An integrated clinical approach to diffuse cystic lung diseases

Lymphangioleiomyomatosis and Langerhans cell Histiocytosis are two different diseases that can involve the lungs, with unknown etiology and origin. Both are rare, present a similar radiological pattern (multiple nodules and cysts in the lungs) and may have a similar clinical presentation, with progressive dyspnea, hemoptysis, pneumothorax and a variable course usually culminating in respiratory failure. Due to these similarities a differential diagnosis may be difficult in some instances. This review underlines differences in epidemiology, pathogenesis and prognosis that could assist clinicians in making a differential diagnosis of these rare and severe pulmonary diseases.     

Atypical sarcoidosis masquerading as neutropenia

Sarcoidosis is a systemic granulomatous disease of unknown etiology. Gastrointestinal involvement in sarcoidosis is rare and so are its hematological manifestations. We report an unusual case of sarcoidosis with isolated gastric involvement and concomitant B12 and iron deficiency, leucopenia and severe neutropenia. The diagnosis of GI tract sarcoidosis is difficult and other causes of GI tract granulomas should be excluded. Patients can have unusual manifestations like B12 deficiency and one should be aware of this possibility. Careful follow-up and frequent reevaluation of the patient may be a sound strategy in equivocal cases with unusual presentation.     

Diffuse interstitial pneumonitis after pulmonary irradiation for metastatic Wilms' tumor. A report from the National Wilms' Tumor Study

To evaluate the frequency, etiology, and outcome of diffuse interstitial pneumonitis after treatment of children with Stage IV (favorable histologic type) Wilms' tumor using whole-lung and abdominal radiation therapy, and combination chemotherapy, all cases reported in such patients entered on National Wilms' Tumor Study 3 were reviewed. Diffuse interstitial pneumonitis was reported in 13.0% of patients. The etiology was varicella, one patient; Pneumocystis carinii, three patients; and unknown, 15 patients. The time elapsed after the completion of whole-lung irradiation did not distinguish those patients with pneumonitis due to P. carinii from those with pneumonitis of unknown etiology. All three children with pneumonitis due to P. carinii survived the episode, whereas only four of 15 (27%) patients with pneumonitis of unknown etiology survived the episode. Management of Wilms' tumor patients who develop diffuse interstitial pneumonitis after whole-lung irradiation should include a diagnostic procedure known to be sensitive for the diagnosis of P. carinii infection.     

Lymphangioleiomyomatosis: a case report and review of the literature

Lymphangioleiomyomatosis, a rare disease of unknown etiology that is seen almost exclusively in women of childbearing age, generally presents with features of pulmonary involvement. It may be associated with tuberous sclerosis. Its clinical pulmonary manifestations vary from simple cough to the development of recurrent pneumothorax, hemoptysis, and even complicated pleural effusions. Progressive dyspnea develops as the disease evolves. Most patients eventually require lung transplant. This wide array of symptoms and signs makes the differential diagnosis extensive, and the clinician must be familiar with this disorder to arrive promptly to the correct diagnosis. Here we report a case of a 35-year-old woman with a history of pleuritic effusion with associated dyspnea before being diagnosed with lymphangioleiomyomatosis. A review of the literature pertinent to this case is also provided.     

Primary intracranial plasma cell granulomas presenting as malignant neoplasms

Plasma cell granuloma (PCG) is an uncommon non-neoplastic mass lesion of unknown etiology. It is characterized by a polyclonal proliferation of chronic inflammatory cells, mostly mature plasma and other mononuclear cells. PCGs arising in the central nervous system are particularly rare. We report two additional cases of intracranial PCG exclusively involving the brain parenchyma. A 47 year-old woman, presenting with partial motor seizures and fluent aphasia, underwent complete excision of a well-demarcated, enhancing left parietal mass. The second patient was a 56 year-old man presenting with headaches and right-sided weakness who underwent stereotactic biopsy of an ill-defined, heterogeneously enhancing lesion in the left basal ganglia. Immunohistochemical analysis of surgical specimens showed polyclonal plasma cells and mature lymphocytes but no etiological agent. A histopathologic diagnosis of intracranial PCG was made in both cases. PCG should be part of the differential diagnosis of enhancing mass lesions of the brain. The etiology and natural history of these tumor-like lesions is not fully understood. Complete surgical excision appears to be curative. Lesions where total resection is not possible may benefit from adjuvant treatment including corticosteroids and possibly radiation therapy.     

Growth of rhabdomyosarcoma colonies from pleural fluid.

Pleural fluid from a child previously treated for rhabdomyosarcoma produced colonies in vitro. Cells from these colonies appeared to have the light and electron microscopic appearance of rhabdomyosarcoma cells. In this case, the malignant nature of the effusion had been suspected because of the patient's previous history; however, this technique may prove useful in the diagnosis of effusion of unknown etiology.     

Drug-induced pneumonitis: the role of methotrexate

Methotrexate (MTX) is a folate antagonist used in several chronic inflammatory and neoplastic conditions. Pulmonary toxicity occurs in 0.5% to 14% of patients receiving low-dose MTX. Manifestations of pulmonary toxicity are protean and include parenchymal inflammation, pneumonia, airway hyperreactivity, air trapping and possibly neoplasm. We performed an exhaustive review of the English literature and identified 189 cases of methotrexate-induced pneumonitis (MIP). Rheumatoid arthritis (RA) was the most frequent underlying disease. In most patients, symptoms present subacutely with progression over several weeks. Most patients present with dyspnea, dry cough, fever, and bibasilar crackles. Peripheral eosinophilia has been cited in one third of cases. The chest radiograph may be normal, but more commonly reveals bilateral interstitial or mixed, interstitial and alveolar infiltrates with a predilection for the bases. Chest computed tomography (CT) scans demonstrate ground-glass opacities, interstitial infiltrates, septal lines or widespread consolidation. Pulmonary function studies reveal a restrictive ventilatory defect and/or impaired gas exchange. Bronchoalveolar lavage (BAL) may be helpful in ruling out an infectious etiology and in supporting the diagnosis of MIP. Cellular interstitial infiltrates, granulomas, fibrosis, atypical epithelial cells, and diffuse alveolar damage (DAD) are the main histologic features. Once MIP is suspected, the MTX should be withdrawn. Corticosteroids may accelerate resolution and are recommended in severe or fulminant cases. The prognosis of MIP is usually favorable, but occasionally the outcome may be fatal.     

Leukocytosis and large cell lung cancer. A frequent association

In a retrospective study of 105 patients with non-small cell lung cancer during a 5-year period, 43 had leukocytosis. In 19 of the 43 patients, no clear cut etiology for the leukocytosis was apparent and it was attributed to the tumor itself. In these 19 patients, absolute neutrophilia was detected in 13, eosinophilia was present in three, and eleven exhibited concomitant thrombocytosis. Tumor-associated leukocytosis occurred predominantly, and eosinophilia exclusively, in patients with large cell pulmonary neoplasms. These results suggest an unusual myeloproliferative stimulus in this type of cancer. It may result from tumor cell production of hemopoietic growth factors such as granulocyte-macrophage colony-stimulating activity; however, additional studies are needed to elucidate the underlying mechanism(s), and to determine whether this is a peculiar characteristic of the cells that comprise large cell undifferentiated carcinoma of the lung.     

Oral malignant melanoma: a review of the literature

Primary oral malignant melanoma (OMM) is a rare neoplasm, accounting for 0.5% of all oral malignancies. The etiology is unknown; tobacco use and chronic irritation may play some role. Clinically, OMM may mimick other pigmented lesions. A biopsy is required in order to establish the diagnosis. The reported risk of malignant cells spreading during invasive procedures and factors such as size of the lesion or anatomical limitations, may influence the diagnostic surgical procedure. Therapy of OMM is commonly based on surgical excision of the primary tumour, supplemented by radiotherapy, with chemotherapy and immunotherapy serving as adjuncts. Prognosis is poor, with a 5-year survival rate of approximately 15%.     

A case of smouldering mastocytosis with peripheral blood eosinophilia and lymphadenopathy

Systemic mastocytosis (SM) is a clonal hematologic disease showing abnormal growth and accumulation of mast cells (MC) in visceral organs with or without skin involvement. The clinical course in SM is variable. In fact, indolent and aggressive variants have been described. In addition, SM patients may acquire an associated hematologic clonal non-MC lineage disease (AHNMD). In some cases, hematologic parameters are indicative of slowly progressing SM although the clinical course remains indolent over years. These cases have been referred to as smouldering SM. We report on a smouldering patient presenting with typical skin lesions, hypercellular marrow with focal MC aggregates, persistent leukocytosis (20,000-30,000/microl) with eosinophilia (5-10%), marked lymphadenopathy, and splenomegaly. The C-KIT mutation Asp-816-Val confirmed the diagnosis of SM. The clinical picture remained stable during an observation period of 10 years without signs of progression to an AHNMD or a high grade MC disease. These data show that some patients with SM can remain in a clinically indolent smouldering state over years even when presenting with marked eosinophilia and lymphadenopathy.     

特殊T淋巴母细胞淋巴瘤一例诊治并文献复习

目的 探讨伴嗜酸性粒细胞增高的髓淋系肿瘤(FIP1L1-PDGFRα重排型)的正确诊断和治疗.方法 报道1例伴嗜酸性粒细胞增高的髓淋系肿瘤(FIP1L1-PDGFRα重排型)患者的诊治过程,并进行相关文献复习.结果 该患者根据淋巴结病理诊断为典型的T淋巴母细胞淋巴瘤,经全面分析和检查正确诊断为伴嗜酸性粒细胞增高的髓淋系肿瘤(FIP1L1-PDGFRα重排型),并经低剂量伊马替尼治疗获得快速深度缓解.结论 伴嗜酸性粒细胞增高的髓淋系肿瘤(FIP1L1-PDGFRα重排型)为罕见的血液肿瘤,虽然病理诊断是淋巴瘤诊断的金标准,但有时需要综合考虑,全面分析临床情况,正确看待病理结果,避免误诊、误治.     

Secondary cancers after a lung carcinoid primary: a population-based analysis

Carcinoid tumors of the lung were first described in 1937, yet little is known about their etiology. The aim of the present investigation was to determine if there was excess risk of secondary cancers in a population-based sample after a lung carcinoid tumor diagnosis which may provide insight to the etiology. Subjects were 1882 cases diagnosed with carcinoid tumors of the lung between 1988 and 2000 whose information was obtained from the Surveillance, Epidemiology and End Results (SEER) Program database. Standardized incidence ratios were calculated by dividing the observed number of second primary cancers by the expected number of cancers. Excess risk of breast cancer was seen following diagnosis of a carcinoid tumor (SIR=1.80 95% CI 1.22-2.55). When stratified by time after diagnosis, excess risk of breast cancers in women was seen in the first 5 years after carcinoid diagnosis (SIR=1.68 95% CI 1.08-2.50) but fewer than expected breast cancers were diagnosed greater than 5 years after carcinoid diagnosis (SIR=0.29 95% CI 0.09-0.68). Prostate cancers also occurred 2.8 times more often than expected (95% CI 1.66-4.43), with risk being elevated only in the first 5 years post-carcinoid diagnosis. Development of lung carcinoids may be the result of genetic predisposition or environmental exposures, particularly those that are hormonally related. The role of genetics and sex hormones in lung carcinoid development, as well as the identification of other risk factors, should be explored.     

Acute nonlymphocytic leukemia with marrow eosinophilia and chromosome 16 abnormality: a report of 18 cases

This article reports 18 cases of acute nonlymphocytic leukemia (ANLL) and abnormal chromosome 16. Thirteen had the same hematological pattern at diagnosis, i.e., peripheral blood hyperleukocytosis with high percentage of monocytes and blast cells, and bone marrow showing three different cell populations: (a) myeloblasts, (b) monocytes and promonocytes, and (c) abnormal eosinophils. In these cases the diagnosis was acute myelomonocytic leukemia with bone marrow eosinophilia, as described. However three other cases were of the M5 type and two others of the M2 type, all showing an abnormal eosinophilia in their bone marrow. All cases showed an abnormal chromosome 16 in the bone marrow cells: inv (16) in 13 cases, t (16;16) in two, del (16) in one of poor quality, and in two other translocations involving band 16q22. In one case the inv (16) was found in a subclone, indicating that it could be a secondary cytogenetic defect. Five patients died soon after diagnosis; the other 13 had a median complete remission duration of 8 months. The central nervous system was frequently involved upon relapse. We do not support the hypothesis that patients with M4-Eo ANLL and chromosome 16 abnormality have a favorable prognosis.     

Treatment for cancer-related fatigue: an update

Cancer-related fatigue is now a recognized phenomenon with an established diagnosis. Fatigue is the most common symptom experienced by cancer patients and in many cases, the challenge of alleviating its severity is daunting for the clinician. Occasionally, the clinician may be fortunate and discover a reversible cause of fatigue for which there is a readily available treatment. Most of the time, however, the etiology of cancer-related fatigue is multifactorial or treatment-related with unknown pathophysiologic abnormalities and the clinician must resort to a variety of modalities to attempt to relieve the fatigue. Research of cancer-related fatigue treatment is in its infancy and future clinical trials examining the effects of various pharmacologic and nonpharmacologic therapies for cancer-related fatigue are needed. The development of effective therapies for the treatment of cancer-related fatigue could profoundly affect the lives of many cancer patients.     

Eosinophilia associated with adult T-cell leukemia/lymphoma

Eosinophilia is associated with a number of disorders including malignancies. A patient is described who had eosinophilia associated with adult T-cell leukemia/lymphoma (ATL) induced by human T-lymphotropic virus type I (HTLV-I). Both tissue and peripheral blood eosinophilia and high titers of HTLV-I antibody were present. The eosinophilia was most likely caused by the malignant cells producing one or more lymphokines. The patient has achieved a durable complete remission from combination chemotherapy. Because durable remissions in ATL are rare with any known therapy and eosinophilia has not previously been associated with ATL, it is possible that the tumor in this patient was derived from a T-cell subset not usually transformed by HTLV-I. ATL is another malignancy now known to cause eosinophilia.     

Severe eosinophilia as a manifestation of acute graft-versus-host disease

Significant peripheral eosinophilia in association with acute graft-versus-host disease (GVHD) is rare. Here we report a case of eosinophilia in a 30-year-old woman with relapsed acute myelogenous leukemia after an allogeneic bone marrow transplant who was treated with donor lymphocyte infusion (DLI). A month after the DLI, she developed a pruritic erythematous rash, hepatic enzyme elevations and eosinophilia that peaked at 23,300 cells/mm(3). A diagnosis of acute GVHD was made and the patient was treated with corticosteroids with a resolution of all of the aforementioned findings. The authors suggest that eosinophilia in a bone marrow transplantation patient should raise suspicion of GVHD.     

Adult intussusception secondary to an ileum hamartoma

Intussusception is a rare condition in the adult population.However,in contrast to its presentation in children,an identifiable etiology is found in the majority of cases.Clinical manifestations of adult intussusception are non-specific and patients may present with acute,intermittent or chronic symptoms,predominantly those of intestinal obstruction.A 27-year-old male patient with recurrent abdominal pain secondary to intussusception is herein reported.The clinical presentation and ultrasonographic findings led to the diagnosis.At laparotomy,an ileal hamartoma was found as the lead point of the intussusception.Surgical management and histopathologic studies are described.A recurrent intestinal obstruction and classic ultrasound findings may lead to the diagnosis of intussusception but surgical exploration remains essential.The principle of resection without reduction is well established.     

Breast cancer and organochlorines: a marker for susceptibility?

The incidence of breast cancer is increasing and despite extensive research efforts, the etiology of this disease is largely unknown. Most women exhibit no known risk factors except for their age and sex. It has recently been postulated that the increased breast cancer incidence might be attributed to exposure to environmental carcinogens such as the organochlorine compounds. In this article, the scientific literature with respect to this possibility is reviewed and alternative hypotheses, which may in part explain the possible role of organochlorine compounds in the etiology of breast cancer, are presented.     

Gastric remnant carcinoma.

One hundred cases of gastric carcinoma at The New York Hospital-Cornell Medical Center included 7 cases of gastric remnant carcinomas, which were analyzed and compared with prior reports in the literature. Gastric remnant carcinoma is a distinct entity, noted in greatest incidence beginning approximately 15 years after surgery for benign gastric disease. Although the etiology is unknown, the high incidence of bile reflux and concomitant existence of histologic change may account for a premalignant environment in which the stomach assumes some absorptive function. Such new activity may result in the influx of potentially carcinogenic compounds and subsequent tumor development. Early diagnosis of remnant carcinoma following gastric surgery is important to improved prognosis, and endoscopic followup is recommended for all such patients beginning 10-15 years postoperatively.