Pulmonary Langerhans cell histiocytosis: the many faces of presentation at initial CT scan.

OBJECTIVES: Pulmonary Langerhans cell histiocytosis (PLCH) is a rare interstitial granulomatous disease that usually affects young adults who are smokers. Chest computed tomography (CT) allows a confident diagnosis of PLCH only in typical presentation, when nodules, cavitated nodules and cysts coexist and predominate in the upper and middle lungs. METHODS: This article includes a pictorial essay of typical and atypical presentations of PLCH at initial chest CT. Various appearances of PLCH are illustrated and possible differential diagnosis is discussed. RESULTS: PLCH can present with some aspecific features that may cause diagnosis of the initial disease to be overlooked or other pulmonary diseases to be suspected. In cases of nodule presentation alone, the main differential diagnosis should include lung metastasis, tuberculosis and other infections, sarcoidosis, silicosis and Wegener's disease. In cases of cysts alone, the most common diseases to be differentiated are centrilobular emphysema and lymphangiomyomatosis. Clinical symptoms are usually non-specific, although a history of cigarette smoking, coupled with the presence of typical or suggestive findings at imaging, is key to suspecting the disease. Atypical presentations require surgical biopsy for diagnosis. CONCLUSIONS: The radiologist should be familiar with PLCH imaging features to correctly diagnose the disease or need for further investigation. TEACHING POINTS: • PLCH is a rare interstitial smoking-related disease that usually affects young adults. • The typical first CT shows a mix of nodules, cavitary nodules and cysts in the upper-middle lungs. • Atypical appearance, either cysts or nodules alone, mandates that other diagnoses be considered. • Lung cystic involvement correlates with lung function abnormalities and predicts functional decline. • Integration of the clinical history and imaging results is key to diagnosis.

Immunosuppression and cancer: A comparison of risks in recipients of organ transplants and in HIV-positive individuals.

The comparison of cancers occurring excessively among HIV-infected and transplanted individuals may help to elucidate the relationship between immune surveillance, viral infections, and cancer. A longitudinal study was conducted on 2002 HIV-infected Italian subjects, 6072 HIV-infected French individuals, and 2878 Italian recipients of solid organ transplants. Standardized incidence ratios (SIR) and 95% confidence intervals (CI) were computed to quantify the risk for cancer, compared with the French and Italian general populations. The SIRs for all cancers were 9.8 (95% CI: 9.0-10.6) for HIV-infected individuals versus 2.2 (95% CI: 1.9-2.5) for transplant recipients. In both groups, most of the excess risk was attributable to virus-related cancers, such as Kaposi's sarcoma (KS; SIR = 451 in HIV-positive individuals, 125 in transplant recipients), non-Hodgkin's lymphoma (NHL; SIR = 62.1 and 11.1, respectively), and liver cancer (SIR = 9.4 and 4.1, respectively). Significantly increased SIRs for anal cancer and Hodgkin's lymphoma were found only among HIV-positive individuals. Among women younger than 40 years of age, a more than 10-fold increase in cervical cancer risk was found in both groups. Among HIV-infected individuals treatment with highly active antiretroviral therapies drastically reduced SIRs for KS and NHL only. These results show that HIV-infected individuals and transplant recipients share a similar pattern of cancer risk, largely due to virus-related cancers.

Langerhans cell histiocytosis in adults. Report from the International Registry of the Histiocyte Society.

Langerhans cell histiocytosis (LCH), characterised by the infiltration of one or more organs by large mononuclear cells, can develop in persons of any age. Although the features of this disease are well described in children, they remain poorly defined in adults. From January 2000 to June 2001, 274 adults from 13 countries, with biopsy-proven adult LCH, were registered with the International Histiocyte Society Registry. Information was collected about clinical presentation, family history, associated conditions, cigarette smoking and treatment, to assist in future management decisions in patients aged 18 years and older. There were slightly more males than females (143:126), and the mean ages at the onset and diagnosis of disease were 33 years (standard deviation (S.D.) 15 years) and 35 years (S.D. 14 years), respectively. 2 patients had consanguineous parents, and 1 had a family history of LCH; 129 reported smoking (47.1%); 17 (6.2%) had been diagnosed with different types of cancer. Single-system LCH, found in 86 patients (31.4%), included isolated pulmonary involvement in 44 cases; 188 patients (68.6%) had multisystem disease; 81 (29.6%) had diabetes insipidus. Initial treatment consisted of vinblastine administered with or without steroids, to 82 patients (29.9%), including 9 who had received it with etoposide, which was the sole agent given to 19 patients. 236 patients were considered evaluable for survival. At a median follow-up of 28 months from diagnosis, 15 patients (6.4%) had died (death rate, 1.5/100 person years, 95% Confidence Interval (95% CI) 0.9-2.4). The probability of survival at 5 years postdiagnosis was 92.3% (95% CI 85.6-95.9) overall, 100% for patients with single-system disease (n=37), 87.8% (95% CI 54.9-97.2) for isolated pulmonary disease (n=34), and 91.7% (95% CI 83.6-95.9) for multisystem disease (n=163). Survival did not differ significantly among patients with multisystem disease, with or without liver or lung involvement) 5-year survival 93.6% (95% CI 84.7-97.4) versus 87.5% (95% CI 65.5-95.9), respectively; P value 0.1). LCH in adults is most often a multisystem disease with the highest mortality seen in patients with isolated pulmonary involvement. It should be included in the differential diagnosis of disseminated or localised disease of the bone, skin and mucosa, as well as the lung and the endocrine and central nervous system, regardless of the age of the patient. A prospective international therapeutic study is warranted.

Prognostic value of pulmonary hypertension in patients with chronic interstitial lung disease referred for lung or heart-lung transplantation.

BACKGROUND: The purpose of this study was to identify precise and reliable prognostic parameters in patients affected by serious chronic interstitial lung disease, who were undergoing screening for lung or heart-lung transplantation. METHODS: Hemodynamic and respiratory function parameters of 67 patients (43 with idiopathic pulmonary fibrosis, 18 with histiocytosis X, and 6 with lymphangioleiomyomatosis) undergoing clinical screening for lung transplantation. RESULTS: Statistical analysis showed that hemodynamic and respiratory function parameters in patients affected by histiocytosis X and idiopathic pulmonary fibrosis were not related to survival time. Moreover, the degree of pulmonary hypertension showed no correlation between respiratory function parameters in all the groups of diseases examined. Patients affected with histiocytosis X, even with higher degrees of pulmonary hypertension, had a better survival rate (p < 0.0005) compared with patients with idiopathic pulmonary fibrosis. CONCLUSIONS: Hemodynamic and respiratory parameters obtained during the clinical screening for lung transplantation do not predict survival and cannot be used as prognostic indicators.

Isolated congenital complete heart block: longterm outcome of mothers, maternal antibody specificity and immunogenetic background.

OBJECTIVE: To assess the longterm outcome of mothers of children with isolated congenital complete heart block (CCHB), and the maternal specific immunoblot pattern and HLA antigens. METHODS: Fifteen mothers of 16 children with isolated CCHB were investigated; their followup extended up to 15.8 years on average after the index delivery. Anti-Ro and La antibodies were detected by counterimmunoelectrophoresis and ELISA; anti-Ro antibodies were studied by immunoblot. HLA typing was done using a microcytotoxicity test. RESULTS: One mother has systemic lupus erythematosus (SLE) before the index delivery. The other mothers developed only minor symptoms (arthralgia, dry eyes and photosensitivity) resembling primary Sjögren's syndrome more than classic lupus. All 15 mothers were anti-Ro and 9 were also anti-La positive, a mean of 12.5 years after the index delivery. Eight mothers reacted with the 52 kDa SSA(Ro) component, and 2 also with the 60 kDa SSA(Ro) component. The prevalence of the DR3 antigen and of the B44/DR5, DR3/DQ2 and A1/Cw7/B8/DR3/DQ2 haplotypes was significantly increased. CONCLUSION: The longterm outcome for the mothers of children with CCHB is more reassuring than generally assumed. All the mothers were anti-Ro positive by sensitive ELISA: Reactivity to the denaturated 52 kDa SSA(Ro) component seems characteristic of these mothers, who presented a particular immunogenetic background.

Isolated congenital complete heart block: longterm outcome of children and immunogenetic study.

OBJECTIVE: To assess the longterm cardiologic and immunologic outcome of children with isolated congenital complete heart block (CCHB) and their HLA antigens. METHODS: Sixteen children with isolated CCHB were investigated. HLA typing was done using a microcytotoxicity test. RESULTS: Three patients died (18.7%), one in utero (35 weeks), one 2 days after birth, and one at 6 years of age. The mean age of the 13 living children is now 18.3 years (range 2-34). Eight (50%) have been permanently paced for symptoms. No patient developed clinical symptoms or serological abnormalities suggesting immune disease. The A31 antigen was more prevalent, but one pair of HLA identical twins was observed, and only one had CCHB. CONCLUSION: Patients with isolated CCHB have significant cardiac mortality, and after a long followup many of them are paced to control symptoms, but in our small sample those who survive the perinatal period mostly lead a normal life. The longterm immunological outcome of these children seems good. CCHB is not related to a specific HLA pattern in affected children.

Immunocytochemical detection of progesterone receptors. A study in a patient with primary pulmonary hypertension.

Primary pulmonary plexogenic arteriopathy (PPPA) is one of the principal conditions in which pulmonary hypertension may be clinically unexpected. It occurs in the lung vessels in the absence of any demonstrable cause. Its high incidence in women of childbearing age combined with reports of disease following delivery of a child or assumption of oral contraceptives suggest that hormonal factors may play a role in the pathogenesis of PPPA. The suspicion that the pulmonary vascular lesions occurring in PPPA could represent the effect of a hormonal mediated vascular hyperreactivity prompted the evaluation of the steroid hormone receptor status on lung tissue obtained from a women suffering from this disease who had a double-lung transplantation. By the immunocytochemical method performed on formalin fixed, paraffin-embedded lung tissue, we showed the presence of progesterone receptors (PR) in the nuclei of the myofibroblasts forming the arterial obstructive intimal proliferations and of the spindle cells present in the walls of the plexiform lesions. To enhance the staining and to facilitate the observation, we used a microwave-based antigen unmasking technique. The lack of estrogen receptors and the presence of PR could have increased, in the case, the sensitivity of the pulmonary muscular arteries to vasoconstrictory compounds. We hypothesize that on this substrate of a presumptive steroid-mediated vasoconstriction the sequence of the histologic lesions characteristic of pulmonary vascular hypertensive disease could have developed.

Pulmonary hypertension secondary to thrombosis of the pulmonary vessels in a patient with the primary antiphospholipid syndrome.

Recurrent pulmonary emboli or microthromboses are hypothesized as possible causes of pulmonary hypertension in the antiphospholipid syndrome (APS), but thrombosis of the pulmonary vessels has been rarely documented. We describe the case of a 45-year-old Caucasian man affected by thrombocytopenia, recurrent deep venous thrombosis, recurrent pulmonary embolism and fatal chronic pulmonary hypertension (systolic pressure: 85 mm Hg). Anticardiolipin antibodies were highly positive, and the lupus anticoagulant was present. At autopsy, recent thromboses of small vessels were observed in the lung, with organized clots and recanalized channels. Furthermore, friable and firm vegetations and nodules were observed on the cusps of the mitral and tricuspid valves, intermingled with recent surface fibrinous thrombi. In the adrenals we found vascular thrombotic lesions similar to those in the lungs. The pathological lesions suggest pulmonary hypertension secondary to pulmonary arterial microthromboses. Moreover, this is the first documentation of tricuspid valve pathology in a patient with APS.

Selection and evaluation of recipients for heart-lung and lung transplantation: the Niguarda Hospital experience.

Between January 1989 and February 1993, 52 patients were evaluated at Niguarda Hospital for lung or heart and lung transplantation. Of the 35 that entered the waiting list, a total of 19 were transplanted (14 at other institutes before our surgical programme became operative, and 5 at our hospital). Recipient selection and evaluation criteria, and timing of transplantation in the different diseases are discussed.