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Founded by Richard C. Cabot Nancy Lee Harris, m.d., Editor Eric S. Rosenberg, m.d., Associate EditorJo-Anne O. Shepard, m.d., Associate Editor Alice M. Cort, m.d., Associate EditorSally H. Ebeling, Assistant Editor Christine C. Peters, Assistant Editor
From the Pulmonary and Critical Care Unit (B.D.M.) and the Departments of Radiology (G.F.A.) and Pathology (A.L.), Massachusetts General Hospital; and the Departments of Medicine (B.D.M.), Radi-ology (G.F.A.), and Pathology (A.L.), Har-vard Medical School — both in Boston.
Dr. Amy C. Sievers (Infectious Diseases): A 48-year-old man was seen in the orthope-dic clinic of this hospital because of cough, pain in the left shoulder, and a radio-graphically lucent lesion in the scapula.
The patient had been well until approximately 2.5 months earlier, when pain in the left shoulder developed, which was initially intermittent and then became con-stant. Two months before evaluation, a cough productive of greenish sputum de-veloped, without hemoptysis, chest pain, shortness of breath, fevers, chills, weight loss, or fatigue. A chest radiograph obtained at another hospital reportedly showed pneumonia and a possible lucency in the left scapula. Antibiotics were adminis-tered, and the cough improved but then recurred. Five days later, a bone scan report-edly showed two lesions with increased activity involving the posterior spine of the left scapula and the medial cortex of the right femoral shaft. Computed tomogra-phy (CT) of the chest, abdomen, and pelvis revealed a lucent lesion within the left scapular spine, with erosion of the cortical surface along the ventral aspect and an intact dorsal (posterior) cortex. There were numerous mildly enlarged mediastinal and bilateral hilar lymph nodes, as well as ill-defined lung nodules, an indetermi-nate lesion (5 mm in diameter) in the left hepatic lobe, three other cystic lesions (5 mm in diameter) within the liver, and apparent thickening of the wall of the cecum. A colonoscopic examination was reportedly normal.
Approximately 6 weeks before this evaluation, dual CT and positron-emission tomography (PET) performed after the administration of 18F-fluorodeoxyglucose (18F-FDG) reportedly showed a well-circumscribed lytic lesion, 13 mm in diameter, in the left scapular spine with marked 18F-FDG uptake (specific uptake value, ap-proximately 5.5 to 6), which was thought to be suspicious for a neoplasm. The PET–CT scan also showed hypodense nodules in the lower pole of the left lobe of the thyroid gland and in the left lobe of the liver and scattered lymph nodes (<1 cm in diameter) in the mediastinum, with no 18F-FDG uptake. Cytologic examination of a specimen from a CT-guided fine-needle aspiration biopsy of the scapular le-sion showed blood and scattered inflammatory cells and was thought to be nondi-agnostic.
Case 16-2010: A 48-Year-Old Man with a Cough and Pain in the Left Shoulder
Benjamin D. Medoff, M.D., Gerald F. Abbott, M.D., and Abner Louissaint, Jr., M.D., Ph.D.
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Magnetic resonance imaging (MRI) scans of the left shoulder and right femur, obtained at another facility after the administration of gado-linium, showed a lesion (23 mm by 14 mm) in the left scapular spine, which was isointense on T1-weighted images and hyperintense on T2-weighted images, with heterogeneous enhancement and ex-tension through the ventral cortex of the scapula and a periosteal reaction, soft-tissue component, and an intact posterior cortex. A sharply defined, gadolinium-enhancing lytic lesion within the cor-tex of the right distal femoral shaft showed a mild periosteal reaction and some associated cortical thickening. The patient was referred to the ortho-pedic clinic of this hospital.
The patient reported that the pain was located primarily in the region of the left scapular spine, occurred at rest, and awoke him at night. He de-scribed it as a constant aching and throbbing and gave it a score of 5 (on a scale of 1 to 10, where 10 is the most severe pain). The pain less-ened with rest and narcotic analgesia and in-creased when the patient lay on his side, raised his arms overhead, lifted objects, and moved his neck. He had no fever, chills, change in appetite or weight, or leg pain. He was right-handed, had a history of bipolar disorder, and had had an ap-pendectomy in the past. He had no known aller-gies to medications. Medications included oxy-codone as needed for pain, lamotrigine, lithium, and pantoprazole. He was divorced and worked in an office. He had smoked one to two packs of cigarettes per day for the past 3 years but more than two packs per day during the past several months. He did not drink alcohol or use illicit drugs. His father had died at 68 years of age from metastatic colon cancer, his mother was 83 years of age and had Paget’s disease, and a brother had diabetes mellitus.
On examination, the height was 175 cm and the weight 90.7 kg. The vital signs were normal. The patient was in mild distress because of pain in the left shoulder and posterior scapular area during active and passive motion; the range of motion was restricted when his arm was above the horizontal position. The spine of the left scapula was tender to palpation; sensation, strength, and pulses in both arms and legs and motion of the right shoulder and arm were nor-mal. The white-cell count was 13,000 per cubic millimeter (reference range, 4500 to 11,000), with a normal differential count, and the level of C-reactive protein was 11.7 mg per liter (reference
range, <8). Results were normal for measurements of platelets, erythrocyte sedimentation rate, glu-cose, plasma electrolytes, calcium, total protein, albumin, globulin, bilirubin, lactate dehydroge-nase, immunoglobulins, and urine Bence Jones protein; studies of serum protein electrophoresis and tests of renal and liver function were also normal. Two days later, a CT-guided fine-needle aspiration biopsy of the right femur was performed at this hospital; pathological examination of the biopsy specimen revealed inflammatory cells, stri-ated muscle, debris, and a few epithelioid histio-cytes and was thought to be nondiagnostic.
Six days later, the patient was admitted to this hospital. The white-cell count was 15,800 per cubic millimeter, with a normal differential count, and the level of C-reactive protein was 19 mg per li-ter; the remainder of the complete blood count was normal, as were serum levels of angiotensin-converting enzyme, antineutrophil cytoplasmic antibodies (ANCA), and vitamin D. A chest radio-graph revealed low lung volumes. An open exci-sional biopsy and curettage of the lesion of the left scapular spine were performed; cefazolin was administered before and after the surgery. Path-ological examination showed necrotizing granu-lomas and acute inflammation, features thought to be consistent with granulomatous osteomyeli-tis. Gram’s staining of a smear showed few mono-nuclear cells, very few polymorphonuclear leuko-cytes, and no organisms; specimens were cultured for bacteria, mycobacteria, and fungi and re-mained sterile.
The next day, an infectious-disease consultant obtained additional history. The patient reported having severe fatigue, sweats, myalgias, and anxi-ety for several weeks. A skin test for tuberculosis had been negative within the past year, and test-ing for antibodies to the human immunodefi-ciency virus (HIV) was reportedly negative 1 year earlier. The patient had traveled to Eastern Eu-rope and South America during the previous 16 years but had not been to rural areas or been ex-posed to animals recently. He reported no high-risk sexual activity, occupational exposures, or travel to the Midwest or southwestern United States. Tests for Coxiella burnetii, Treponema pallidum, Bartonella henselae, Bartonella quintana, and Burkhold-eria pseudomallei, and urinary histoplasma antigen were negative. He was discharged later that day.
Five days later, at a follow-up visit, the patient reported increased scapular pain. A radiograph of the left scapula showed a lytic lesion of the left
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scapular spine, with associated fracture. Tests of pulmonary function showed reduced single-breath carbon monoxide diffusing capacity (21.38 ml per minute per millimeter of mercury, or 68% of the predicted value) and decreased residual volume (0.94 liters, or 47% of the predicted value). During the next 3 days, increasing fatigue, malaise, weakness, sweats, myalgias, and scapular pain developed. He was readmitted to this hospital. The vital signs were normal. There was mild ery-thema surrounding the surgical incision on the left scapula, which was clean and dry, with its sutures in place; the remainder of the examina-tion was unchanged. An electrocardiogram was normal. Tests for brucella species and crypto-coccus were negative. The white-cell count was 15,000 per cubic millimeter, with a normal dif-ferential count. CT of the chest, abdomen, and pelvis showed multiple nodules (2 to 4 mm in diameter) and cystic lucencies throughout both lungs, lymph nodes in both axillae (up to 1.2 cm in diameter) and the abdomen (up to 1.7 cm in diameter), and a thyroid nodule (1.2 cm). Airborne precautions were instituted. Specimens of blood and sputum were cultured for bacteria, myco-bacteria, and fungi and remained sterile. Vanco-mycin and doxycycline were begun. Tests for respiratory viruses and antibodies to HIV were negative, as were multiple specimens of sputum stained for acid-fast bacilli; airborne precautions were stopped on the third day. Vancomycin was discontinued, and ceftriaxone and gentamicin were begun.
A diagnostic procedure was performed.
Differ en ti a l Di agnosis
Dr. Benjamin D. Medoff: May we review the imaging studies?
Dr. Gerald F. Abbott: A view of the left shoulder from a chest radiograph obtained on the day of the patient’s first admission to this hospital shows a sharply defined, radiolucent lytic lesion in the left scapula (Fig. 1A). A CT image from the PET–CT study, performed 6 weeks earlier, shows a sharply defined lytic lesion with a “punched-out” appearance (Fig. 1B). A PET study showed intense 18F-FDG uptake in the lesion (Fig. 1C). An unen-hanced axial CT scan of the distal shaft of the right femur, performed at the time of the CT-guided biopsy, shows a similar sharply defined lucent defect in the cortex of the femur (Fig. 1D).
A chest radiograph obtained on the patient’s
first admission to this hospital shows subtle, fine reticulonodular opacities in both lungs that ap-pear to spare the costophrenic sulci (Fig. 2A). An axial image from the chest CT performed on the second admission (Fig. 2B) shows small, irregu-lar pulmonary nodules that measure 2 to 3 mm in diameter. Several nodules appear to be cavitated, with small central areas of low attenuation, and some appear centrilobular in distribution. Small cysts of various sizes are also seen in both lungs. The small nodules and cysts predominantly in-volve the upper and middle zones of the lungs and appear to spare the lung bases and costo-phrenic sulci. This distribution is more apparent on a reformatted coronal CT image (Fig. 2C). Mediastinal or hilar lymphadenopathy and pleu-ral effusions were absent.
Dr. Medoff: This patient had a 3-month illness characterized by shoulder pain, cough, lytic bone lesions, and pulmonary nodules and cystic lesions. In formulating my differential diagnosis, my key considerations are the combination of bone and pulmonary disease, the pattern of the lung pa-renchymal and bone abnormalities, and the pa-tient’s smoking history. Disorders that affect both the lung and the bone are summarized in Table 1. The presence of pulmonary nodules and cysts that were predominant in the upper lobe, the sharp circumscription of the bone lesions, and the patient’s being a smoker are critical fac-tors in narrowing the differential diagnosis. In addition, the difficulty in making a diagnosis de-spite multiple bone biopsies and cultures reduces the likelihood of some of the possibilities.
Malignant tumors
The combination of pulmonary nodules and lytic bone lesions in a patient who smokes might lead to concern about the possibility of a primary lung cancer. However, multiple small nodules in the lung are atypical for this diagnosis, and one would expect bone-biopsy specimens to be diagnostic of a malignant tumor. Other cancers, such as mul-tiple myeloma,1 lymphoma, mastocytosis,2 and neuroendocrine tumors,3 uncommonly but occa-sionally present with lung and bone involvement. In this patient, I would expect the bone biopsy to be diagnostic.
Infections
The bone-biopsy specimen was suggestive of an infectious process. Many infections can involve the lung and bones simultaneously. The patient de-
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scribed cough with green sputum, chills, and sweats, which could be consistent with an acute infection, but the time course of his symptoms is strongly suggestive of a subacute or chronic pro-cess. Thus, we should consider infectious organ-isms that lead to chronic pneumonia and osteo-myelitis. Tuberculosis typically causes upper-lobe lung disease and can lead to nodules and cystic lesions. Bone and joint involvement occurs in 2% of tuberculosis infections.4 Thus, tuberculosis is a possible cause of this patient’s presentation, but the relatively mild systemic symptoms and the findings on chest CT make this diagnosis unlikely.
Chronic fungal infections can involve lung and
bone. In particular, 4% of patients with blastomy-cosis have involvement of the skeletal system.5-7
However, this patient had not traveled to areas where blastomycosis is endemic. He had traveled to South America, where paracoccidioidomycosis is endemic. This disease can cause pneumonia and osteomyelitis but usually affects immunocom-promised hosts.
Chronic bacterial infection with unusual organ-isms may present with lung and bone involvement. Symptoms resembling tuberculosis, chronic pneu-monia, and osteomyelitis can often present years after infection with Burkholderia pseudomallei (me-lioidosis).8,9 Similarly, infection with nocardia spe-
A B
DC
Figure 1. Images of the Left Shoulder and Femur.
A chest radiograph (Panel A) shows a sharply defined lucent lesion in the left scapula (arrow). A scan from combi-nation positron-emission tomography and CT performed 6 weeks earlier shows a sharply defined lytic lesion with a “punched-out” appearance (Panel B, arrow) and intense 18F-fluorodeoxyglucose uptake in the lesion (Panel C). An axial unenhanced CT scan of the distal shaft of the right femur obtained at the time of the CT-guided fine-needle aspiration biopsy (Panel D) shows a sharply defined lucent defect in the cortex of the femur. The lesion has a punched-out appearance, with margins that resemble those of the left scapular lesion.
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cies can cause lung nodules with cavitations and osteomyelitis.10 These are rare infections, how-ever, and there is nothing in the patient’s history that would favor these agents.
Sarcoidosis
The patient’s presentation and the difficulty in making a diagnosis despite multiple biopsies and cultures are strongly suggestive of a noninfectious inflammatory or idiopathic process. Although many such disorders can affect the lung and lead to diffuse nodular or interstitial disease, the num-ber of disorders that also affect the bones is sub-stantially more limited.
One of the more common forms of interstitial lung disease is sarcoidosis, a systemic granu-lomatous inflammatory disease that can affect almost any organ. In 90% of cases, it presents with pulmonary manifestations, with a typical pattern of hilar lymphadenopathy and interstitial infiltrates.11 Bone involvement occurs in 3 to 13% of cases and can appear as lytic or sclerotic dis-ease.12 The bone biopsy in this case showed granulomas, but they were necrotizing granulo-mas, whereas the granulomas of sarcoidosis are typically non-necrotizing. In addition, multiple lung nodules in the absence of prominent lymph-adenopathy are atypical in cases of sarcoidosis.
Systemic vasculitides, such as Wegener’s gran-ulomatosis, commonly involve the lung and can involve the bones, largely through the induction of bone infarcts. Pulmonary findings are usually more dramatic and lead to more severe symptoms. This patient’s negative serologic tests make these diagnoses unlikely.
Storage diseases
Another major category of interstitial lung dis-ease that can affect bone is lipid-storage diseases. Gaucher’s disease results from a genetic defi-ciency in the activity of the lysosomal enzyme β-glucocerebrosidase that leads to the accumula-tion of glucocerebroside in the lysosomes of macrophages. Over time, this and other storage disorders can lead to interstitial changes in the lung. However, the usual pattern on CT scans is patchy ground-glass opacities and reticulonodu-lar opacities, not the cysts and scattered nodules seen in this patient.13 Skeletal manifestations of storage disorders include a classic flask-shaped appearance of the long bones (due to cortical thin-ning) and osteosclerotic and osteonecrotic le-sions, unlike the well-defined lytic lesions in this
case.14,15 Furthermore, these disorders usually affect patients younger than this one and involve other organ systems in addition to the lung and bones. Thus, it does not seem likely that this pa-tient had a lipid-storage disorder.
A
B
C
Figure 2. Images of the Lungs.
A chest radiograph obtained at the time of admission to this hospital (Panel A) shows subtle, fine reticu-lonodular opacities in both lungs that appear to spare the costophrenic sulci. An axial CT scan of the chest (Panel B) shows small, irregular pulmonary nodules that measure 2 to 3 mm in diameter; some nodules ap-pear centrilobular in distribution. Several nodules ap-pear to be cavitating, and there are small central areas of low attenuation. Small cysts of various sizes are also seen in both lungs. The small nodules and cysts pre-dominantly involve the upper and middle zones of the lungs and appear to spare the lung bases and costo-phrenic sulci. This distribution of findings is more ap-parent on a reformatted coronal CT image (Panel C).
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Histiocytic disorders
The final category of diseases that I considered is the histiocytic disorders, since this patient’s bi-opsy specimen contained granulomas, which are composed of histiocytes. Histiocytic disorders are characterized by the accumulation of histiocytes in various tissues and include both reactive and neo-plastic conditions of histiocytes (macrophages) and dendritic cells.16-19 Two of these disorders deserve particular consideration.
Erdheim–Chester disease typically presents with skeletal disease and also involves the lung in 20 to 35% of cases.20,21 The disease usually affects middle-aged adults, and in patients with lung in-volvement, it presents with cough and dyspnea. Skeletal films typically show osteosclerotic and lytic lesions involving the long bones. Chest ra-
diographs of patients with lung disease usually show interstitial infiltrates, often with pleural dis-ease. A diagnosis of Erdheim–Chester disease is possible in this case, but the pattern of bone involvement in this patient is atypical, and the scattered nodules and cysts on chest CT are not characteristic of the disease.22,23
A final disease to consider is Langerhans’-cell histiocytosis (LCH). LCH is characterized by the accumulation of Langerhans’ cells in various or-gans and is often associated with inflammation and eosinophils.24,25 Langerhans’ cells are located in epithelial surfaces, such as the skin, where their primary function, after they migrate to regional lymph nodes, is to present foreign antigens to T cells, thus helping to initiate the adaptive im-mune response. LCH can involve bone and adja-cent tissues, including the pituitary gland, lungs, skin, lymph nodes, liver, spleen, and bone mar-row. Pulmonary LCH is rare, making up about 5% of cases of interstitial lung disease.20 More than 90% of cases of pulmonary LCH occur in adults who smoke.25 The disease can present with non-specific respiratory symptoms such as cough and dyspnea, but often patients are asymptomatic and the disease is detected only on routine imaging. Chest radiographs usually are suggestive of in-terstitial lung disease, and CT scans show nod-ules and cysts that are located predominantly in the upper lobes. Pulmonary-function tests can show a restrictive or an obstructive ventilation defect, or both. In 60 to 85% of patients, there is a reduction in the carbon monoxide diffusing capacity, as seen in this patient.25 Bone disease may occur and is characterized by destructive lytic lesions that occur most frequently in flat bones.24
Smoking-related lung disease
One final consideration in this case is the pa-tient’s history of smoking. Smoking is associated with the development of chronic obstructive pul-monary disease (COPD) and lung cancer, but it is also linked to a spectrum of related interstitial lung diseases (respiratory bronchiolitis, respira-tory bronchiolitis–associated interstitial lung dis-ease, and desquamative interstitial pneumonitis). These disorders occur sporadically among people who smoke, and they do not seem to have the same dose-related features that are seen in cases of COPD and lung cancer.26 These disorders usu-ally present with ground-glass opacities and do
Table 1. Selected Disorders That Can Involve Lungs and Bones.
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not have skeletal manifestations; thus, they are not considerations in this case. Pulmonary LCH, however, typically has nodular and cystic lesions with distribution in the upper lung field, as seen in this case.
Summary
In this patient with nodular and cystic lesions in the lungs, sharply defined lucent lesions in the bones on imaging studies, and a history of smok-ing, I think the most likely diagnosis is LCH with involvement of the lung and bones. In 10 to 40% of cases, the diagnosis can be made with the use of bronchoscopy with bronchoalveolar lavage and transbronchial biopsy.25 However, in this case, I suspect that the diagnostic procedure was a surgical lung biopsy by means of video-assisted thoracoscopic surgery, in view of the difficulties in making the diagnosis during the previous 3 months.
Dr. Nancy Lee Harris (Pathology): May we have the medical students’ diagnosis?
A Harvard Medical Student: The medical students based their differential diagnosis on several fea-tures of the case: the fact that the patient smoked, the presence of painful lytic bone lesions, the presence of lung lesions characterized by cystic lucencies in the upper lobes, the multiple nega-tive cultures and normal laboratory-test results, and the presence of granulomatous-appearing features on examination of the biopsy specimen. We thought that the diagnosis that best unified these features was LCH and that a transbronchial or open-lung biopsy should be performed.
Dr. Harris: Dr. Sievers, would you tell us what you were thinking and what you did to establish a diagnosis?
Dr. Sievers: An infectious process had been strongly suspected, but after the negative workup for infectious causes and the finding of features on chest CT that the radiologists thought were characteristic of pulmonary LCH, we favored that diagnosis as an explanation of both his lung and bone lesions. Before proceeding with video-assist-ed thoracoscopic surgery, we asked the pathology service to re-review the bone-biopsy specimen with this diagnosis specifically in mind.
Clinic a l Di agnosis
Langerhans’-cell histiocytosis of the lung and bone.
Dr . Benja min D. Med off’s Di agnosis
Langerhans’-cell histiocytosis involving lung and bone.
Pathol o gic a l Discussion
Dr. Abner Louissaint, Jr.: The scapular-biopsy speci-men submitted for pathological examination showed extensive necrosis, with prominent acute inflammation and collections of histiocytes, in-terpreted as necrotizing granulomas (Fig. 3A and 3B). The initial diagnosis was acute osteomyelitis with necrosis and granulomas. An infectious cause was considered probable, despite negative stains for microorganisms.
When the diagnosis of LCH was suggested by the radiologists, the slides were reexamined. It was then apparent that there were in fact sheets of histiocytic cells that were not forming discrete granulomas but, rather, had the appearance of a tumor (Fig. 3C). The cells had elongated, grooved nuclei and a higher nuclear-to-cytoplasmic ratio than typical macrophages, features that are sug-gestive of Langerhans’ cells. There were no eosino-phils. Immunohistochemical staining for CD1a and langerin, markers specific in this context for Langerhans’ cells, was positive (Fig. 3D and inset), which confirmed the diagnosis of LCH. The lack of eosinophils is unusual but can occur. The presence of extensive necrosis and neutro-phil accumulation is unusual in LCH and led to an initial diagnosis that was incorrect.
This case illustrates the difficulty of establish-ing the diagnosis of a histiocytic or dendritic-cell disorder. Histiocytes and dendritic cells are com-mon components of both infectious and nonin-fectious inflammatory processes, and histiocytic disorders and neoplasms may have a prominent inflammatory background. Thus, clinical corre-lation is essential, and the clinician should not hesitate to convey clinical suspicion of any histio-cytic disorder to the pathologist.
This patient has LCH involving bone and pre-sumably also lung, on the basis of imaging stud-ies and his smoking history, suggesting multi-system disease27 (Table 2). Approximately 5 to 15% of cases of pulmonary LCH are reported to have extrapulmonary involvement, most common-ly bone, as in this patient.28-30 The relationship
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between the pulmonary and the bone lesions in these cases is unclear. Pulmonary LCH is gener-ally thought to represent a reactive process in-duced by factors in cigarette smoke,28 and assays based on polymorphisms at loci such as the lo-cus of the human androgen receptor (HUMARA) gene have shown that most cases are polyclonal.29
LCH of bone and other extrapulmonary sites, in contrast, is generally considered to be a neoplasm of Langerhans’ cells,19 and lesions have been shown by HUMARA gene assays to be clonal in most cases.31 However, clonal outgrowth may arise from some polyclonal pulmonary LCH le-sions.29 Therefore, it is possible that one of the reactive pulmonary lesions in this patient gave rise to a clone that was able to grow indepen-dently of the pulmonary microenvironment and produce bone lesions. Alternatively, the primary
lesion in this patient could have been in the bone, and the neoplastic Langerhans’ cells could have been recruited to and proliferated in the lung because of the cytokine environment created by smoking. Finally, both may have arisen from a common circulating precursor cell, the existence of which has been suggested.32,33
Dr. Harris: Dr. Medoff, how would you treat this patient?
Dr. Medoff: The key step in the management of this disorder is for the patient to stop smoking, which in many patients will cause the disease to stabilize or even regress. Some patients have pro-gressive disease, so it is important to monitor the patient’s lung function. For progressive disease, the next step would be a trial of corticosteroids, although I know of no randomized trials that show benefit from such therapy. Bone lesions
A B
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Figure 3. Photomicrographs of the Scapular-Biopsy Specimen.
There is extensive necrosis (Panel A, hematoxylin and eosin) and prominent acute inflammation. At higher magnifi-cation, neutrophils and histiocytes are seen in a background of necrosis (Panel B, hematoxylin and eosin). Sheets of cells are seen (Panel C, hematoxylin and eosin), with elongated, grooved nuclei and a higher nuclear-to-cytoplasmic ratio than is typical of macrophages, features suggestive of Langerhans’ cells. Immunohistochemical stains for CD1a (Panel D) and langerin (inset) are positive, confirming the diagnosis of Langerhans’-cell histiocytosis.
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may be treated with local injections of corticos-teroids, and surgical excision, which was per-formed in this case, can be curative.
Dr. Patrick J. Troy (Pulmonary and Critical Care Medicine): After the diagnosis of LCH was estab-lished, we counseled the patient on the strong association between smoking and pulmonary LCH. The patient was amenable to smoking cessation, which he was able to accomplish on his own, without pharmacologic therapy. On follow-up ap-proximately 3 months after his discharge, he re-ported lessening of his exertional dyspnea and fa-tigue. Follow-up pulmonary-function tests showed complete normalization of the carbon monoxide diffusing capacity.
Dr. Abbott: A follow-up CT study performed 3 months after smoking cessation showed almost complete resolution of the small nodules and cysts that had previously been seen (Fig. 1A in the Sup-plementary Appendix, available with the full text of this article at NEJM.org). A follow-up radio-graph of the left shoulder showed evidence of callus formation and healing of the lytic lesion and the associated fracture (Fig. 1B in the Sup-plementary Appendix). A follow-up radiograph of the femur 9 months after smoking cessation (Fig. 1C in the Supplementary Appendix) showed mild cortical thickening along the medial diaphysis, a feature consistent with healing of the lytic lesion; repeat CT of the femur has not been performed.
Dr. Harris: I was not able to find reports of healing of bone lesions of LCH after smoking ces-sation, although both pulmonary and solitary bone lesions of LCH may resolve spontaneously.27 In this case, it seems likely that the bone and lung lesions were clonally related and depended on
the same stimuli for survival and proliferation, whether one arose from the other or both arose from a common precursor.32,33
A nat omic a l Di agnosis
Langerhans’-cell histiocytosis of bone and lung.
This case was presented at the Medical Case Conference, Sep-tember 18, 2009.
No potential conflict of interest relevant to this article was re-ported. Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
We thank Drs. Ronald Jaffe (Department of Pathology, Uni-versity of Pittsburgh, Pittsburgh), Carl E. Allen and Kenneth L. McClain (Department of Pediatrics, Texas Children’s Cancer Center, Baylor College of Medicine, Houston), Thomas V. Colby (Department of Pathology, Mayo Clinic, Scottsdale, AZ), and Robert Vassallo (Department of Medicine, Mayo Clinic, Roch-ester, MN) for contributing to our attempts to understand the biology of the patient’s disease.
Table 2. Clinical Categories of Langerhans’-Cell Histiocytosis.*
Category Common sites
Unisystem
Unifocal (single site) BoneSkin
Lymph node
Multifocal (multiple sites within one organ system)
Multisystem
BoneSkinLung
Skin, bone, liver, spleen, bone marrow (i.e., Letterer–Siwe disease, rare in adults)
Lung with extrapulmonary involvement, usually bone or skin (more common in adults than in children)
* Data are from Favara et al.,16 Ladisch and Gadner,27 and Vassallo et al.28
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Watts HG, Lifeso RM. Tuberculosis of 4. bones and joints. J Bone Joint Surg Am 1996;78:288-98.
Bradsher RW. Clinical features of 5. blastomycosis. Semin Respir Infect 1997; 12:229-34.
Chapman SW, Lin AC, Hendricks KA, 6. et al. Endemic blastomycosis in Missis-sippi: epidemiological and clinical stud-ies. Semin Respir Infect 1997;12:219-28.
Pappas PG. Blastomycosis in the im-7. munocompromised patient. Semin Respir Infect 1997;12:243-51.
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Lantern Slides Updated: Complete PowerPoint Slide Sets from the Clinicopathological Conferences
Any reader of the Journal who uses the Case Records of the Massachusetts General Hospital as a teaching exercise or reference material is now eligible to receive a complete set of PowerPoint slides, including digital images, with identifying legends, shown at the live Clinicopathological Conference (CPC) that is the basis of the Case Record. This slide set contains all of the images from the CPC, not only those published in the Journal. Radiographic, neurologic, and cardiac studies, gross specimens, and photomicrographs, as well as unpublished text slides, tables, and diagrams, are included. Every year 40 sets are produced, averaging 50-60 slides per set. Each set is supplied on a compact disc and is mailed to coincide with the publication of the Case Record.
The cost of an annual subscription is $600, or individual sets may be purchased for $50 each. Application forms for the current subscription year, which began in January, may be obtained from the Lantern Slides Service, Department of Pathology, Massachusetts General Hospital, Boston, MA 02114 (telephone 617-726-2974) or e-mail [email protected].
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