Hereditary hemorrhagic telangiectasia with malignant lymphoma. An autopsy case

A 60-year-old Japanese woman was diagnosed at autopsy as having had hereditary hemorrhagic telangiectasia (HHT) associated with systemic hemangiomas. In her reproduction period, premenstrual epistaxis frequently occurred. At the age of 60, the patient died of malignant lymphoma. At autopsy, multiple telangiectatic spots were noted on the face, limbs and trunk. The paraaortic lymph nodes, which were enlarged and irregularly conglomerated, were histologically diagnosed as malignant lymphoma of the diffuse large cell type. Submucosal telangiectatic lesions were found in the gastrointestinal system from the oral cavity to the rectum. Cavernous hemangiomas were present in various visceral organs including the liver, spleen, small and large intestines, rectum, appendix, uterus, and jejunal and colonic mesenteries. There was an arteriovenous fistula in the left lung. Examination of her family pedigree showed that the patient had an autosomal dominant trait of inheritance. The pathogenesis of the systemic visceral hemangiomas observed in this patient was considered to be similar to that of harmartoma.     

L?ffler's endocarditis. Occurrence with malignant lymphoma with a high content of epithelioid histiocytes ('Lennert's lymphoma')

In a patient who had malignant lymphoma with a high content of epithelioid histiocytes (so-called Lennert's lymphoma), L?ffler's endocarditis developed 18 months after her diagnosis of lymphoreticular malignant neoplasm. She died of refractory congestive heart failure, and an autopsy showed the typical gross and microscopic findings of L?ffler's endocarditis. To our knowledge, this is the first reported association of these two diseases. We noted nine autopsy cases in the literature of L?ffler's endocarditis occurring in patients with lymphoreticular malignant neoplasms (acute lymphoblastic leukemia and lymphoma). L?ffler's endocarditis with eosinophilia may be a relatively uncommon but significant complication in patients with malignant lymphoproliferative disorders. The peripheral blood eosinophilia probably represents a reactive response to tumor antigen.     

Aspergillus fumigatus fungaemia and myocarditis in a patient with acquired immunodeficiency syndrome.

Necrotizing myocarditis due to Aspergillus fumigatus was a contributory cause of death in a patient with acquired immunodeficiency syndrome and non-Hodgkin lymphoblastic malignant lymphoma of the Burkitt type. A transient remission of the lymphoma had been obtained by cytostatic treatment. A. fumigatus was isolated from blood two weeks before death, but myocarditis was not diagnosed until autopsy.     

T-cell lymphoma after heart transplantation

A 26-year-old woman who had undergone orthotopic heart transplantation because of dilative cardiomyopathy received a triple-drug immunosuppressive regimen (cyclosporine A, azathioprine, and prednisolone). During her relatively frequent episodes of acute rejection, she was treated with methylprednisolone and repeated application of ATG. A short time before the patient's death, a fine-needle aspiration of the liver revealed the cytologic diagnosis of a malignant pleomorphic medium-size cell non-Hodgkin's lymphoma of a higher grade of malignancy. Immunosuppression was reduced, and the patient died in cardiogenic shock related to a histologically confirmed episode of severe acute rejection 264 days after the transplantation. On autopsy, the malignant lymphoma previously diagnosed by fine-needle aspiration cytology was found to be present in the liver as the only extranodal localization. The immunohistologic analysis of the immunophenotype specified the lymphomatous neoplasia as a T-cell lymphoma. The particular importance of this case is that it is, to our knowledge, the third case of proven T-cell lymphoma following organ grafting documented in the literature and the first case described in a cardiac allograft recipient.     

Complicating systemic amyloidosis in dystrophic epidermolysis bullosa, recessive type

An autopsy case of dystrophic epidermolysis bullosa, recessive type, complicated by systemic secondary amyloidosis is described. The patient had developed multiple bullous lesions and erosions from birth, followed by repeated infection. At autopsy, chronic persistent inflammation was observed in the skin and in various visceral organs, accompanied by systemic amyloidosis. By the peroxidase-antiperoxidase (PAP) method, amyloid deposits stained positively for anti-AA-protein antiserum. In the present case, we concluded that the systemic amyloidosis was of the AA type, and developed secondarily to the chronic persistent inflammation in the prolonged course of dystrophic epidermolysis bullosa, recessive type.     

Seroma-associated primary anaplastic large-cell lymphoma adjacent to breast implants: an indolent T-cell lymphoproliferative disorder.

Non-Hodgkin lymphomas of the breast are rare, encompassing approximately 0.04-0.5% of all malignant breast tumors, and the vast majority are B-cell lymphomas. In contrast, lymphomas of T-cell phenotype have been rarely reported and some of these have been in close proximity to a breast implant. In our consultation practice, we have identified four patients with primary T-cell anaplastic large-cell lymphoma presenting adjacent to silicone or saline breast implants. All patients presented with seroma and neoplastic cells were identified in suspension in the serous fluid without solid tissue invasion. Three patients had no evidence of systemic disease (stage 1E), and one patient was not staged. The mean age of the patients was 46 years (range, 34-59 years). In all patients, the neoplastic cells had a T-cell phenotype, expressed CD30, cytotoxic granule-associated proteins, EMA and clusterin, and were anaplastic lymphoma kinase-1-negative. Clonal T-cell receptor gamma-chain gene rearrangements were identified in three patients. All patients underwent capsulectomy with removal of the implant. One patient subsequently received chemotherapy and radiation therapy, and another was treated with radiation alone. The third patient received no further therapy and the fourth patient has been recently diagnosed. After a mean time of 13 months (range, 9-20 months), all three patients with follow-up were alive and well without any recurrence or systemic disease. Although the follow-up time was relatively short, our series and other reported cases suggest that primary anaplastic large-cell lymphoma adjacent to breast implants is an indolent T-cell lymphoproliferative disorder.     

Mucosa-associated lymphoid tissue lymphoma coexisting with epithelioid granulomas in the stomach of a patient with systemic sarcoidosis

Malignant lymphoma arising in the stomach of a 23-year-old Japanem man with systemic sarcoldosis is presented. The patient was followed because of systemic sarcoidosis involving the lungs, eyes, and lymph nodes. Biopsy specimens from the stomach were repeated because of recurrent eplgastraigia and multiple ulcerations. Some of the specimens revealed epithelloid granuiomas with no caseous necrosis, which confirmed gastric involvement of sarcoidosis. Three years after the initial diagnosis, biopsy specimens taken from the stomach were diagnosed as malignant lymphoma of the large cell type. The resected stomach revealed muiticentric mucosa-associated type malignant lymphoma of low-grade B cell type, with foci of high-grade transformation coexisting with numerous epithelioid granulomas with no caseous necrosis. Epithelloid granulomas were observed in all the respected lymph nodes, liver, and appendix, which had been obtained at operation, whereas malignant lymphoma was limited to the stomach. Hellcobacter pylori (H. pylori ) infection was also observed in the stomach. Consequently, the present report is a rare case of coexistence of malignant lymphoma and involvement of sarcoidosis in the stomach. Both H. pylori infection and active sarcoid noduies may play a role in the development of malignant lymphoma, although the exact mechanism remains undear.     

Immunoblastic sarcoma

A systemic, malignant disorder of immunoblasts has been reported to occur as a late transition phase of immunoblastic lymphadenopathy in an older population. With a background of polyclonal gammopathy, drug sensitivity, lupus erythematosus or rheumatoid arthritis, there may develop a progressive "cloning out" of monomorphous immunoblasts to form immunoblastic sarcoma. Recently, a 17-year-old, postpartum girl without these bizarre hypersensitivity phenomena developed a rapidly fatal, systemically malignant process with severe clinical complications. No historical incitent was identified. The pregnancy had been uneventful and birth had produced a thriving, viable infant. This case may represent the youngest patient with primary, malignant immunoblastic disease occurring in the absence of a "hypersensitivity" state. A brief discussion of the clinical situation, management, and autopsy findings, is presented. Basic morphologic criteria for proper differentiation of malignant immunoblastic problems, lymphoma, and Hodgkin's disease are discussed.     

Primary malignant lymphoma of the rectum with diagnostic problems. Report of two cases with an analysis of gene rearrangement.

We present two similar cases of rectal B-cell lymphoma with diagnostic problems. Grossly, both tumors appeared as a well demarcated polypoid mass with eroded mucosa. In spite of their histologic resemblance to reactive lymphoid hyperplasia, including the presence of lymph follicles, fibrosis and polyclonal plasma cells, both cases were diagnosed as malignant lymphoma of low-grade malignancy because of the full-thickness involvement of the rectum with diffusely infiltrated small or medium-sized lymphoid cells showing rare mitoses. In one case, clonal proliferation of differentiated B cells was demonstrated by analysis of gene rearrangement. Therapeutic problems related to low-grade malignant lymphoma in the rectum are also discussed.     

A case of disseminated Phialophora parasitica infection

The numbers and kinds of fungi that are known to cause human mycoses have increased greatly in the past decade. We report the first case (to our knowledge) of disseminated Phialophora parasitica infection. The patient, a 92-year-old woman, had known chronic subcutaneous infection with P parasitica. The systemic nature of her disease was diagnosed at autopsy, when the organism was identified in cultures obtained from a thrombus within an abdominal aortic aneurysm and was also histologically demonstrated within sections obtained from the aneurysm wall.     

An autopsy case of chronic progressive external ophthalmoplegia with renal insufficiency

An autopsy of a 44-year-old Japanese woman with mitochondrial cytopathy confirmed the presence of chronic progressive external ophthalmoplegia (CPEO). Immunohistochemistry using antimitochondrial antibody was performed to observe the ultrastructure of the skeletal muscle and renal tissues. The patient was born of consanguineous parents, developed normally, and was of average intelligence. At 22 years of age, the patient noticed hearing loss, and subsequently, over time, developed a progressive generalized muscle weakness, which included limitation of eye movement and ptosis. At age 41, a muscle biopsy was performed using the modified Gomori trichrome method and demonstrated the presence of ragged red fibers. After the evaluation of her results in conjunction with her clinical course, she was diagnosed with CPEO. Renal insufficiency was discovered at age 30, and the patient died at the age of 44 of respiratory failure caused by respiratory muscle weakness and pneumonia. The autopsy revealed fiber size variation within the skeletal muscle, and an antimitochondrial antibody analysis demonstrated the accumulation of mitochondria between the bundles of myofibrils, as well as in subsarcolemmal locations. Ultrastructurally, abnormal mitochondria with disoriented cristae and paracrystalline inclusions were seen. Although no remarkable histological changes were noted in the kidneys, tubular epithelial cells exhibited accumulated abnormal mitochondria, similar to those seen in the skeletal muscle. Because mitochondrial diseases can affect other energy-dependent organs in addition to the skeletal muscle, immunohistochemical examina-tions employing an antimitochondrial antibody are useful for obtaining further ultrastructural observations that can assist in making a distinct diagnosis of this systemic disorder.     

Primary Malignant Lymphoma of the Rectum with Diagnostic Problems

We present two similar cases of rectal B-cell lymphoma with diagnostic problems. Grossly, both tumors appeared as a well demarcated polypoid mass with eroded mucosa. In spite of their histologic resemblance to reactive lymphoid hyperplasia, Including the presence of lymph follicles, fibrosis and polyclonal plasma cells, both cases were diagnosed as malignant lymphoma of low-grade malignancy because of the full-thickness involvement of the rectum with diffusely infiltrated small or medium-sized lymphoid cells showing rare mitoses. In one case, clonal proliferation of differentiated B cells was demonstrated by analysis of gene rearrangement. Therapeutic problems related to low-grade malignant lymphoma in the rectum are also discussed. Acta Pathol Jpn 41: 623-628, 1991.     

November 2002: a 72-year-old woman with a pineal gland mass

The November 2002 COM. A 72-year-old immunocompetent woman presented with recent confusion, memory loss, visual and a gait disturbance. MRI scans demonstrated a T2 hypointense, gadolinium enhancing mass in her pineal region. A whole body CT scan identified a large retroperitoneal mass and significant lymphadenopathy. She underwent a biopsy of the pineal lesion. The intraoperative smear contained discohesive, basophilic malignant cells of moderate size that had only scant cytoplasm, an increased nuclear-to-cytoplasmic ratio and irregular, hyperchromatic nuclei containing prominent nucleoli. Mitotic figures, apoptotic and lymphoglandular bodies were frequent. Histologic examination showed malignant cells infiltrating and almost completely replacing the residual pineal gland. The tumor cells immunoreacted with LCA and CD-20. Scattered CD3 and UCHL-1 positive cells were also present. The diagnosis was stage IV, high grade, large B-cell lymphoma involving the pineal gland and retroperitoneum. Four cycles of systemic chemotherapy significantly reduced the patient's retroperitoneal mass. However, a repeat head MRI scan continued to show gadolinium-enhancement in the pineal region, now with extension into contiguous brain parenchyma and the subependymal region. The patient died 4 months after presentation. At autopsy, the lymphoma encased the pineal region and disseminated along the ventricular walls and into the subarachnoid spread. Pineal-region tumors are rare in the elderly population, and although unusual, lymphomas should be considered in this context. The behavior of this circumventricular organ lymphoma was comparable to both peripheral and primary central nervous system lymphomas.     

MALIGNANT "RITON" TUMOR WITH METASTATIC HEMANGIOPERICYTOMA IN A PATIENT ASSOCIATED WITH VON RECKLINGHAUSEN'S DISEASE

An autopsy case of malignant schwannoma in a 31-year-old female associated with von Recklinghausen's disease with unusual elements is reported. The patient who was diagnosed as von Recklinghausen's disease from a biopsy specimen of a subcutaneous tumor in her shoulder and multiple café au lait spots in her chest and back, complained of gradual increase in pain in her lower abdomen. A large mass measuring about 18 cm in diameter was located in her left retroperitoneum. Malignant schwannoma associated with von Recklinghausen's disease was indicated by the cellularity of the tumor, intersecting bundles of spindle cells, alternating cellular and less cellular myxoid areas in the peripheral portion of the tumor, whereas a large part of the tumor had a hemangiopericytoma-like arrangement with gaping blood vessels. In addition, however, foci of rhabdomyosarcomatous differentiation and of angiosarcomatous components were found in some areas of this tumor. Moreover, intravascular schwannian growth, which was presumably related to von Recklinghausen's disease, was observed in the heart and thyroid. This tumor should be classified as a malignant triton tumor because of the presence of rhabdomyoblasts.     

Primary Malignant Lymphoma of The Breast With a Review of 73 Cases among Japanese Subjects

We report a case of a 71-year-old female with primary malignant lymphoma of the breast. The patient noticed a lump in the right breast approximately six years prior to consultation to the Surgical Department because of a rapid growth of the lump, and had no other tumors noticed throughout the body during that period. Histology proved the case to be a “reticulum cell sarcoma” (large cell type) producing IgM in the tumor cells, idstead of a breast carcinoma as clinically diagnosed. At the same time, a total of 73 cases of mammary malignant lymphoma among Japanese subjects were reviewed. The criteria for primary or secondary malignant lymphoma of the breast, and histological diagnosis and pathogenesis of the primary breast malignant lymphoma were discussed.     

Pulmonary lymphomatoid granulomatosis with immunodeficiency terminating as malignant lymphoma

Lymphomatoid granulomatosis was diagnosed in a 60-yr-old woman 2 yr after presentation with a multi-system disorder resembling sarcoidosis. Five months later autopsy revealed malignant lymphoma. Large aggregates of intracytoplasmic tubular structures resembling nucleocapsid material of the paramyxovirus group were found within cells of lymphoma deposits in the liver. Sequential immunological studies over more than 2 years demonstrated a relatively stable T-cell deficiency associated with variable B-cell dysfunction. The latter was characterized by the production of immunoglobulins of restricted electrophoretic mobility. Intermittent hypercalcaemia was associated with increases in serum IgG and appeared to be due to the presence of Ca-binding paraproteins. It is suggested that lymphomatoid granulomatosis may be a pre-malignant lymphoproliferation, with immune deficiency as a predisposing cause. The pattern of immunological abnormalities suggests that the lymphoma may have been due to B-cell malignant transformation.     

Primary malignant lymphoma of the breast. With a review of 73 cases among Japanese subjects

We report a case of a 71-year-old female with primary malignant lymphoma of the breast. The patient noticed a lump in the right breast approximately six years prior to consultation to the Surgical Department because of a rapid growth of the lump, and had no other tumors noticed throughout the body during that period. Histology proved the case to be a "reticulum cell sarcoma" (large cell type) producing IgM in the tumor cells, instead of a breast carcinoma as clinically diagnosed. At the same time, a total of 73 cases of mammary malignant lymphoma among Japanese subjects were reviewed. The criteria for primary or secondary malignant lymphoma of the breast, and histological diagnosis and pathogenesis of the primary breast malignant lymphoma were discussed.     

Malignant "triton" tumor with metastatic hemangiopericytoma in a patient associated with von Recklinghausen's disease

An autopsy case of malignant schwannoma in a 31-year-old female associated with von Recklinghausen's disease with unusual elements is reported. The patient who was diagnosed as von Recklinghausen's disease from a biopsy specimen of a subcutaneous tumor in her shoulder and multiple café au lait spots in her chest and back, complained of gradual increase in pain in her lower abdomen. A large mass measuring about 18 cm in diameter was located in her left retroperitoneum. Malignant schwannoma associated with von Recklinghausen's disease was indicated by the cellularity of the tumor, intersecting bundles of spindle cells, alternating cellular and less cellular myxoid areas in the peripheral portion of the tumor, whereas a large part of the tumor had a hemangiopericytoma-like arrangement with gaping blood vessels. In addition, however, foci of rhabdomyosarcomatous differentiation and of angiosarcomatous components were found in some areas of this tumor. Moreover, intravascular schwannian growth, which was presumably related to von Recklinghausen's disease, was observed in the heart and thyroid. This tumor should be classified as a malignant triton tumor because of the presence of rhabdomyoblasts.     

B-chronic lymphocytic leukemia showed triple transformation,to diffuse large B cell,CD20-negative,and T-cell neoplasm during ofatumumab treatment: a case report

Background

Chronic lymphocytic leukemia (CLL) is a mature lymphoid neoplasm currently categorized as an indolent type of malignant lymphoma. CLL progresses slowly over years, but it eventually transforms to a more aggressive lymphoma such as the diffuse large B-cell (DLBCL) type, also known as Richter’s syndrome.

Case presentation

We treated a 69-year-old Japanese male who was histologically diagnosed with Richter’s syndrome after 6 years of CLL. His lymphadenopathy had systemically progressed for years, with lymphocyte counts of less than 10,000 cells/μL and a disease status of Rai classification stage I and Binet classification B. He had high fever and hepatosplenomegaly upon Richter’s transformation. The patient was treated with ofatumumab for refractory CLL, which relieved his febrile lymphadenopathy. He received a total of 11 ofatumumab courses and achieved partial remission. On the day of the 12th course of ofatumumab, his disease relapsed with febrile lymphadenopathy. Computed tomography revealed multiple liver masses and systemic lymphadenopathy, while a liver biopsy confirmed T-cell lymphoma. Concomitantly, CD20-lacking CLL cells were detected in his peripheral blood and bone marrow, and pathological examination of his left cervical lymph node biopsy showed CD20-positive DLBCL. The final diagnosis was three different types of lymphoma pathologies: (1) CD20-positive DLBCL of the lymph nodes, (2) CD20-lacking CLL of the peripheral blood and bone marrow, and (3) peripheral T-cell lymphoma (PTCL) of the liver. He received intravenous and oral dexamethasone therapy as palliative care. He died because of the rapid progression of abdominal masses 2 months after the diagnosis of triple transformation CLL. An autopsy revealed aggressive PTCL with aggressive systemic involvement of the liver, spleen, gall bladder, pericardium, bone marrow, and mediastinal–paraaortic–intraceliac lymph nodes. T-cell receptor study of an autopsy specimen supported the diagnosis of PTCL that spread to the intraceliac organs and lymph nodes. We concluded that his pathogenicity progressed to a mixture of triple lymphoma as a result of double malignant transformations, which included PTCL from CLL, CD20-negative CLL, and CD20-positive DLBCL by Richter’s transformation.

Conclusions

Our case provides information on the biology of CLL, to transform from a low-grade chemosensitive status to a malignant chemoresistant status.

     

Epstein-Barr virus-infected malignant T/NK-cell lymphoma in a patient with hypersensitivity to mosquito bites

We report an autopsy case of Epstein-Barr virus (EBV)-infected malignant lymphoma in a young male who had hypersensitivity to mosquito bites. The autopsy revealed multiple confluent lymphoma lesions in the lungs, and on the right leg irregular-shaped skin ulcers were seen. The left pleural effusion also contained a large number of lymphoma cells. The lymphoma cells were determined as T/NK-cell type cells by immunohistochemistry. EBV DNA was detected most intensively in the lungs and EBV-encoded small RNAs-positive lymphoma cells were also observed in the lungs at a high frequency. EBV latent membrane protein-1 expression and a high Ki-67 labeling indices were noted in the lymphoma cells of the lung lesions. These findings indicate that the development of the malignant lymphoma was associated with the proliferation of EBV-infected lymphoma cells, and the cells that infiltrated the whole the body, especially the lungs, caused the patient's death.