Random Skin Biopsy Research Articles

Malignant lymphoma presenting as inflammation of unknown origin

We classified underlying diseases presenting as inflammation of unknown origin in division of rheumatic diseases. On the other hand, patients with malignant lymphoma (ML) varying in cause and symptoms are often admitted to our Rheumatology Division as cases of malignant disease presenting with fever of unknown origin. Clinical records over 5 years were reviewed for 246 cases of undiagnosed inflammatory diseases at hospitalization. The 246 patients included 76 patients with infection, 116 with rheumatic disease, 8 with solid cancer, 9 with drug-induced fever, 10 with other disorders, and 27 with suspected ML. Of theses, malignant lymphoma (ML) was diagnosed in 20 patients (5 Mature T-cell and NK-cell neoplasms, 3 Hodgkin lymphomas, and 12 Mature B cell neoplasms including 5 Intravascular large B-cell lymphoma (IVLBCL)). The reasons for hospitalization were underlying collagen disease in 6 patients, medical workup for fever of unknown origin in 8 patients, and symptoms suggestive of collagen disease in 6. Nearly all of these patients presented with fever and other B symptoms, frequently with concurrent hypoxemia and hemophagocytic syndrome in IVLBCL. For diagnostic purposes, biopsy sites were determined by 18 fluorodexyglucose-positron emission tomography and computed tomography (FDG-PET/CT) in 13 patients, and findings on random skin biopsies were diagnostic in 3 of 5 patients with IVLBCL. Laboratory data on patients with B-cell lymphoma or peripheral T-cell lymphoma revealed tendencies for thrombocytopenia, elevated serum LDH, and increased soluble interleukin-2 receptor (sIL-2R). High serum ferritin values were more frequent in IVLBCL than in other B-cell lymphomas. ML ranked first among causes of inflammation of unknown origin at the division of Rheumatic Diseases, and FDG-PET/CT proved to be useful for biopsy site selection. IVLBCL was not uncommon, and our results show the usefulness of clinical features and random skin biopsies for rapid diagnosis.

副腎皮質ステロイドが奏功した脳アミロイドアンギオパチー関連白質脳症の1例

An 86-year-old woman was admitted following generalized seizure. Postictally she showed disturbance of consciousness, right hemiparesis, and right spatial neglect. Brain fluid attenuated inversion recovery (FLAIR) imaging demonstrated mainly left-sided, but asymmetrical, subcortical white matter lesions. On the second day, level of consciousness improved, along with right hemiparesis and right spatial neglect. Electroencephalography displayed mainly α waves and sporadic θ waves without sharp waves. One week later, however, the patient again experienced somnolence and right hemiparesis. FLAIR revealed day-by-day enlargement of white matter lesions. The possibilities of hypoglycemia, hyperammonemia, hypothyroidism, Hashimoto encephalopathy, collagen disease, antineutrophil cytoplasmic antibody-related angiitis, and infection were excluded based on the results of blood biochemistry and cerebrospinal fluid. We initially suspected intravascular lymphoma, so random skin biopsy was performed, but the results were negative. We then suspected cerebral amyloid angiopathy because of the presence of dementia and multiple microbleeds on T(2)* weighted magnetic resonance imaging. Cerebral biopsy revealed amyloid deposition in cortical arterioles and CD3-positive T cells in the perivascular space. Cerebral amyloid angiopathy-related leukodystrophy was therefore diagnosed and immunosuppressive treatment was started. After 14 days of treatment, clinical symptoms and results of FLAIR imaging were significantly improved. When patients display asymmetrical subcortical white matter lesions with microbleeds on T(2)* weighted imaging, amyloid angiopathy-related inflammation should be considered.

Progressive multifocal cerebral infarction from intravascular large B cell lymphoma presenting in a man: a case report

IntroductionIntravascular lymphoma is rare, and may present as ischemic stroke. Diagnosis is difficult due to the non-specific presentation and lack of lymphadenopathy, thus leading to frequent instances of autopsy-proven diagnosis. To the best of our knowledge, this is the first report of progressive stroke from intravascular lymphoma diagnosed antemortem by random skin biopsy.Case presentationA 42-year-old Thai man presented to our hospital with progressive multifocal cerebral infarction. Despite taking aspirin (300 mg/day), his neurological symptoms worsened. During admission, he developed an unexplained fever and hypoxemia. Magnetic resonance angiography clearly showed patency of all cerebral arteries including the internal carotid and vertebrobasilar arteries. Echocardiography, an antiphospholipid antibody test, cerebrospinal fluid cytology and a bone marrow study were normal. Other laboratory test results showed an elevated lactate dehydrogenase level, nephrotic range proteinuria (3.91 g/day), hypoalbuminemia (1.9 g/dL), a very low high-density lipoprotein level (7 mg/dL) and hypertriglyceridemia (353 mg/dL). Because of suspected vasculitis, pulse methylprednisolone was given with transiently minimal improvement. A random skin biopsy from both thighs revealed intravascular large B cell lymphoma. Chemotherapy was not given due to our patient having ventilator associated pneumonia. He died 10 days after the definite diagnosis was established.ConclusionOne etiology of stroke is intravascular lymphoma, in which random skin biopsy can be helpful for antemortem diagnosis.

A Patient with a Six-month History of Fever of Unknown Origin, Followed by Various Manifestations of the Central Nervous System, Finally Diagnosed as Having Intravascular Lymphoma by Random Skin Biopsy.

A Patient with a Six-month History of Fever of Unknown Origin, Followed by Various Manifestations of the Central Nervous System, Finally Diagnosed as Having Intravascular Lymphoma by Random Skin Biopsy.

Early diagnosis of recurrent diffuse large B-cell lymphoma showing intravascular lymphoma by random skin biopsy

A 66-year-old man was admitted to our hospital presenting 2 weeks' history of fever of unknown origin with elevated levels of lactate dehydrogenase and C-reactive protein. Six years before this episode, he had developed diffuse large B-cell lymphoma, which had been successfully treated with chemoradiation. While recurrence of diffuse large B-cell lymphoma was suspected, there was neither lymphadenopathy nor tumor formation by the imaging study. Random biopsy from normal-appearing abdominal skin showed extensive infiltration of CD20(+), CD79a(+), CD3(-) atypical lymphoid cells in the lumen of vessels in subcutaneous tissues. These findings led us to the diagnosis of intravascular B-cell lymphoma. Following rituximab plus cyclophosphamide, adriamycin, vincristine and prednisolone therapy, high fever subsided, and lactate dehydrogenase and C-reactive protein levels returned to the normal range. In conclusion, random skin biopsy is useful for the early diagnosis of intravascular B-cell lymphoma.

Intravascular large B‐cell lymphoma cells in the bone marrow smear preparation

Intravascular large B-cell lymphoma (IVLBCL) is a subtype of extranodal large B-cell lymphoma characterized by the growth of lymphoma cells only within the lumina of small vessels in the various organs (Swerdlow et al, 2008). Because of its rarity and its variety of the clinical presentations, the definite diagnosis of IVLBCL often requires long time with repeated applications of biopsy on the various organs. Bone marrow is demonstrated to be one of the affected organs (Masaki et al, 2009) and a diagnostic site in IVLBCL (Murase et al, 2007). However, the detection of lymphoma cells within the lumina of small vessels and/or sinuses in the bone marrow biopsy specimen is not necessarily guaranteed because, at least in part, the quantity of specimen yield by a single painful procedure is not large. We show characteristic morphology of IVLBCL cells in the May-Grünwald Giemsa (MG)-stained bone marrow smear preparation, which could be one of the useful features for the diagnosis of IVLBCL. From February 2006 through April 2010, 11 patients were clinically diagnosed as having intravascular lymphoma in our institute. In the retrospective analysis, five out of the 11 patients fulfilled the following presentations for the definite diagnosis of IVLBCL: (i) the proposed clinical diagnostic criteria for IVLBCL (Masaki et al, 2009), (ii) the characteristic accumulation of 18[F]-fluorodeoxyglucose (FDG) in the positron emission tomography (PET)/computed tomography (CT) (Miura & Tsudo, 2010) and (iii) the existence of atypical lymphoid cells within the lumina of small vessels in the biopsy specimens (Asada et al, 2007). In the examination of MG-stained bone marrow smear preparation, four out of the five patients presented with an involvement of IVLBCL cells (Table I). Among the four patients, the IVLBCL cells demonstrated similar unique morphological features in the three patients (Fig 1, Case #2, #3 and #5). The IVLBCL cells are large-sized cells with basophilic cytoplasm, vacuoles in the cytoplasm, not fine chromatin in the nuclei. Cell aggregates were found in two out of the three patients (Fig 1, Case #2 and #5). May-Grünwald Giemsa (MG)-stained bone marrow smear preparation of three intravascular large B-cell lymphoma (IVLBCL) patients. (Case #2) 64-year-old man. (Case #3) 74-year-old woman. (Case #5) 57-year-old woman. All three patients fulfilled the proposed clinical diagnostic criteria of IVLBCL, showed the characteristic features in 18[F]-PET/CT examination and existence of atypical lymphoma cells within the lumina of small vessels in the random skin biopsy specimens. The IVLBCL cells demonstrated a similar unique morphological feature in all three patients showing large-sized cells with basophilic cytoplasm, vacuoles in the cytoplasm, not fine chromatin in the nuclei. Cell aggregates were found in two out of the three patients (Case #2 and #5). Bone marrow is one of the initial sites of histological examination for the diagnosis of lymphoma. Biopsy specimen of bone marrow is reported to be useful for the diagnosis of IVLBCL (Masaki et al, 2009). In our retrospective analysis, however, the existence of lymphoma cells within the lumina of small vessels and/or sinuses in the hematoxyline-eosin (HE)-stained bone marrow biopsy specimen was confirmed in none of the patients with definite diagnosis of IVLBCL (Table I). Regarding the discrepancy between the previous reports and our results, we would speculate that there are methodological differences in detection of lymphoma cells such as the quantity of biopsy specimen yield, the number of biopsy specimen sections reviewed and the use of immunohistochemical analysis. On the other hand, the preparation of MG-stained smear of bone marrow aspirate is a relatively uniform procedure. In our analysis, the involvement of IVLBCL cells in the bone marrow smear was observed in four out of the five patients in which multiple accumulations of FDG in the bones were confirmed in the PET/CT examination (Table I). Three out of the four patients presented with IVLBCL cells with a similar unique characteristic morphology in the MG-stained bone marrow smear preparation (Fig 1). We would like to suggest that lymphoma cells shown here are one of the patterns of IVLBCL cells and that further investigations including 18[F]-FDG-PET/CT and/or random skin biopsy should be applied actively to make an early diagnosis of IVLBCL for such patients.

Massive Pleural Effusions and Anasarca After Allogeneic Hematopoietic Cell Transplantation.

AbstractAbstract 4556A 37 year old male with T cell acute lymphoblastic leukemia with normal cytogenetics 46XY in second complete remission (CR2) after 8 cycles of HyperCVAD and 4 cycles of salvage nelarabine underwent myeloablative conditioning with cyclophosphamide TBI for a matched related donor allogeneic stem cell transplant from his brother. His day+100 bone marrow biopsy showed CR2 and was 100% donor. His post transplant course was unremarkable until he relapsed d+162. The immunosuppression was tapered off rapidly and 2 cycles of nelarabine and a donor lymphocyte infusion (1×107 CD3 cells/kg) were completed by d+254 and CR3 was achieved. He did well until d+608 when he presented with a month long history of dyspnea and recurrent bilateral large pleural effusions (despite multiple large volume thoracenteses) and anasarca including facial edema. He had gained 15 kilograms in 2 weeks. He had no fever, skin rash, sicca syndrome or lichen planus. Chest and abdomen CT showed massive bilateral pleural effusions, but no lung infiltrate, pericardial effusion or ascites or lymphadenopathy. The complete blood count, renal function and liver function tests were normal and there was normal hepatopedal flow in the main portal vein and its branches. The echocardiogram showed a left ventricular ejection fraction of 60% (normal) and there were no vegetations. The serum ANA, anti-Ro and anti-La were negative. The bone marrow biopsy showed no evidence of relapse of T cell ALL. The peripheral blood STR was 100% donor. The pleural fluid was transudative and cytology showed no malignancy. Pleural fluid flow cytometry showed no CD20+ B cells but did show polyclonal T cells with a CD4:CD8 ratio of 0.22. The pleural biopsy showed reactive mesothelial cells with mixed acute and chronic inflammation and no malignancy. Ebstein Barr virus in-situ hybridization and HHV-8 immunohistochemistry was negative on the pleural biopsy. All bacterial, fungal and viral (including CMV, EBV, HSV, adenovirus, VZV, HIV, BK) of the blood, urine and pleural fluid were unremarkable. A random skin biopsy of the forearm showed scleroderma. Methylprednisolone 2 mg/kg iv daily and therapeutic tacrolimus with extracorporeal photoporesis was begun with resolution of the pleural effusions and anasarca two months later. On d+903 he remains in CR3 and is on tapering courses of prednisone and tacrolimus without recurrence of the pleural effusions or anasarca. Conclusion: Isolated sterile pleural effusions with anasarca should be recognized as a rare feature of late onset chronic graft versus host disease so as to allow prompt initiation of immunosuppression. The patient shared the HLA antigens HLA DR15 and HLA DQW6 which are associated with autoimmune disease such as systemic lupus erythematosus suggesting that patients with this HLA combination may be more prone to this presentation. Disclosures:No relevant conflicts of interest to declare.

Random skin biopsy and bone marrow biopsy for diagnosis of intravascular large B cell lymphoma

Intravascular lymphoma (IVL) is a rare type of extranodal lymphoma in which the lymphoma cells proliferate exclusively in the lumina of small vessels. The diagnosis of IVL requires histological confirmation. Although random skin biopsy from healthy-appearing skin in patients with suspected IVL appeared to be useful, the sensitivity of this method for the diagnosis of IVL remains unknown. We performed a random skin biopsy from 12 consecutive cases of IVL diagnosed at our institution over the past 4years and evaluate its relevance of clinical and laboratory characteristics, presence or absence of skin lesions, and bone marrow involvement. All 12 patients were diagnosed antemortem by either random skin biopsy or bone marrow biopsy and treated with rituximab-containing chemotherapy. Random skin biopsy was performed in all 12 patients, and the results were positive in ten patients (83.3%). Erythematous skin lesions were seen in 3 of 12 patients, but biopsy was positive for lymphoma lesion in two patients. Bone marrow invasion was seen in 11 of the 12 patients (91.6%) by bone marrow smear and/or flow cytometric analysis, but was detected in only half of the patients by trephine biopsy. We concluded that random skin biopsy from normal-appearing skin is highly sensitive in the diagnosis of IVL comparable to bone marrow trephine biopsy. It should be performed irrespective of the presence or absence of skin lesions in patients who were suspicious of IVL.

Fluorodeoxyglucose-PET/CT for Diagnosis of Intravascular Large B-Cell Lymphoma

A 39-year-old woman was referred to our hospital with a 1-month history of recurrent fever. On physical examination, her spleen was palpable in the absence of peripheral lymphadenopathy and skin lesions. Laboratory studies yielded elevated values of serum lactate dehydrogenase at 1051 U/L, soluble interleukin 2 receptor at 24,500 pg/mL, and ferritin at 1019 μg/L. Blood cell counts showed a bicytopenia with a hemoglobin level of 7.0 g/dL and a platelet count of 3.7 × 109/L. Although the patient had no subjective symptoms such as dyspnea, her percutaneous oxygen saturation was low at 90%, suggesting hypoxemia. Findings on both chest radiography and computed tomography (CT) of the lungs were unremarkable. However, positron emission tomography (PET)/CT with 18F-fluorodeoxyglucose (FDG) revealed diffuse uptake in the bilateral lung, predominantly in the upper fields (Figure 1, A and B). In addition, FDG uptake was noted in the bilateral renal cortex (Figure 1, C) and vertebrae (Figure 1, A). Bone marrow aspiration yielded large atypical lymphoid cells with the appearance of hemophagocytosis. However, on bone marrow biopsy, lymphoma cells were not confirmed within the lumen of small blood vessels. Random skin biopsy specimens1 from normal-appearing skin on the patient's thigh revealed CD20+ large lymphoid cells filling the small vessels in the subcutaneous tissues (Figure 1, D and E). Intravascular large B-cell lymphoma (IVLBCL) was diagnosed. FIGURE 1. A-C, Positron emission tomography (PET)/computed tomography (CT) findings in a patient with intravascular large B-cell lymphoma. Characteristic pattern of 18F-fluorodeoxyglucose (FDG) uptake with diffuse accumulation in the bilateral lung field (A, B) ... Emerging evidence shows the usefulness of PET/CT in diagnosing lymphoma.2 However, its role in IVLBCL is unknown, mainly because of the rarity and the variety of its clinical presentation. Recently, we performed PET/CT in 4 consecutive patients who fulfilled the early diagnostic criteria for IVLBCL3 and found the characteristic pattern of FDG uptake: (1) diffuse accumulation in the bilateral lung field, (2) accumulation in the bilateral renal cortex, and (3) multiple accumulations in the bones (Figure 2, A-H). From an anatomic viewpoint, lungs and kidneys are affected by IVLBCL cells because these organs are rich in small blood vessels. Indeed, autopsies have revealed the high frequency of lymphomatous involvement in lungs and kidneys. We suggest that FDG-PET/CT be performed for early diagnosis of IVLBCL, which is important for effective therapeutic intervention. FIGURE 2. Positron emission tomography/computed tomography findings in patients with intravascular large B-cell lymphoma. A-C, Uptake of 18F-fluorodeoxyglucose (FDG) in the bilateral lung of a 74-year-old man, especially diffuse accumulation in the left lung field ...

Dermatitis cruris pustulosa et atrophicans revisited: our experience with 37 patients in south India

Dermatitis cruris pustulosa et atrophicans (DCPA) is a distinctive type of chronic superficial folliculitis, with a number of unique features such as its peculiar symmetric localization to legs, extreme chronicity, resistance to therapy, and inevitable alopecia and atrophy. All patients with DCPA, attending the Dermatology Outpatient Department at Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Hospital, Pondicherry, from December 2006 to June 2008 were included. Parameters recorded were detailed history and examination, hemogram, erythrocyte sedimentation rate, random blood sugar, skin biopsy and cultures from pus and carrier sites (nares, axillae and gluteal fold). 37 patients were studied (35 males and 2 females). Sixteen patients (43.24%) belonged to the 21-30 year-old age group. The disease most commonly began on the legs (81.1%). Majority (78.38%) had a disease duration of less than 5 years. Itching was the most common symptom (89.19%), followed by bleeding and scaling, with no significant systemic symptoms. The lower limbs were involved in all patients. Eleven patients (29.73%) had involvement of other sites--beard, axillae, chest, moustache, abdomen, and eyebrows. Pustules, papules, and scaling were seen in all patients, followed by wiry roughness, atrophy, alopecia, and pigmentation. Aggravating factors included use of full-length synthetic trousers, occupational exposure to potential irritants, and season (summer). Pus culture from the folliculitic lesions grew Staphylococcus aureus in 32 (86.49%) patients. Twenty one patients (56.75%) were carriers of S. aureus in one or more sites. DCPA is a chronic folliculitis of the legs, with a multifactorial etiopathogenesis, in which staphylococcal carrier status may be a new potential pathogenetic factor.

Asian Variant of Intravascular Large B-cell Lymphoma Diagnosed by Random Skin Biopsy

Asian Variant of Intravascular Large B-cell Lymphoma Diagnosed by Random Skin Biopsy

Evaluation of organ involvement in intravascular large B-cell lymphoma by 18F-fluorodeoxyglucose positron emission tomography

To evaluate the role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in intravascular large B-cell lymphoma (IVLBCL), we retrospectively analyzed four consecutive IVLBCL patients receiving FDG-PET before treatment between May 2006 and November 2007. Patients were two men and two women (median age 62 years, range 54-76 years). All patients received bone marrow biopsies and random skin biopsies and two of the four patients underwent renal biopsy for diagnosis. Accuracy of FDG-PET for the detection of organ involvements was analyzed by comparing results of pathological findings. Concordant results with respect to bone marrow involvement were accurately obtained for two patients. Skin and renal involvements were undetectable by FDG-PET regardless of positive pathological findings. One patient with a false-negative FDG-PET result showed fewer lymphoma cells in the bone marrow specimen than patients with concordant FDG-PET results. These results suggest false-negative results for some types of organ involvement. Careful interpretation of the results of FDG-PET in IVLBCL is thus required.

A clinicopathological study of 13 cases of intravascular lymphoma: experience in a single institution over a 9‐yr period

Intravascular lymphoma (IVL) is a rare type of extranodal lymphoma in which the lymphoma cells proliferate exclusively in lumina of small vessels. Here, we report a clinicopathological study of 13 cases IVL diagnosed at our institution between March 1999 and July 2007, and evaluated the clinical characteristics, usefulness of random skin biopsy and response to chemotherapy containing rituximab. Three of 13 patients were diagnosed at autopsy. The most common clinical features were unexplained fever, neurological deterioration, respiratory failure, and poor performance status. Thrombocytopenia, high serum lactate dehydrogenase and soluble interleukin2 receptor levels were the most common laboratory abnormalities. Adrenal tumor was detected in four cases and pituitary involvement was seen in all three autopsied cases and in two surviving patient by brain magnetic resonance imaging. Bone marrow invasion was seen in all 13 cases by bone marrow smear, and it was subtle in trephine biopsy. Immunohistochemical analyses revealed that CD5 was positive in one-third of the cases. Most of the cases were positive for MUM1/IRF, Bcl-2 and negative for CD10 and BCL-6 indicating the postgerminal center cell origin of this peculiar type of lymphoma. On random skin biopsy, the most recent seven patients were diagnosed promptly and chemotherapy containing rituximab was successfully administered. Patients with IVL exhibit the characteristic clinical and immunophenotypic features cited above and the use of random skin biopsy facilitates prompt diagnosis. Early commencement of chemotherapy containing rituximab appears promising for this peculiar lymphoma. As the recent seven patients were diagnosed by random skin biopsy over the past 13 months, the incidence of IVL is thought to be much higher than generally accepted.

Use of Random Skin Biopsy for Diagnosis of Intravascular Large B-Cell Lymphoma

Intravascular lymphoma (IVL) is a rare type of extranodal lymphoma with an aggressive clinical course characterized by proliferation of large lymphoma cells within the lumina of the small vessels. Because of its varied clinical symptoms and the absence of lymphadenopathy, diagnosis of IVL is extremely difficult and requires histological confirmation. We report here 6 consecutive patients with IVL, admitted to Kameda General Hospital, Kamogawa-shi, Japan, from June 7, 2006, to February 28, 2007, whose IVL was diagnosed by random skin biopsy of healthy-appearing skin. Three patients presented with progressive neurological deterioration and 2 others with hypoxemia with interstitial infiltration on chest radiography. One patient presented with confusion and severe hypoxia without apparent interstitial infiltration. Two patients showed localized skin involvement. Irrespective of the presence of skin lesions, almost all skin biopsy specimens showed obliteration of small vessels of subcutaneous fat tissues by lymphoma cells, allowing a prompt diagnosis of IVL. Early institution of rituximab-based chemotherapy induced favorable responses in all patients treated. Because diagnosis based on tissue other than skin is usually difficult in patients with suspected IVL, random skin biopsy should be considered even in patients with no evident skin lesions.

Use of Random Skin Biopsy for Diagnosis of Intravascular Large B-Cell Lymphoma

Use of Random Skin Biopsy for Diagnosis of Intravascular Large B-Cell Lymphoma

18F‐Fluorodeoxyglucose positron emission tomography for evaluation of intravascular large B‐cell lymphoma

A 73-year-old woman was referred to our hospital with a 1month history of recurrent fever, worsening mental state and general weakness. Physical examination showed confusion and mild splenomegaly but no peripheral lymphadenopathy or skin lesions. Her serum lactate dehydrogenase (LDH) and soluble interleukin-2 receptor were elevated to 1110 iu/l and 14 400 U/ml respectively. Computed tomography of the abdomen revealed mild hepatosplenomegaly and a right adrenal mass (top left panel). A bone marrow aspirate from the sternum showed scattered large atypical lymphoid cells (4AE2%) suggesting lymphoma infiltration. Based on our prior experience with intravascular lymphoma (IVL), we performed random skin biopsies from normal appearing skin on the trunk, thigh and upper arms. All specimens showed large lymphoid cells with irregular nuclei filling the small vessels in subcutaneous tissues (middle left panel). These cells were stained positively with CD20 (bottom left panel) and negatively with CD3 monoclonal antibody. A diagnosis of IVL of B-cell origin was made. F-Fluorodeoxyglucose positron emission tomography (F-FDG PET) was performed before treatment. In addition to intense uptake of the adrenal mass, increased F-FDG uptake was observed in the vertebrae, humeri, ulnae, radii and iliac crests (top right panels). After rituximab infusion (375 mg/m), her general condition and mental status improved rapidly. The serum LDH level was elevated transiently but returned to within normal limits over the next few days. After two courses of weekly rituximab and one course of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) chemotherapy, F-FDG PET (bottom right panels) scan was repeated, and no abnormal F-FDG uptake was observed. The patient entered complete remission and continued to receive additional treatment with rituximab and CHOP. IVL is a very rare subtype of non-Hodgkin lymphoma with an aggressive natural course. F-FDG PET scanning appears to be extremely useful for evaluating the early response to the chemotherapy in patients with IVL.

Intravascular B‐cell lymphoma diagnosed by skin biopsy

A 58-year-old man presented with unexplained fever, constitutional symptoms, worsening respiratory failure and gross, generalized oedema. He was eventually diagnosed with intravascular B- cell lymphoma on a random skin biopsy. Examination of the skin showed patchy erythema and induration, with peau d'orange. Despite multiorgan failure requiring intensive care, he responded dramatically to multiagent chemotherapy (six cycles of cyclophosphamide, doxorubicin, vincristine and prednisone) and is currently in clinical remission.

Use of random skin biopsy to diagnose intravascular lymphoma presenting as fever of unknown origin

Intravascular lymphoma is a rare extranodal non-Hodgkin’s lymphoma. Fewer than 150 cases have been reported in the English literature. Also known as malignant angioendotheliomatosis and angiotropic large cell lymphoma, it is a multisystem disease characterized by proliferation of malignant lymphoid cells within the lumen of small blood vessels. Its clinical presentation may include neurologic symptoms, skin lesions, and fever of unknown origin. The diagnosis of intravascular lymphoma requires histologic confirmation. Indeed, the majority of cases are diagnosed at autopsy ( 1 Demirer T. Dail D.H. Aboulafia D.M. Four varied cases of intravascular lymphomatosis and a literature review. Cancer. 1994; 73: 738-745 Crossref PubMed Scopus (207) Google Scholar ). We describe two patients who presented with fever of unknown origin and who did not have clinically evident skin involvement, in whom the diagnosis of intravascular lymphoma was established by random skin biopsies.

3713 SKIN BIOPSY IN APURPURIC AND PREPURPURIC HENOCHSCHONLEIN PURPURA.

Gastrointestinal (GI) manifestations can be severe in patients with HSP requiring steroids and sometimes plasmapheresis. 3-8% of children with HSP present without the characteristic rash but may have severe GI manifestations, making the diagnosis of HSP difficult. The radiologic and endoscopic findings are non specific. We describe 3 such patients, in whom the diagnosis of HSP was established by biopsy of the seemingly skin. In all cases the characteristic leukocytoclastic vasculitis with IgA deposits was found. The microscopic involvement of normal skin was not previously described in patients with HSP prior to the appearance of the rash. Patient 1: 7 year old girl presented with acute abdomen; laparotomy diagnosis was mesenteric adenitis. Progressive abdominal distension, ascites, and persistent fever lead to second laparotomy 10 days later. Congested small intestine with focal hemorrhages was found. Subsequent course was characterised by rectal bleeding, hypertension, nephritis and hematemesis. Endoscopy showed antral ulcer with hemorrhagis gastritis and duodenitis. Skin biopsy done one weeek later was diagnostic. Renal biopsy showed IgA nephropathy. Four weeks later, scanty purpuric rash appeared on the right arm and back. Patient 2: 6 year old boy presented with 10 day history of abdominal pains and bilious vomitings. Developed scrotal swelling and surgery showed epididymitis. Hematemesis, tender abdomen and high blood pressure were noted. Endoscopy showed hemorrhagic duodenitis and focal gastritis. Skin biopsy was diagnostic. He never developed purpuric rash. Patient 3: 6 year old boy presented with clinical appendicitis; laparotomy revealed congested terminal ileum. Post operative course was complicated by persistent abdominal pains, hematemesis, and rectal bleeding. Endoscopy showed hemorrhagic gastritis and colitis. Skin biopsy was diagnostic. He developed purpuric rash 2 days after biopsy. Other features of HSP included nephrotic syndrome, high blood pressure, and epididymo-orchitis. Renal biopsy showed IgA nephropathy. Random skin biopsy can be diagnostic in patients with HSP even when the characteristic rash is absent. This may lead to definitive diagnosis and treatment, precluding surgery and reducing morbidity in some cases. Increased use of skin biopsy and therefore increased recognition of atypical presentations of HSP may lead to redefinition of this syndrome.

Long-Term Efficacy and Safety of Jessnerʼs Solution and 35% Trichloroacetic Acid vs 5% Fluorouracil in the Treatment of Widespread facial Actinic Keratoses

Few studies have examined the long-term efficacy of fluorouracil (FU) or chemical peels for the treatment of actinic keratoses (AK). Our earlier work examined the efficacy and safety of a medium-depth chemical peel compared with the standard regimen of topical FU in the treatment of widespread facial AK through 12 months. To determine long-term efficacy of both treatments by extending our observations through 32 months. Fifteen patients with severe facial actinic damage were treated on the left side with a single application of Jessner's solution and 35% trichloroacetic acid and on the right side with twice daily applications of 5% FU cream for 3 weeks. Parameters evaluated at 1, 6, 12, and 32 months included counts of visible AK, random skin biopsies from both treatment areas, development of intercurrent neoplasms, and surveys assessing sun exposure. Eight patients were available for reevaluation at 32 months. Both treatment sides showed a reduction in mean number of AK at 12 months followed by an increase in mean AK number between 12 and 32 months. Improvements in biopsies of clinically actinically damaged skin were seen in keratinocytic atypia, hyperkeratosis, parakeratosis, and inflammation at all treatment times during the study with both treatments. Three squamous cell carcinomas developed in the patients after initial treatment; one developed on the side treated with the peel, and two developed on the side treated with fluorouracil. Surveys failed to demonstrate an association between sun exposure and clinical response. Based on these findings, patient with widespread actinic keratoses treated with medium-depth chemical peel or with 5% FU should be reevaluated yearly or every 1.5 years for reappearance of AK and retreatment.