Early clinical, histological, and immunohistochemical findings in suspected acute graft-versus-host disease and their association with patient outcomes.

BACKGROUND/OBJECTIVES: Acute graft-versus-host disease (aGVHD) is a serious condition after allogeneic hematopoietic stem cell transplantation (HSCT), frequently involving skin, gut, and liver. It can be difficult to diagnose early, yet this is vital for adequate management. We sought to identify initial clinical and histopathological features in children with suspected GVHD and the association with clinical course and outcomes. METHODS: Retrospective study of patients with skin biopsies for suspected aGVHD from 2006 to 2016. We collected demographic and clinical information, histologic, and immunohistochemical (IHC) findings, and outcomes during follow-up. Bivariate and multivariate analyses were done to identify risk factors associated with remission, development of severe/life-threatening aGVHD, and mortality. RESULTS: We included 42 patients, 15 females. Skin manifestations occurred 51 days (median) after HSCT. On biopsy, 76.2% had mild (stage 1-2) skin aGVHD; during the course of the disease, severity and systemic involvement increased to global grade III/IV in 66.6%. All patients received treatment; 15 are in remission from aGVHD and 23 have died. Histologic features were diagnostic in 83.3%. On bivariate and multivariate analysis, we identified initial clinical and histologic findings that were associated with the measured outcomes: odds of remission from aGVHD were increased when focal vacuolar changes were found on skin biopsy (OR 6.028; 95%CI:1.253-28.992) but decreased by initial hepatic aGVHD (OR 0.112; 95%CI: 0.017-0.748); severe/life-threatening aGVHD was associated with initial gastrointestinal aGVHD (OR 6.054; 95%CI:1.257-29.159); and odds of mortality were decreased with male donor (OR 0.056; 95%CI:0.004-0.804), nulliparous female donor (OR 0.076; 95%CI:0.009-0.669), and focal vacuolar changes on skin biopsy (OR 0.113; 95%CI:0.017-0.770). CONCLUSIONS: We found novel indicators predictive of remission, severity, and mortality in children with aGVHD. Further studies of this condition in children are needed.

Usefulness of the skin biopsy as a tool in the diagnosis of silvery hair syndrome.

BACKGROUND/OBJECTIVES: Silvery hair syndrome is a rare, autosomal-recessive entity characterized by silvery gray hair, eyebrows, and eyelashes and may be associated or not with immunologic or neurologic alterations. Two main types have been recognized: Chediak-Higashi syndrome and Griscelli syndrome. Hair shaft examination under light microscopy has been a useful tool to differentiate Chediak-Higashi syndrome from Griscelli syndrome, although distribution of melanin varies according to hair color related to ethnicity. The objective was to compare the pattern of melanin in the skin and with the pattern of melanin distribution in the hair shaft. METHODS: Sixteen patients with silvery hair syndrome were selected (Chediak-Higashi syndrome 5, Griscelli syndrome 11). The distribution of melanin granules in skin and hair shafts was compared and correlated with clinical diagnoses. RESULTS: Chediak-Higashi syndrome was characterized by small granules of melanin uniformly distributed throughout the thickness of the epidermis. Griscelli syndrome was characterized by an irregular pigment distribution in the epidermal basal layer with large and dense granules alternating with areas lacking melanin pigment. In two cases, study of the hair was not conclusive, but the skin showed the characteristic pattern of Griscelli syndrome. CONCLUSION: Skin biopsy is a useful tool in differentiating Chediak-Higashi syndrome from Griscelli syndrome and as a complementary study in cases in which hair shaft pigment distribution does not support the diagnosis, especially in patients with fair hair. The distribution of melanin granules in the skin correlates with that observed in the hair shaft, allowing Chediak-Higashi syndrome to be differentiated from Griscelli syndrome, at any age.

Hepatorenal Tyrosinemia in Mexico: A Call to Action.

Hepatorenal tyrosinemia is a treatable metabolic disease characterized by progressive liver failure, renal damage and pronounced coagulopathy. Its clinical diagnosis is difficult because of its low prevalence and heterogeneous symptoms. In developed countries, expanded newborn screening, based on succinylacetone quantification by tandem mass spectrometry, has been very valuable in the early detection of hepatorenal tyrosinemia, providing the opportunity for rapid treatment of affected patients. In developing countries without systematic expanded newborn screening, however, diagnosis and treatment of this disease remain major challenges, as genetic diseases in these countries are not a health priority and there are few referral centers for infants with inherited errors of metabolism. This chapter describes the diagnosis, follow-up and outcome of 20 Mexican patients with hepatorenal tyrosinemia. This chapter also constitutes a call to action to pediatricians, gastroenterologists, geneticists and other health professionals, and to academic organizations, health authorities and patient advocacy groups, to promote early patient detection and treatment, reducing the unacceptably high mortality rate (75%) in Mexican infants with this potentially deadly but eminently treatable condition.

Intestinal/Peritoneal tuberculosis in children: an analysis of autopsy cases.

Infection by Mycobacterium bovis is not infrequently identified in Mexico. Its relation to nonpasteurized milk products ingestion is well recognized with primary infection usually in the intestinal tract. The term "abdominal tuberculosis" includes peritoneal as well as primary and secondary intestinal tuberculosis. The clinical differentiation of these conditions is difficult. In this work, we reviewed the clinical and pathological features of 24 cases of children dying with tuberculosis in whom autopsy revealed abdominal disease in a referral hospital in Mexico City. We identified 8 cases of primary intestinal tuberculosis, with documentation of M. bovis in 6 of them, and 9 cases of secondary intestinal tuberculosis (primary pulmonary disease), all negative to M. bovis. Seven patients had peritoneal tuberculosis without intestinal lesions and with active pulmonary disease in 4 of them, and of the remaining three, two had mesenteric lymph node involvement suggesting healed intestinal disease. In this approach to abdominal tuberculosis, postmortem analysis was able to differentiate primary from secondary intestinal tuberculosis and to define the nature of peritoneal involvement. This discrimination gives rise to different diagnostic approaches and epidemiological and preventive actions, particularly in countries where tuberculosis is endemic and infection by M. bovis continues to be identified.

Portopulmonary hypertension in children. A study in pediatric autopsies.

BACKGROUND AND AIMS: The relative frequency and risk factors of portopulmonary hypertension in children have not been defined with precision. The few published reports refer to isolated cases or small series from selected populations. The development of pulmonary hypertension in patients with portal hypertension is seldom suspected or documented during life. The examination of autopsy material can identify these cases because pulmonary hypertension produces characteristic histological changes in the pulmonary vasculature. METHODS: Autopsy cases with evidence of portal hypertension were retrieved. Slides of pulmonary tissue from these cases were examined in search of histopathological changes of hypertensive arteriopathy RESULTS: Seventy six cases of portal hypertension were identified among 7060 autopsies collected between January 1971 and January 2008 (1.07%). Four cases with histopathological evidence of pulmonary hypertension were identified. This represents 5.2% of all cases with portal hypertension. These four patients were females in late childhood or adolescence with idiopathic portal hypertension. Pulmonary hypertension was not diagnosed during their lifetime. CONCLUSIONS: Idiopathic portal hypertension in adolescent girls should be considered a risk factor for the development of portopulmonary hypertension, very likely as a consequence of the functional preservation of hepatic tissue that allows a prolonged survival. An oriented search for early signs of pulmonary hypertension in these patients would appear advisable in order to install timely treatment.

Exogenous lipoid pneumonia superinfected with acid-fast bacilli in infants: a report of nine cases.

Super-infection of an exogenous lipoid pneumonia by nontuberculous mycobacteria has been described in the literature. It produces a distinctive histologic picture with suppurative, noncaseating granulomas surrounding lipid vacuoles containing acid-fast bacilli. Mainly isolated cases have been found, but seldom in children. We describe a series of 9 children with similar histological findings. All our patients were under 1 year of age, malnourished, and with chronic respiratory symptoms. The diagnosis, based on the characteristic histology with acid-fast rods, was established at autopsy in 4 cases, on lobectomy specimens in 4 and by open lung biopsy in 1. Mycobacterium fortuitum-chelonei was cultured in 1 case. Gastro-esophageal reflux was documented in all 4 cases in which it was explored. Aspiration of lipid gastric contents or of oil given as medication can result in exogenous lipoid pneumonia, which in turn becomes super-infected with mycobacteria. Recognition of the distinctive histology permits the diagnosis of this complication.

Video-assisted thoracoscopy for diaphragmatic plication: experimental study in a canine model.

BACKGROUND: Plication of a nonfunctional hemidiaphragm usually restores altered ventilatory mechanics. This study compared two techniques in performing diaphragmatic plication: video-assisted thoracoscopy (group A) and thoracotomy (group B). MATERIALS AND METHODS: Twenty dogs with induced paralysis of the right hemidiaphragm were randomly assigned to one of the two groups. Evaluations were performed before and after plication of the respiratory frequency (f) and lung area (LA) of the affected side. Operative time, time to resumption of walking, ingestion of fluids and solid food, pain intensity, and postoperative complications were measured. RESULTS: Group A had less pain after the surgery (P < 0.0001), earlier fluid ingestion (P < 0.05), and earlier resumption of walking (P < 0.019). Four weeks after the procedure, LA was similar in both groups, while a significant decrease in f was recorded in group A (P < 0.02). The remaining evaluated variables showed no differences. CONCLUSION: Both approaches were effective. Pain recorded in the postoperative period was less and recovery was faster in group A. Complications and surgical times were similar. The video-assisted thoracoscopy is a safe and efficient option for performing diaphragmatic plication in dogs.

[Clinicopathologic cases]. / Los casos clínicopatológicos.

The clinicopathologic conference (CPC) was introduced by Dr. Richard C. Cabot at the Massachusetts General Hospital in the U.S. early in the past century. In a short time, it became one of the most popular medical teaching tools in the world. Despite certain differences between beside diagnosis and CPC diagnosis, the latter is a valuable teaching exercise. During the past few decades, interest in CPCs has declined due to several issues: excessive concern with anatomic diagnosis at the expense of molecular pathogenesis and pathophysiology; emphasis on uncommon diseases; the pathologist being considered an adversary who enjoys demonstrating clinical discussion errors; autopsies failing to reveal abnormalities in physiopathologic disorders and it is not rare to fail to reveal cause of death, and the fact that very few cases are true diagnostic problems, due to advances in diagnostic techniques. In addition, with the decline of interest in autopsies during the past years, in several CPCs, many final diagnosis is performed by biopsy, laboratory tests, or imaging studies. The ideal CPC case to conserve the educational role of this exercise is an autopsy case with adequated clinical, laboratory and/or imaging studies.

Las sesiones anatomoclinicas en Mexico en los albores del siglo XXI / Postmortem clinical anatomy sessions in Mexico at the dawn of the 21st. century

The authors present a defense of postmortem clinical anatomy sessions, which contributed enormously to the development of clinical medicine but which today draw little interest in medical studies. Nevertheless, the sessions still provide an unrivalled exercise in diagnosis for medical students and an excellent method of continuing education for practicing professionals. Autopsies make it possible to confirm or correct clinical diagnoses, including those obtained through highly complex technological procedures; they contribute to the discovery of new diseases and other abnormalities; they promote research; they provide reliable statistics on morbidity and mortality; they produce useful genetic information; they facilitate interdisciplinary discussion and knowledge exchange; and they can serve as an indicator of the quality of medical care. The authors recommend reviving the high academic standards of postmortem clinical anatomy sessions and urge professionals in health institutions to contribute as much as possible to the continuation and improvement of these sessions

Opportunistic infections in children with AIDS/HIV. A study of twenty five autopsies from the National Institute of Pediatrics in Mexico City

Veinticinco niños que murieron con SIDA/infección por VIH fueron sometidos a estudio postmortem; representan el 1.5 por ciento de las autopsias efectuadas desde enero de 1986 a junio de 1996. incluyen 16 pacientes infectados por vía materna y 6 por transfusión. Solo un caso se infectó por vía sexual y en dos casos se desconoce el mecanismo de infección. La infección materna en los 16 casos de infección vertical fue por transfusión prenatal en 5 transfusión postnatal en 4, sexual en 5 y no se determinó en un caso. La infección secundaria fue la causa de muerte en 23 de los 25 casos. La infección bacteriana estuvo presente en 56 por ciento de los niños infectados por vía materna y en 33 por ciento de los infectados por transfusión. Pseudomonas en 6 casos y Salmonella B en 4 fueron las bacterias mas frecuentes. Los gérmenes oportunistas fueron frecuentes, en especial Histoplasma (4 casos), Citomegalovirus (9 casos) y Herpes/Varicela (5 casos)

Papilomatosis respiratoria recurrente y carcinoma broncogénico multicéntrico asociado a HPV 11/6. Presentación de un caso y revisión de la literatura / Recurrent respiratory papillomatosis and multicentric bronchogenic carcinoma associated with HPV 11/6. Report of a case and review of the literature

Un niño de 12 años de edad, con papilomatosis respiratoria recurrente desde los 8 meses de edad, fue sometido a más de setenta resecciones y falleció con una lesión pulmonar destructiva basal derecha. En la autopsia se encontró extensa papilomatosis que afectaba laringe, traquea y bronquios principales y se extendía a bronquiolos terminales y alveolos. El parenquima pulmonar tenía focos de carcinoma epidermoide, ocasionalmente mezclado con celulas malignas mucoproductoras, y se encontró una metástasis en un ganglio hiliar derecho. Las sondas biotiniladas para ADN del virus del papiloma humano 11/6 hibridizaron tanto con las lesiones papilomatosas como con las áreas de carcinoma. Los pacientes con papilomatosis respiratoria que desarrollan carcinoma broncogénico a partir de papilomatosis bronquiolo alveolar son mas jovenes y tiene un curso clínico mas agresivo, con diseminación metástasica, mientras que en los pacientes, no fumadores y no radiados, que desarrollan carcinoma laringotraqueal, el tumor muestra solo agresividad local