The grim reaper evading modern medicine: aspergillosis, adenovirus, and Hodgkin lymphoma

Illustrative cases of diseases that are difficult to suspect and diagnose can serve as useful reminders. Invasive pulmonary aspergillosis and adenovirus hepatitis are two such diseases, both revealed by autopsy in this case of Hodgkin lymphoma refractory to chemotherapy treated with allogeneic hematopoietic stem cell transplantation complicated by these two fatal infections. This patient was cured of Hodgkin lymphoma, Clostridioides difficile colitis and thrombotic thrombocytopenic purpura using the marvels of modern medicine. This case illustrates many features of aspergillosis and adenovirus hepatitis, shows the value of autopsy in revealing diagnoses, and illustrates the limits of modern medicine, which should serve as a mental spur in our efforts to advance medical science, to try to defeat the numerous demons of disease, who seem to keep outwitting us.

Necrolisis epidérmica tóxica en el curso de un síndrome hemofagocítico secundario a linfoma de Hodgkin: caso clínico / Toxic epidermal necrolysis during a hemophagocytic syndrome secondary to Hodgkin lymphoma: report of one case

Toxic epidermal necrolysis (TEN) is a lethal entity, characterized by extensive epidermal necrosis and multiorgan failure. Hemophagocytic syndrome (HFS) is also a rare and lethal syndrome characterized by hyperinflammation that leads to the appearance of fever, pancytopenia, organomegaly and hemophagocytosis. The concomitance of these diseases is extremely uncommon. We report a 38 years old female, who during the course of a HFS secondary to Hodgkin Lymphoma (HL), presented a TEN secondary to antibiotics. She was admitted due to a consumptive syndrome, lymphadenopathy, visceromegaly and severe pancytopenia. Laboratory and bone marrow tests confirmed HFS. Due to constant fever, imipenem was indicated. On the third day she started with pain and skin rash. She evolved with positive Nikolsky sign. Cutaneous biopsy was concordant with extensive TEN, which was managed with intravenous immunoglobulin and dexamethasone. A complete response and normalization of the blood count were achieved. Finally, the lymph node biopsy showed HL of mixed cellularity type, which was managed with 8 cycles of ABVD chemotherapy, achieving complete remission.

Linfoma de Hodgkin y no Hodgkin durante la gestación: a propósito de dos casos / Hodgkin's and non-Hodgkin during pregnancy: report of two cases

Las neoplasias hematológicas en el embarazo conllevan un gran riesgo para la madre y el feto. El linfoma, Hodgkin (LH) y no Hodgkin (LNH), es la cuarta causa más frecuente de cáncer diagnosticado en el embarazo. El tipo más frecuente es el LH, mientras que la incidencia de LNH es muy baja. Presentamos dos casos de gestantes de 29 y 25 años, diagnosticadas en el segundo trimestre de la gestación de LNH mediastínico de células B y LH tipo esclerosis nodular respectivamente. Ambas fueron tratadas con quimioterapia desde el diagnóstico hasta dos semanas antes del parto, con buen resultado perinatal.

Haematological cancer in pregnancy poses a substantial risk to both, mother and fetus. Lymphoma, including Hodgkin's lymphoma (HL) and Non-Hodgkin's lymphoma (NHL), is the fourth most frequent malignancy diagnosed during pregnancy. The most common type of lymphoma in this setting is HL, and the incidence of pregnancy associated NHL is very low. In this report we describe two cases of a 29-year-old woman and a 25-year-old woman both in the second trimester of pregnancy, diagnosed with mediastinal B-cell NHL and nodular-sclerosis HL respectively. They were managed with chemotherapy since the diagnosis as far as two weeks before the delivery, both with a successful fetal outcome.

Ictericia febril colestásica como forma de presentación de linfoma de Hodgkin / Febrile cholestatic jaundice as an initial manifestation of Hodgkin's disease

La ictericia febril colestásica como forma de presentación de los linfomas de Hodgkin es un cuadro muy infrecuente. Describimos aquí un caso de síndrome febril prolongado asociado a ictericia progresiva, en el que el diagnóstico de la enfermedad se realiza a través de la biopsia hepática, dada la ausencia de afectación ganglionar que caracteriza a esta enfermedad. Destacamos asimismo el cuadro clínico avanzado y el compromiso multisistémico de una enfermedad rápidamente evolutiva.

The febrile cholestatic disease as a presentation of Hodgkin's lymphoma is a very unusual condition. We describe here the case of a patient with prolonged fever of unknown origin and progressive jaundice, in whom the diagnosis was made with the analysis of a liver biopsy, given the absence of lymph node involvement that characterizes this disease. We remark the severe and multisystemic involvement of this rapidly progressive disease.

Causas de mortalidad en pacientes con linfoma de Hodgkin / Causes of mortality in patients with Hodgkin lymphoma

Se realizó un estudio retrospectivo-descriptivo en el Servicio de Hematología del Hospital Clinicoquirúrgico Hermanos Ameijeiras para conocer las causas de muerte en pacientes con diagnóstico de linfoma de Hodgkin tratados desde enero de 1983 hasta diciembre de 2008. De los 619 pacientes diagnosticados en ese período, la muestra quedó constituida por 443, de los cuales 287 (64,8 por ciento)se encontraban vivos al final del estudio y 156 (35,2 por ciento)habían fallecido. La recaída/progresión de la enfermedad fue la causa más importante de muerte, independientemente de la edad de presentación, la modalidad de tratamiento empleada y el tiempo de evolución (125 pacientes, 80 por ciento). El 20 por ciento restante de las muertes ocurrió por segundas neoplasias en 10 pacientes (6,4 por ciento )complicaciones del tratamiento en 8 (5,1 por ciento ), complicaciones infecciosas fatales en 2 (1,2 por ciento) y enfermedad cardiovascular en 3 (1,9 por ciento). En 8 pacientes (5,1 por ciento) no se precisó la causa de muerte. Las segundas neoplasias predominaron en pacientes de 40-59 años, que recibieron la modalidad de tratamiento combinada y con menos de 10 años de evolución

A retrospective descriptive study was conducted in the Hematology Service at Hermanos Ameijeriras Hospital to know the causes of death in patients with Hodgkin lymphoma, who were treated from January 1983 to December 2008. Out of 619 patients diagnosed in that period, the total sample was formed by 443 patients. 287 (64.8 percent) of them were alive at the end of the study, and 156 (35.2 percent) had died. This disease relapse/progression were the leading cause of death, regardless age of its presentation, treatment used, and the time of progression (125 patients, 80 percent). The remaining 20 percent of deaths occurred from secondary malignancies in 10 patients (6.4 percent), complications of treatment in 8 (5.1 percent), fatal infectious complications in 2 (1.2 percent), and cardiovascular disease in 3 (1.9 percent). In 8 patients (5.1 percent) the cause of death was not stated. Secondary malignancies were predominant in patients aged 40-59, who received combined treatment with less than 10 years of evolution

Prevalence and aetiology of anaemia in lymphoid malignancies.

Background. We prospectively studied the prevalence, type and causes of anaemia in newly diagnosed patients with lymphoid malignancies. Methods. Between January 2007 and June 2008, a total of 316 newly diagnosed, consecutive patients (aged 15 years or above) of Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia with anaemia (haemoglobin <11 g/dl), were analysed to determine the prevalence and a subgroup of 46 patients was analysed for the cause of anaemia. Results. Hodgkin lymphoma, non-Hodgkin lymphoma and chronic lymphocytic leukaemia were the diagnoses in 81 (25.8%), 203 (64.7%) and 30 (9.6%) patients, respectively. Anaemia was present in 134 patients (42.4%). Anaemia of chronic disease was present in 33/46 (71.7%) and iron deficiency in 18/46 (39.1%) patients. Vitamin B12 and/or folate deficiency was detected in 10/46 (21.7%) patients (B12 deficiency alone in 7, folate deficiency alone in 1 and combined B12 and folate deficiency in 2). Autoimmune haemolytic anaemia was detected in 5/46 (10.9%) although direct Coombs test was positive in 17/46 (37%) patients. Among patients with Hodgkin lymphoma and non-Hodgkin lymphoma, anaemia due to bone marrow involvement was present in 16/40 (40%). In most patients with bone marrow involvement, anaemia was due to other causes. In only 3 patients, anaemia was attributable to bone marrow involvement alone. Anaemia was multifactorial in 18/46 (39.1%) patients. Nutritional deficiency alone or in combination was present in 22/46 (47.8%) patients. Conclusion. Anaemia is common in lymphoid malignancies at initial presentation. Besides managing anaemia of chronic disease and bone marrow involvement, nutritional and autoimmune causes should be ruled out.

Síndrome de vena cava superior: forma inicial de presentacion en enfermedades neoplásicas / [Superior Cava Venous syndrome as presentation of neoplasic disease].

Superior Cava Venous Syndrome (SVCS) encompasses a constellation of signs and symptoms resulting from partial or complete obstruction of blood flow through the superior vena cava (SVC) to the right atrium. Thrombosis can be caused by intrinsic (primary) or extrinsic compression (with or without secondary thrombosis). The causes of SVCS can be grouped according to their etiology in non-neoplastic and neoplastic. The causes malignant correspond to 65-90

of them, thrombosis and nonmalignant conditions are another causes. The presentation may be acute, clinically characterized by dyspnea and a characteristic triad (facial, neck and arms edema, cyanosis and collateral circulation). Early detection improves prognosis and is based on clinical data and imaging studies. We describe 8 cases where the SVCS was the first manifestation of neoplastic diseases. Patients were predominantly of middle-aged, male, without association with consumption of tobacco and lymphoma was most frequent diagnosis.

Vanishing bile duct syndrome in a Hodgkin's lymphoma patient with fatal outcome despite lymphoma remission

Vanishing bile duct syndrome [VBDS] is a condition resulting from severe bile duct injury, progressive destruction, and disappearance of intrahepatic bile ducts [ductopenia] leading to cholestasis, biliary cirrhosis, and liver failure. VBDS can be associated with a variety of disorders, including Hodgkin's lymphoma [HL]. We describe a 33-year-old male patient who presented with lymphadenopathy and jaundice, and was diagnosed to have HL. Serum bilirubin worsened progressively despite chemotherapy, with a cholestatic pattern of liver enzymes. Diagnosis of VBDS was established on liver biopsy. Although remission from HL was achieved, the patient died of liver failure. Presence of jaundice in HL patients should raise the possibility of VBDS. This report discusses the difficulties of delivering chemotherapy in patients with liver dysfunction. HL-associated VBDS carries a high mortality but lymphoma remission can be achieved in some patients. Therefore, liver transplantation should be considered early in these patients.

Prolonged jaundice attributed to super infection of hepatitis E virus in a case of resolving leptospirosis.

India is endemic for both Leptospira and hepatitis E virus (HEV). The clinical presentations of these diseases have overlapping features. We report a case of superinfection of HEV in a patient with resolving leptospirosis with underlying Hodgkin lymphoma. The diagnosis of HEV in our case was established by HEV-RNA PCR as our patient was immunosuppressed. The present study highlights the need for molecular diagnosis in the case of HEV infection with strong clinical suspicion and negative serological results.

Spectrum of malignancies among HIV-infected patients in South India.

Introduction: The current study examines the spectrum of malignancies among HIV-infected South Indians enrolled in a clinical care program. Materials and Methods: We conducted a nested matched case-control study among 42 HIV-infected cases who developed cancer and 82 HIV-infected controls between 1998 and 2008 at a tertiary care HIV care program in South India. Results: The most common types of cancer included non-Hodgkin's lymphoma (38.1%), Hodgkin's lymphoma (16.7%), squamous cell carcinoma (14.3%), and adenocarcinoma (14.3%). The median duration of time from HIV infection to cancer diagnosis was 549 days [interquartile range (IQR): 58-2013]. The nadir CD4 cell count was significantly lower in cases compared to controls (134 cells/μl vs. 169 cells/μl; P = 0.015). Cancer patients were more likely to have a more advanced HIV disease stage at the time of cancer diagnosis compared to control patients (Stage C: 90.5% vs. 49.4%; P<0.0001). Significantly more cancer patients were receiving antiretroviral treatment relative to control patients at the time of cancer diagnosis (92.9% vs. 66.3%; P=0.001). Conclusions: HIV-infected patients who developed cancer had more advanced immunodeficiency at the time of cancer diagnosis and a lower nadir CD4 cell count. It is possible that with the continued roll-out of highly active antiretroviral therapy in India, the incidence of HIV-associated malignancies will decrease.

Langerhans Cell Histiocytosis Followed by Hodgkin's Lymphoma

A 22-year-old man was referred to our institution due to lower back pain and was diagnosed with Langerhans cell histiocytosis of the thoracic and lumbar spine. The patient achieved complete remission with radiotherapy and chemotherapy. One year later, right cervical lymphadenopathy was observed and Hodgkin's lymphoma was confirmed on biopsy. The patient was treated with chemotherapy and autologous stem cell transplantation, and experienced no further symptoms. Further, no evidence of recurrence was observed on follow-up imaging. This report discusses the association between Langerhans cell histiocytosis and Hodgkin's lymphoma.

Síndrome de Sweet associada a linfoma de Hodgkin: relato de caso / Sweet's Syndrome associated with Hodgkin's disease: case report

A síndrome de Sweet é enfermidade cutânea rara e de etiologia pouco esclarecida. Cerca de 20 por cento dos casos são associados a neoplasias hematológicas, sendo raros os casos relacionados à doença de Hodgkin. Relata-se caso de paciente masculino de 57 anos que desenvolveu a síndrome concomitantemente à neoplasia. As doenças foram controladas com o tratamento específico.

Sweet's syndrome is a rare cutaneous disease of unknown etiology. About 20 percent of the cases are associated with hematological neoplasms, and cases related with Hodgkin's disease are rare. We present the case of a 57-year old male patient who developed the syndrome concomitantly with the neoplasm. The diseases were controlled with specific treatment.

Un caso de melioidosis en la Argentina / A case of melioidosis in Argentina

Se describe el caso de un varón de 17 años oriundo de República Dominicana, con antecedente de linfoma de Hodgkin, que presenta tumoraciones blandas con supuración espontánea. En sus cultivos desarrolló Burkholderia pseudomallei, agente etiológico de la melioidosis. El paciente recibió tratamiento antibiótico con imipenem y luego con amoxicilina-ácido clavulánico con muy buena evolución clínica del proceso infeccioso. En razón de la baja incidencia de Burkholderia pseudomallei en nuestro continente el diagnóstico de melioidosis pudo haber sido subestimado. Su diagnóstico definitivo depende del aislamiento e identificación del agente causal en la muestra clínica.

We describe a case of 17-year- old man native of Dominican Republic, with Hodgkin´s lymphoma, who presented soft espontaneous draining nodules. In the clinical samples grew Burkholderia pseudomallei; the etiological agent of melioidosis. He received antimicrobial treatment with imipenem and amoxicillin/clavulanic with very good clinical evolution of the infectious process. Melioidosis diagnosis could be underestimated due to the low incidence of Burkholderia pseudomallei in our continent. The definitive diagnosis depends of the isolation and identification in the clinical sample.

A 12-year-old girl with hodgkin’s disease presenting as a non-resolving pneumonia and an endobronchial nodule.

The presence of a non-resolving pneumonia warrants the suspicion of a possible malignancy. While pulmonary involvement in Hodgkin’s disease can present as a non-resolving pneumonia, the clinical clues of dyspnoea, stridor and wheeze point to a possible endobronchial involvement. A bronchoscopy in such a situation can be valuable for diagnosis, and can aid in staging of the disease. The true incidence of endobronchial involvement in Hodgkin’s disease is not known, but when diagnosed early and treated appropriately, the prognosis is usually good, and a complete cure is possible.

Associação de ictiose adquirida, linfoma de Hodgkin e Hepatite B / Combination of acquired ichthyosis, Hodgkin’s lymphoma and Hepatitis B

Ictiose adquirida é um distúrbio raro da queratinização, associado a diversas doenças, como neoplasias. Aqui relatamos o caso de uma paciente que se apresentou com ictiose de início recente e no decorrer da investigação foi descoberta hepatite B crônica e linfoma de Hodgkin. Não encontramos relatos da associação destas três entidades na literatura.

Acquired Ichthyosis is a rare disorder of keratinization associated with several diseases such as neoplasias. Here we report the case a patient presenting with ichthyosis of recent onset, and along the investigation chronic hepatitis B and Hodgkin lymphoma were diagnosed. No previous report of the combination of these three entities was found in the literature.

Secuelas Endocrinológicas del Tratamiento de las Enfermedades Oncológicas en la Infancia y Adolescencia / Endocrinological schools of the Treatment of Oncological Diseases in Childhood and Adolescence

Los avances en el tratamiento de las enfermedades oncológicas en la infancia y adolescencia han permitido que la tasa de sobrevida en niños tratados por cáncer aumente progresivamente. Alrededor del 70% de los pacientes pediátricos tratados por tumores del SNC, el 80% por leucemias linfoblásticas agudas y más del 90% por linfoma de Hodgkin sobreviven a los mismos. Los trastornos endocrinos de los diferentes ejes se observan en un alto porcentaje de los sobrevivientes, debido a afecciones producidas por la enfermedad de base, el tratamiento o intercurrencias. Muchas de estas anomalías pueden sobrevenir años o décadas luego del tratamiento. La terapéutica de estas enfermedades comprende diferentes esquemas incluyendo cirugía, quimioterapia y radioterapia. Estos intensos esquemas de tratamiento pueden tener como consecuencia la aparición de diversas secuelas; 40% de los pacientes tratados por enfermedades oncológicas en la infancia va a tener alguna secuela endocrina relacionada con la enfermedad de base, la cirugía, la radio y/o quimioterapia; dependiente de la edad al inicio de la enfermedad y/o tratamiento, el género y el tiempo transcurrido desde la finalización del tratamiento. Postradioterapia craneal el orden de alteración de los ejes es 1) eje somatotrófico, 2) eje gonadotrófico, 3) eje adrenocorticotrófico y 4) eje tiroideo. La radio y quimioterapia pueden producir daño gonadal primario siendo el epitelio germinal del varón el más susceptible. La recuperación a medida que se aleja de la finalización del tratamiento es infrecuente, pero posible. Es de suma importancia conocer las posibles alteraciones con el objeto de realizar un adecuado control de los pacientes, durante su infancia y adolescencia y en la vida adulta. Con este fin se recomienda: • Una observación semestral del crecimiento y desarrollo puberal, en todos los niños tratados por neoplasia maligna, hasta que alcancen su estatura adulta y completen su desarrollo sexual. Se deberá prestar especial atención al inicio precoz de los signos puberales y a la falta de aparición de los mismos dentro del rango de edad esperado. • Un control anual de la función tiroidea, que incluya los valores de TSH y hormonas tiroideas, examen clínico con palpación de la glándula y ecografía. • El nivel de cortisol matinal debe ser determinado anualmente por un período de hasta 15 años luego de la finalización del tratamiento oncológico.

Most children diagnosed with a malignancy may now be expected to become long term survivors. The overall survival rate for childhood cancers is greater than 70% for pediatric central nervous system tumors, 80% for acute lymphoblastic leukemia and exceeds 90% for those diagnosed with Hodgkin´s disease. Endocrine sequelae, ranging from 20 to 50%, have been documented in these children, related to the underlying condition, the nature and dosage of cytotoxic chemotherapy and the amount and schedule of irradiation. Long term effects affecting the endocrine system represent a frequent complication of treatment and many of these endocrine disturbances could develop several years after the completion of treatment schedules. Several factors as age at which treatment was initiated, the length of time since treatment and gender modified these long term late effects. There is a strong association between the total radiation doses and pituitary hormone deficiencies. The growth hormone axis is the most sensitive followed by the gonadotropic and thyrotropic axes. Radio and chemotherapy cause male and female gonadal dysfunction Patients at risk of developing endocrinologic sequelae must be identified and monitored closely to assess the magnitude of any late effects in order to prevent associated morbidity. The following are the recommendations of the Children´s Oncology Group for the surveillance of these group of patients: • Semi-annual screening of growth in all children. Pubertal onset and tempo should be assessed to detect precocious, early, late puberty or gonadal failure. • Annual screening including clinical examination and levels of T4 and TSH. • Serum cortisol levels should be obtained yearly until 15 years off therapy.

Frequency of bone marrow involvement in Hodgkin's lymphoma on first presentation

To determine the frequency of bone marrow involvement in patients of Hodgkin's lymphoma on first presentation at oncology department. Case series. The Oncology Department, Combined Military Hospital, Rawalpindi, from April 2006 to February 2007. Thirty five patients of Hodgkin's lymphoma diagnosed on lymph node biopsy presenting for the first time at Oncology Department, Combined Military Hospital, Rawalpindi were included. They were admitted in the ward and evaluated with history, physical examination and staging investigations. Bone marrow trephine biopsy was performed in all patients. Descriptive statistics were used to analyze data. On clinical and radiological evaluation, 8 patients [22.9%] had clinical stage [CS], 12 [34.3%] had CS II, 9 [25.7%] had CS III and 6 [17.1%] had CS IV. The microscopic appearance in bone marrow trephine examination showed lymphoma infiltrates in 6 [17.14%] patients and chronic disorder in 29 [82.85%] patients. Among patients with bone marrow infiltration, one had CS II disease, three had CS III disease and two had CS IV disease. One patient had bone marrow infiltration as the only manifestation of disease. Bone marrow involvement was seen in patients with Hodgkin's lymphoma clinical stage II or higher

Cytomegalovirus Induced Gastric Ulcer as a Principal Manifestation in the Initial Stage of Hodgkin's Disease / 대한소화기학회지

Cytomegalovirus (CMV) is an important cause of opportunistic infection in immunocompromised patients. CMV infection occurs as a result of the cell-mediated immunity change in lymphoma patients. Although CMV can cause ulceration anywhere in the gastrointestinal (GI) tract in immunocompromised patients, only a few case reports about CMV GI infection in malignant lymphoma have been documented in literature. Furthermore, it was rare that CMV gastric ulcer with massive bleeding presented as an initial manifestation in a patient who has been not diagnosed lymphoma. We report a case of CMV induced gastric ulcer as an initial manifestation in patient with Hodgkin's disease.

Primary lymphoma of the breast: a clinicopathological study.

3 cases of primary non Hodgkins lymphoma of the breast are described, seen over a period of 2 years among 199 cases of breast malignancies. All were diffuse large B cell type. Application of immunohistochemistry greatly aids in differentiating lymphoma from anaplastic carcinoma, with which it can easily be confused. Preoperative diagnosis on a trucut biopsy is an ideal diagnostic method since diagnosis on fine needle aspiration cytology or frozen section may not be possible. Primary breast lymphoma is a rare disease with reported incidence of 0.04-0.53% of all breast malignancies in most series. Accurate diagnosis is essential, so that appropriate treatment may be applied. Two cases were treated with CHOP chemotherapy and radiotherapy along with surgical excision. One case was treated with CHOP chemotherapy.