the diagnosis of spinal cord metastasis ranged from 116 to 708 days (median 183 days). The most common initial symptom was muscle weakness of the lower extremities in five cases. Seven of the patients rapidly developed transverse myelopathy within two weeks. Magnetic resonance imaging (MRI) with contrast enhancement demonstrated intramedullary tumors in seven cases and intradural extramedullary tumors in two cases. Spinal cord metastasis was often multifocal, and in each case lumbar enlargement was commonly involved. Radiation therapy with or without concurrent chemotherapy produced both neurologic improvement and a tumor response shown on MRI in 4 patients. Heightened awareness of the increasing incidence and background risk factors of this unusual complication could lead to earlier diagnosis and more effective treatment for neurologic palliation.     

Leukemic Burkitt's lymphoma with an initial symptom of ocular motor disturbance

A 58-year-old male was admitted to Osaka City University Hospital because of diplopia in May, 1987. Hematological examinations revealed abnormal blastoid cells in his peripheral blood and bone marrow. We found many mitochondria and polysomes in the cytoplasm of the blastoid cells by the electron microscopy. Moreover, left axillary lymph node biopsy specimen disclosed the typical "starry sky" pattern. The blastoid cells in the bone marrow had chromosomal abnormality; 47XY, 8q-, 14q+, 22q-, +mar. Therefore, the diagnosis of Burkitt's lymphoma (leukemic change) was performed. He was treated with chemotherapy, but the blastoid cells resisted many anticancer agents and he died in September 30. On admission left ocular motor disturbance was revealed. Generally, it was reported that meningitis with CNS involvement of lymphoma is accompanied by cranial nerves palsy. However in this case lymphoma cells was not found in the cerebrospinal fluid. The cause of ocular motor disturbance was the adhesion to the medial rectus muscle and compression to the ocular motor nerves of the lymphoma mass.     

Brain metastases of malignant melanoma showing unbalanced whole arm chromosomal translocations der (8; 14) (q10; q10) and der (11; 15) (q10; q10) in a Japanese patient

Since malignant melanoma is a rare malignancy in Japan, little is known about the cytogenetic abnormalities in Japanese patients. We report a case of malignant melanoma showing complex chromosomal abnormalities. A 70-year-old woman was admitted to our hospital because of anorexia, delirium, and right hemiplegia. Cranial CT disclosed several metastatic brain tumors. Multiple subcutaneous and intra-abdominal metastases were also found. A diagnosis of metastatic malignant melanoma was made by biopsy of a subcutaneous tumor. Chromosomal analysis of the tumor cells disclosed complex karyotypic abnormalities including novel unbalanced whole arm translocations der (8; 14) (q10; q10) and der (11; 15) (q10; q10).     

Small cell lung cancer associated with paraneoplastic cerebellar degeneration and Lambert-Eaton myasthenic syndrome]

A 57-year-old man was admitted to our hospital in November 1997 because of dysarthria, progressive ataxia, generalized weakness, and incoordination in both hands. He had been aware of the dysarthria 6 months earlier. Chest roentgenograms and computed tomographic films disclosed a 5 cm x 6 cm mass in the left S3b. The patient was given a diagnosis of small cell lung cancer (T3N2M0, stage IIIA) associated with paraneoplastic cerebellar degeneration (PCD). Three courses of chemotherapy (carboplatin and etoposide) eliminated the tumor and slightly alleviated the PCD symptoms. In March 1998, electromyograms revealed a fall in the single-stimulated M wave and a waxing phenomenon that had not been observed on admission. Anti-P/Q type voltage gated calcium channel antibody was detected in serum samples obtained on admission and after chemotherapy. These findings confirmed an association with Lambert-Eaton myasthenic syndrome. No relapse of the tumor has been observed 15 months after the last course of chemotherapy.     

A case of Ramsey Hunt syndrome with multiple cranial nerve paralysis and acute respiratory failure]

The authors report a 56-year-old woman with Ramsey Hunt syndrome with multiple cranial nerve paralysis and acute respiratory failure. Five days before admission, she experienced right otalgia and right facial pain and consulted an otolaryngologist of our hospital, who diagnosed the illness as acute parotitis and laryngopharyngitis. One day before admission, she experienced mild dyspnea and general fatigue and came to our hospital emergency room. A chest X-ray film revealed no abnormalities but some blisters were observed around her right ear. The next day, her dyspnea became more severe and she was admitted. A chest X-ray film on admission revealed right lower lobe consolidation, and neurological examination disclosed multiple cranial nerve paralysis, i.e., paralysis of the right fifth, seventh, eighth, ninth, tenth, eleventh, twelfth and left tenth cranial nerve. The serum titer of anti-herpes zoster antibody was elevated to 1,024, and the patient was diagnosed as having Ramsey Hunt syndrome with multiple cranial nerve paralysis. Arterial blood gas analysis revealed hypoxemia with hypercapnea, which was considered to be due to aspiration pneumonia and central airway obstruction caused by vocal cord paralysis. Mechanical ventilation was soon instituted and several antibiotics and acyclovir were administered intravenously, with marked effects. Three months after admission, the patient was discharged with no sequelae except mild hoarseness. Patients with herpes zoster oticus, facial nerve paralysis and auditory symptoms are diagnosed as having Ramsey Hunt syndrome. This case was complicated by lower cranial nerve paralysis and acute respiratory failure, which is very rare.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of monocular blindness as the initial presentation of hepatocellular carcinoma with skull metastasis

A 52-year-old man suffering from monocular blindness, with light perception only, was admitted to our hospital. The symptom had begun as low vision and developed rapidly within 3 weeks into monocular blindness in the right eye, with no other systemic manifestations. Imaging examinations revealed multiple hepatocellular carcinomas in the cirrhotic liver, and tumors at the skull base and vertebra. A pathological and immunochemical study of specimens obtained by endoscopic transnasal tumor biopsy and laminectomy revealed them to be metastatic hepatocellular carcinomas (HCCs). Although the patient underwent radiation therapy and chemotherapy, he died 5 months after admission to our hospital. The cranial HCC, involving only the optic canal, may have disturbed the optic nerve in preference to the other cranial nerves. This is the first report of a HCC patient with monocular blindness as the initial presentation of the disease.     

Oxaliplatin‐related sinusoidal obstruction syndrome mimicking metastatic liver tumors

A 40‐year‐old woman who had undergone a curative low anterior resection for advanced rectal cancer was admitted to our hospital. She had been administrated oxaliplatin‐based chemotherapy as postoperative adjuvant chemotherapy. The contrast‐enhanced computed tomography revealed three hypovascular tumors, 3.0, 1.5 and 1.0 cm in diameter, located in the right hepatic lobe. The hepatocyte phase of the gadoxetic acid‐enhanced magnetic resonance imaging demonstrated these lesions as hypointense tumors relative to the surrounding hepatic parenchyma. All these findings of the preoperative imaging modalities were compatible to metastatic liver tumors from the rectal cancer, and right hepatic lobectomy was successfully performed. Histopathologically, the tumors revealed sinusoidal dilation and severe congestion outlined by atrophic hepatocyte trabeculae, which was known as peliosis hepatis. The perisinusoidal space of Disse was extensively dilated and contained many erythrocytes. Taking these findings into account, the hepatic tumors were considered to be the space‐occupying lesions resulting from the sinusoidal obstruction syndrome. We herein report the first case of focal sinusoidal obstruction syndrome mimicking metastatic liver tumors.     

Intrasellar plasmacytoma presenting as a non-functional invasive pituitary macro-adenoma: Case Report & Literature Review

We report an uncommon case of an intrasellar plasmacytoma presenting as a non-functional invasive pituitary macro-adenoma as the first manifestation of multiple myeloma. A 57 year old woman was referred to our department with a presumed diagnosis of a non-functioning pituitary macro-adenoma. She reported a 3 month history of headaches and a 2 week history of sudden onset of right facial numbness. Preoperative endocrine evaluation was remarkable only for a modestly elevated serum prolactin. A magnetic resonance imaging (MRI) scan revealed 3.6 × 5 × 4 cm enhancing homogeneous intrasellar mass with extension into the sphenoid and cavernous sinuses bilaterally; the optic chiasm was not displaced. She underwent transphenoidal surgery of the sellar lesion. The surgical specimen was heavily infiltrated with abnormal plasma cells, which stained almost exclusively for Kappa light chain immunoglobulins. An extensive investigation was undertaken to look for occult myelomatous disease. A diagnosis of multiple myeloma was made 1 month later based on a combination of clinical, pathological and radiologic features. She underwent radiation therapy directed towards the residual sellar tumor, followed by chemotherapy and autologous stem cell transplantation. Review of the world literature revealed only 22 previous reports of patients in whom a solitary plasmacytoma or multiple myeloma first presented as a sellar mass; in all cases mimicking clinically and radiologically a non-functioning invasive pituitary adenoma however with additional cranial nerve involvement. Intrasellar plasma cell tumors are rare tumors which may mimic non-functioning invasive pituitary tumors. The diagnosis should be suspected in patients with well preserved anterior pituitary function and cranial nerve neuropathies in the presence of significant sellar destruction.     

Philadelphia chromosome-negative chronic myelogenous leukemia without breakpoint cluster region rearrangement: a chronic myeloid leukemia with a distinct clinical course

The hallmarks of chronic myelogenous leukemia (CML) include the Philadelphia chromosome (Ph) translocation [t (9;22)(q34;q11)] and consistent molecular genetic aberrations: a break within a restricted 5.8 kb DNA segment, bcr, on chromosome 22q11; transposition of the c-abl protooncogene from chromosome 9q34 to 22q11; and formation of a hybrid bar-abl gene encoding an abnormal 210 Kd bcr-abl protein with augmented tyrosine kinase enzymatic activity. These molecular phenomena may occur even in the absence of cytogenetic evidence of the Ph translocation. They are highly specific and sensitive markers for CML, and are presumed to play a significant role in the pathogenesis of this malignancy. Surprisingly, we have encountered 11 patients who lacked the Ph translocation, bcr rearrangement, and (in the four patients with available mRNA) a bcr-abl message, and yet had a disease phenotype at diagnosis that was a morphologic facsimile of classic chronic phase CML. These patients presented with high white blood cell counts, neutrophilia, occasional basophilia, splenomegaly, and a hypercellular bone marrow with granulocytic hyperplasia and a left shift in myeloid maturation. Despite the striking resemblance between the early stages of bcr-negative and bcr-positive CML, disease progression manifests distinctly in these two disorders. In contrast to the blastic transformation that inevitably complicates bcr-positive CML, the natural history of our 11 Ph-negative, bcr-negative CML patients was characterized by increasing leukemia burden with leukocytosis, pronounced organomegaly, extramedullary infiltrates, and eventual bone marrow failure (anemia and thrombocytopenia) without marked increases in blast cells. Our current observations suggest that a chronic myeloid leukemia process can develop without associated changes in the bcr or c-abl genes. Although the initial phase of this disease is indistinguishable from CML, the presence or absence of molecular markers may aid in the prediction of the clinical course of Ph-negative CML.     

Hypertrophic cardiomyopathy with mid-ventricular obstruction complicated by apical aneurysm appearing as delayed contrast hyperenhancement on magnetic resonance imaging: two case reports

Case 1: A 52-year-old man presented with a chief complaint of palpitation. Diabetes mellitus was pointed out in 1992. Electrocardiography (ECG) revealed left ventricular hypertrophy in 1997. He visited our department in October 1997. Echocardiography showed increased wall thickness at the interventricular septum. The diagnosis was hypertrophic cardiomyopathy. Holter ECG revealed nonsustained ventricular tachycardia in December 1997. After this, he visited our outpatient clinic. Echocardiography indicated ventricular aneurysm in January 2002, so he was hospitalized in March 2002. Case 2: A 64-year-old woman was transferred to our hospital because of chest discomfort and tachycardial attack. She had been treated for hypertension and diabetes mellitus. She was taken to a hospital by ambulance. On admission, ECG showed wide QRS tachycardia. Cardiac magnetic resonance imaging in both patients disclosed almost complete obstruction of the mid-ventricle in the systolic phase on long- and short-axis cine images, and gadolinium delayed imaging revealed contrast hyperenhancement corresponding to an apical ventricular aneurysm on both long- and short-axis images. The final diagnosis was mid-ventricular obstructive hypertrophic cardiomyopathy with apical aneurysm characterized by delayed hyperenhancement on magnetic resonance imaging with gadolinium.     

Spectral karyotyping (SKY) refinement of a complex karyotype with t(20;21) in a Ph-positive CML patient submitted to peripheral blood stem cell transplantation

A patient with a Ph-positive chronic myeloid leukaemia (CML) was submitted to allogeneic peripheral blood stem cell transplantation from an HLA-haploidentical related donor 7 years after the diagnosis. Six months later, he showed a disease relapse while cytogenetic analysis displayed a complex karyotype. To characterise the chromosomal rearrangements spectral karyotype (SKY) analysis was used. This redefined all chromosome rearrangements and revealed a t(20;21)(q11;q22). FISH analysis with a specific probe for the AML1 gene disclosed disruption of this gene which was partially translocated on to the long arm of chromosome 20. It is likely that this rearrangement, unusual for CML, was implicated in the disease evolution towards blastic crisis (BC).     

A case of adult T cell leukemia complicated by proliferative synovitis

A 60-year-old woman was admitted to our hospital with symmetrical arthritis of the knees. During the 2 years preceding admission, she had experienced recurrent arthritis. A histological examination of her synovial tissue showed prominent villous proliferation of the synovial cells, prominent vascularity throughout and an inflammatory infiltrate composed of abnormal mononuclear cells. Three months later, she developed fever, skin eruptions, lymphadenopathy and hepatosplenomegaly. She also had hypercalcemia and there was abnormal lymphocytosis in her blood smears. She was diagnosed as having adult T cell leukemia. Parenteral chemotherapy treatment with adriamycin and cyclophosphamide gave remission of all the manifestations of disease, including arthritis. Her leukemia recurred, however, and she died 6 months after the diagnosis was made.