Metastatic Angiosarcoma of the Scalp Presenting with Cystic Lung Lesions: A Case Report and Review of Cystic Lung Diseases

Abstract

Introduction

Angiosarcomas are rare, malignant vascular tumors that affect endothelial cells of blood vessels. Angiosarcomas most commonly occur on the scalp or face of elderly individuals and are highly aggressive, with a 5-year survival rate below 15%. Cutaneous angiosarcomas often metastasize to the lung, where they can present with cystic lesions, solid lesions, pneumothorax, and/or hemothorax.

Case Presentation

We report the case of an 83-year-old woman who presented with a scalp lesion, which was initially thought to be caused by scalp trauma but was later found to be an angiosarcoma. She initially refused any therapy for the tumor. She returned several months later with a cough and shortness of breath and was found to have multiple pulmonary cysts. She was treated with paclitaxel, but her tumor did not respond to the therapy and she died 2 months later.

Discussion

We discuss the common presentation of cutaneous angiosarcomas and their tendency to metastasize to the lung and present as cystic lesions. We also review the common conditions that can cause cystic changes in the lungs.

INTRODUCTION

Angiosarcomas are rare, malignant vascular tumors that affect endothelial cells of blood vessels.¹ They account for less than 2% of soft-tissue sarcomas and less than 1% of all head and neck cancers.^1,2 Angiosarcomas can occur in any part of the body; however, they most commonly occur on the scalp or face of elderly individuals.² These tumors are highly aggressive, with a 5-year survival rate of less than 15%.³ They spread rapidly through the skin, metastasize early, and tend to recur after treatment.¹ Cutaneous angiosarcomas often metastasize to the lung, where they can present with cystic lesions, solid lesions, pneumothorax, and/or hemothorax.³

CASE PRESENTATION

Presenting Concerns

An 83-year-old woman visited her primary care physician for evaluation of a tender, purple lesion on her scalp. She had been in good health until about 5 months earlier, when she recalled hitting the top of her head on a nectarine tree in her yard, causing a small wound to her scalp. The wound seemed to heal, but then 2 months later, she hit the same spot on her scalp (on the same branch of the nectarine tree); however, this time the wound failed to heal. She sought care from her primary care physician, who referred her to a head and neck surgeon.

At her appointment with the surgeon 2 days later, the wound was inspected and no foreign body was identified. A fluid collection was aspirated. She was reevaluated 13 days later, and the wound was deemed to be healing well.

Three months later, she visited her primary care physician again, this time for evaluation of multiple lesions on her scalp. She was referred back to the head and neck surgeon and was seen the same day in the surgeon’s clinic. On examination, multiple lesions were noted on the scalp, described as erythematous weeping lesions, with the largest being 3 cm × 4 cm. This lesion underwent biopsy, and the pathologic findings revealed an angiosarcoma. She was referred to an oncologist and was offered treatment with chemotherapy and radiation therapy. The patient refused any therapy. Staging computed tomography (CT) of the chest, abdomen, and pelvis was done, but the scans did not reveal any evidence of metastasis.

Three months later, she presented to the Emergency Department (ED) with shortness of breath. Chest radiographic findings were unremarkable. She received albuterol, with subsequent improvement in her symptoms, and was then discharged home. Two weeks after her ED visit, the patient developed herpes zoster and was prescribed acyclovir. She was seen again in the ED three weeks later for dyspnea this time requiring admission to the hospital for treatment of a suspected pneumonia. A chest CT (Figure 1) demonstrated cystic lung lesions characteristic of metastatic angiosarcoma and a left pleural effusion.

Figure 1.

Computed tomography scan of the patient’s lungs demonstrating multiple bilateral cystic lesions and a left pleural effusion.

Therapeutic Interventions and Treatment

The patient followed-up with her oncologist and a radiation oncologist. She was offered therapy with radiation to the scalp and paclitaxel. She agreed to both therapies and received fractionated doses of 2700 cGy of local radiation to the scalp and weekly paclitaxel therapy.

After one month of chemotherapy, she returned to the ED with chest pain and shortness of breath. She was found to have a non-ST-segment elevation myocardial infarction. A CT of the chest was repeated (Figures 2 and 3), which demonstrated multiple new lung lesions, a small right pneumothorax, and a left pleural effusion. A left thoracentesis was performed, and cytologic analysis yielded negative results.

Figure 2.

Computed tomography scan of the patient’s lungs taken two months after the image in Figure 1 and after one month of paclitaxel chemotherapy. There are now multiple new pulmonary nodules, some of which are becoming cystic.

Figure 3.

Computed tomography scan of the patient’s lungs demonstrating multiple right lower lobe nodules and a new right pneumothorax.

Follow-up and Outcomes

Because of progression of her lung disease despite chemotherapy, the patient elected for hospice care. A pleural drainage catheter (PleurX, Becton, Dickinson and Co, Franklin Lakes, NJ) was placed two weeks later given recurrent left pleural effusion. The patient was again hospitalized a month later because of shortness of breath and respiratory failure requiring bilevel positive airway pressure. This treatment was done only briefly because the patient decided to forgo any further treatment. She died that same day. See Table 1 for a timeline of the case.

Table 1.

Timeline of the case

Time	Presentation and therapies
0 mo	Patient hit top of scalp on nectarine tree
2 mo	Hits scalp again on nectarine tree
5 mo	Sought care from primary physician for nonhealing scalp lesion
5 mo, 2 d	Seen by head and neck surgeon
5 1/2 mo	Recheck by head and neck surgeon; wound appeared to be healing
8 1/2 mo	Sought care from primary physician for multiple scalp lesions; seen same day by head and neck surgeon and lesions biopsied (positive for angiosarcoma)
8 3/4 mo	Seen by oncologist; refused any therapy
12 mo	Seen in ED because of dyspnea; treated with albuterol and symptoms improved
12 1/2 mo	Developed Herpes zoster (treated)
13 mo	Seen in ED for dyspnea; noted to have new cystic lung lesions; seen by oncologist and started on local radiation and chemotherapy
14 mo	Seen in ED, had NSTEMI; multiple new lung lesions seen as well as larger left pleural effusions
15 mo	Pleural catheter placed because of recurrent left effusion
16 mo	Presented to ED in acute respiratory failure; elected to have no further therapy; died that day

ED = Emergency Department; NSTEMI = non-ST-elevation myocardial infarction.

DISCUSSION

Angiosarcomas are rare malignant tumors, which are of vascular or lymphatic endothelial cell origin; they constitute approximately 2% of all soft-tissue sarcomas.^2,3 They can occur at any age, but they are most common in elderly individuals and usually present on the scalp or face.³ They can present with a variety of clinical features but most commonly present as dark-purple, bluish, or red lesions, which may be nodular or plaque-like.⁴ They can ulcerate and often bleed after minor trauma, such as combing hair.⁴ The tumors can be difficult to diagnose in their early stages because their appearance may suggest a nonneoplastic process or they can be hidden under hair on the scalp. Initially, these tumors tend to spread locally and then often metastasize to lymph nodes, with the lungs being the most common distant site of metastases.¹

In the largest series to date of cutaneous angiosarcomas (434 cases over 34 years of surveillance), there was a predominance in men, with a mean age of 73 years, and most tumors began in the head and neck.² The survival rates were disparate depending on the age at which the tumor presented. Those patients whose age was younger than age 50 years had a 10-year survival rate of 72%, whereas patients who were older than age 50 years had a 10-year survival rate of 37%.² Also, the site at which the tumor originated had profound significance for survival rates; tumors arising in the trunk had a 10-year survival rate of 75%, whereas tumors that arose in the head and neck had a 10-year survival rate of only 14%.² Once the tumor metastasizes, the prognosis is very poor, with one series reporting a 4-month survival after the appearance of lung metastases.³ Indeed, our 83-year-old patient with an angiosarcoma of the scalp had a very poor prognosis, particularly after the appearance of lung metastases. Usually, there are no predisposing causes, although angiosarcomas have been linked to chronic lymphedema; arteriovenous fistulas; foreign bodies; and previous exposure to radiation, arsenic, or polyvinyl chloride.^1,2,4 Diagnosis requires a high suspicion for the disease and subsequent biopsy of the suspected lesion.

Effective treatment of the disease has yet to be clearly established. The mainstay of treatment is surgery with wide excision of the lesion, in an attempt to achieve tumor-free margins, and adjuvant radiotherapy.^1,3,5 Multifocal and widespread lesions are often treated with radiation therapy in cases in which surgery is not an option; however, results in these cases are often suboptimal.^3,4 In most cases, the preferred treatment of choice is a multimodal approach with a combination of surgery and radiotherapy.⁵ Other treatment options that have been studied include chemotherapy and immunotherapy.³ A number of chemotherapy agents have been tried with limited success, particularly with unresectable tumors, although recent reports suggest that there may be a role for paclitaxel.⁵ Our patient received paclitaxel and did not appear to benefit from this therapy.

Review of Common Cystic Lung Diseases

Cysts are defined as round, circumscribed spaces surrounded by a thin wall (often < 2 mm) of fibrous or epithelial tissue.⁶ They are usually air filled but may also contain liquid or solid material.^6,7 They vary in size, quantity, and location depending on underlying pathology.⁶ Pulmonary cysts can result from a vast array of disorders and are often found incidentally on chest images.⁶ High-resolution CT (HRCT) remains the diagnostic modality of choice for most cystic lung diseases, and in many cases tissue is needed for a definitive diagnosis.⁷ Cysts found in the lungs can be further described as blebs, bullae, or pneumatoceles (Table 2).⁷ Blebs are small cysts measuring less than 1 cm in diameter, whereas bullae are larger cysts measuring greater than 1 cm in diameter; other than size, there are few differences between blebs and bullae.⁷ Pneumatoceles are air-filled spaces in the lungs that typically are caused by trauma and are usually transient.^7,8 Given the variety of diseases and conditions that cause cystic changes in the lungs, it is useful for clinicians to understand these different entities to allow for timely diagnosis. Table 3 provides an overview of some of the more common causes of pulmonary cysts.

Table 2.

Commonly used terms for pulmonary cysts seen on radiologic imaging^a

Term	Definitiona
Cyst	Round, circumscribed space containing air, fluid, or solid material surrounded by a thin wall (< 2 mm) of fibrous or epithelial tissue
Bleb	Gas-containing space that measures ≤ 1 cm in diameter
Bulla	Gas-containing space that measures > 1 cm in diameter
Pneumatocele	Air-filled space in the lung usually resulting from trauma; tends to be transient

¹Fleischner Society: Glossary of terms for thoracic imaging. Radiology 2008 Mar;246(3):697–722.

Table 3.

Common causes of pulmonary cysts

Cause	Examples
Neoplastic	Lymphangiomyomatosis Pulmonary Langerhans cell histiocytosis Pleuropulmonary blastoma Other primary and metastatic neoplasms (especially metastatic angiosarcomas)
Smoking-related lung disease	Pulmonary Langerhans cell histiocytosis Desquamative interstitial pneumonia Respiratory bronchiolitis-associated interstitial lung disease
Infectious	Pneumocystis jiroveci pneumonia Cystic echinococcosis (pulmonary hydatid disease) Staphylococcal pneumonia Coccidioidomycosis Recurrent respiratory papillomatosis Paragonimiasis
Hereditary/congenital	Birt-Hogg-Dubé syndrome Neurofibromatosis Ehlers-Danlos syndrome Congenital airway malformation
Other interstitial lung disease	Idiopathic pulmonary fibrosis Desquamative interstitial pneumonia Hypersensitivity pneumonitis Sarcoidosis
Lymphoproliferative disease	Lymphocytic interstitial pneumonia Sjögren syndrome Amyloidosis Light-chain deposition disease

Neoplastic Causes of Pulmonary Cysts

It is uncommon for lung tumors (either primary or metastatic tumors) to produce cystic changes in the lung. Metastatic cancers produce cysts more commonly than do primary tumors, and among these, sarcomas (most notably scalp angiosarcomas) are particularly prone to induce cystic changes.⁶

Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive disease in which the lung is infiltrated with smooth-muscle cells.^6,9 These aberrant cells contain growth-activating mutations in the tuberous sclerosis genes.¹⁰ LAM is almost exclusively seen in women, with an average age at diagnosis in the mid-30s.^10,11 The disease can occur sporadically or in patients with underlying tuberous sclerosis (Figure 4). More than 30% of women with tuberous sclerosis have LAM vs only 10% to 15% of men with tuberous sclerosis.^9,11 LAM is 5 to 10 times more common in association with tuberous sclerosis than in its sporadic form.⁶ Similar to patients with other types of cystic lung diseases, patients with LAM often present with nonspecific symptoms such as cough, dyspnea, chest pain, and pneumothorax.⁶ Biopsy remains the gold standard for the diagnosis of LAM; however, HRCT features of LAM are highly characteristic, and in many cases a biopsy is not needed.⁶ Patients with LAM typically have higher serum levels of vascular endothelial growth factor D, which can be a useful marker in aiding in the diagnosis of LAM, particularly in patients who present with isolated lung cysts.⁶ In 2010, diagnostic guidelines were published by the European Respiratory Society LAM Task Force.¹² Long-term prognosis is poor given the progressive nature of lung disease in LAM.⁶ There is no cure for LAM; however, mammalian target of rapamycin kinase inhibitors such as sirolimus have been determined to be effective drugs in treating LAM because mutations in tuberous sclerosis complex genes contribute to activation of mammalian target of rapamycin kinase.^6,10 The only curative therapy appears to be lung transplant; however, recurrence rates are high, and recurrence also can occur in transplanted lungs.⁶

Figure 4.

Computed tomography scan of the lungs of a patient with tuberous sclerosis complex with lymphangiomyomatosis, demonstrating multiple lung cysts diffusely throughout the lungs.

Pulmonary Langerhans cell histiocytosis (PLCH), formerly called eosinophilic granuloma of the lung, is seen predominantly in young smokers (in approximately 90% of cases) or in patients with substantial secondhand smoke exposure.^10,13 The average age at onset is typically in the third and fourth decades of life.⁶ Langerhans cells, which are differentiated cells of the monocyte-macrophage line, help regulate bronchial mucosal immunity.¹⁰ In PLCH, there is abnormal peribronchiolar accumulation of these cells along with other immune cells and formation of granulomas.^6,10 It is thought that cigarette smoking induces gene mutations that allow unregulated growth of Langerhans cells, leading to the formation of cellular nodules.¹⁰ As the disease progresses, nodules cavitate and cause bronchial dilation that results in cystic lung changes.^6,14 Unlike many interstitial lung diseases, the lung changes of PLCH predominate in the mid and upper lung zones.¹⁰ Figure 5 shows a CT scan of PLCH.

Figure 5.

Computed tomography scan of the lungs of a patient with early-stage pulmonary Langerhans cell histiocytosis, demonstrating multiple bilateral lung cysts.

The disease course of PLCH is variable, ranging from patients who are asymptomatic to those who have a progressive course leading to respiratory failure.¹³ Diagnosis can be made clinically with radiologic evidence by HRCT; however, a definitive diagnosis may require bronchoalveolar lavage with identification of greater than 5% of Langerhans cells.⁶ Therapeutic management should begin with smoking cessation, because the disease may resolve with just this behavioral modification.⁶ Drug treatments have been disappointing, but glucocorticoids and cladribine have been used.⁶

Pleuropulmonary blastoma is a very rare and highly aggressive malignant neoplasm that occurs most commonly in children under the age of 5 years.^15–17 It arises from either the lungs or pleura and accounts for less than 1% of all pediatric primary lung neoplasms.¹⁶ Histologically, it resembles fetal tissue characterized by primitive blastema with benign epithelial elements and by malignant mesenchymal stroma with the potential for sarcomatous differentiation.¹⁵ Pleuropulmonary blastomas can be classified into 4 types. Type 1 has a purely cystic component, Type 2 has a mixed component with both solid and cystic features, and Type 3 has a purely solid component. The fourth type, Type 1r (Type 1-regressed), which was added in 2006 by the International Pleuropulmonary Blastoma Registry, has a cystic component containing spindle-shaped cells in the wall of the cyst with foci of dystrophic calcification.^17,18 Diagnosis is made by histologic evaluation of the tumor, either after excision of the mass or by fine-needle aspiration; however, this testing may not provide a conclusive diagnosis.¹⁷ Prognosis remains poor despite a multimodal approach to treatment.¹⁵ The mainstay of therapy is surgical resection of the tumor with the addition of chemotherapy and less often radiotherapy.¹⁵

Smoking-Related Causes of Pulmonary Cysts

Cigarette smoking has been linked to a variety of diffuse cystic lung diseases. As mentioned previously, PLCH is one of those diseases. Other disorders include desquamative interstitial pneumonia (DIP), respiratory bronchiolitis-associated interstitial lung disease (Figure 6), and emphysema.^10,19,20 Both DIP and respiratory bronchiolitis-associated interstitial lung disease are types of idiopathic interstitial pneumonias that fall under the larger category of interstitial lung diseases.²⁰ In DIP, histologically pigmented macrophages are dispersed throughout the alveolar spaces.²⁰ DIP occurs mostly in adults, with an average age at onset of 40 years, and occurs more frequently in males with approximately a 2:1 ratio.²⁰ The disease is almost exclusively seen in smokers (approximately 90%), with other inciting factors being occupational/environmental exposures, medications, infections, and other systemic disorders.²⁰

Figure 6.

Computed tomography scan of the lungs in a patient with respiratory bronchiolitis, demonstrating scattered bilateral areas of ground-glass opacities and lung cysts.

As in DIP, pigmented macrophages are also seen in respiratory bronchiolitis-associated interstitial lung disease; however, instead of extensive and diffuse scattering, they tend to accumulate in peribronchiolar spaces and nearby alveoli.²⁰ The average age at onset is in the fourth to fifth decades of life.²⁰ The disease often resolves with smoking cessation.²⁰

Infectious Causes of Pulmonary Cysts

Pneumocystis jiroveci pneumonia (Figure 7) almost exclusively affects severely immunocompromised persons, especially those with HIV and a CD4 count of less than 200/mm.^3,6,21 The most common features on HRCT in patients with P jiroveci pneumonia are ground-glass opacities.²¹ Cystic lung changes are seen less commonly but can be observed on HRCT scans in 10% to 30% of patients with AIDS.²¹ Cysts are typically not observed until after multiple infections and tend to occur in the lung apices.⁶ Diagnosis can be made by sputum examination or bronchoalveolar lavage; however, transbronchial biopsy may be needed for a subset of patients.⁶ The recommended first line of treatment is with trimethoprim-sulfamethoxazole regardless of severity of the disease.²² Other therapies include dapsone, primaquine, clindamycin, and pentamidine atovaquone, used alone or in combination depending on the patient’s tolerance or other medical conditions.²²

Figure 7.

Computed tomography scan of the lungs in a patient diagnosed with pneumocystis pneumonia, demonstrating bilateral pneumothorax and multiple pneumatoceles in the right lung.

Cystic echinococcosis (pulmonary hydatid disease) is a parasitic disease caused by Echinococcus granulosus.²³ The disease is endemic in most Mediterranean countries, Northern and Eastern Africa, Central Asia, South America, and Australia.²³ E granulosus most commonly affects the liver—in about two-thirds of patients—with the lungs being the second most common site of involvement—in about one-fourth of patients.²³ Pulmonary hydatid disease (Figure 8) can occur as a primary or secondary infection. Primary hydatidosis occurs by direct ingestion of eggs into the gastrointestinal tract, and larvae penetrate through the intestinal wall into the portal circulation and then proceed to the systemic circulation via the liver, eventually making their way to the lungs.²³ Secondary disease occurs by rupture of a primary cyst, thereby releasing multiple other daughter cysts into the lungs.²³ Cysts tend to be solitary and unilateral, with the right lung being most commonly affected.²³ Patients may be asymptomatic, especially when cysts are small and not compressing any adjacent structures.²³ Symptoms typically occur with large cysts (> 5 cm) or with complications such as cyst rupture or pneumothorax.²³ Patients with ruptured cysts may have peripheral blood eosinophilia and leukocytosis.²³ Pulmonary hydatid disease should be suspected in an individual with radiologically proven pulmonary cysts who is from an endemic area with exposure to sheep or dogs.²³ The disease is managed primarily by antihelminthic medications (albendazole) and/or surgery when intervention is indicated; surgery is the preferred treatment of choice for larger cysts.²³

Figure 8.

Computed tomography scan of the lungs in a patient with a diagnosis of pulmonary hydatid cyst, demonstrating a large cyst with a thick wall in the right lung.

Paragonimiasis is a parasitic infection acquired after ingestion of freshwater crabs or crayfish containing larvae of Paragonimus westermani.^10,23 Larvae migrate through the intestinal wall into the systemic circulation and then into the lungs and pleural spaces, where formation of cysts can occur.¹⁰ Cysts develop because of obstruction of a blood vessel by migrating worms, resulting in infarction.¹⁰ Diagnosis is made by identification of eggs in sputum examination or bronchoalveolar lavage and by positive serologic findings.¹⁰ Prognosis is favorable with antihelminthic treatment (praziquantel), which is effective in almost all patients.¹⁰

Other infections known to cause cystic changes in the lungs are staphylococcal pneumonia, coccidioidomycosis, and recurrent respiratory papillomatosis (a pediatric disorder caused by human papillomavirus).¹⁰

Genetic and Congenital Diseases Causing Pulmonary Cysts

Birt-Hogg-Dubé syndrome is a rare autosomal dominant multisystem disorder primarily involving the skin, kidneys, and lungs (Figure 9).^6,8 The syndrome is a result of mutations (more than 100 mutations have been identified) in the FLCN gene, which codes for the protein folliculin.²⁴ Hair follicle tumors (fibrofolliculomas), along with renal cysts or neoplasms and lung cysts, are all characteristic findings of the disorder; however, not all 3 findings may be present at the same time.^8,24 In a study by Gunji et al,²⁴ 5 of 8 patients with multiple lung cysts of unknown etiology were found to have germline mutations consistent with Birt-Hogg-Dubé syndrome despite not having any skin or renal involvement. The disease is typically seen in the third and fourth decades, with no predilection for sex.⁶ Renal findings can present as benign cysts, benign tumors, or malignant neoplasms such as renal cell carcinoma.²³ Cystic changes in the lung have been attributed to defects in the gene encoding for the tumor suppressor protein folliculin, hence the more appropriate term folliculin gene-associated syndrome.^6,24 Patients with pulmonary involvement most commonly present with spontaneous pneumothorax, although the most common presentation in all patients are papules.⁶ Diagnosis is made by identification of mutation in the FLCN gene and by clinical manifestation of skin lesions, lung cysts, and/or renal tumors.⁶ Overall the progression of lung disease in Birt-Hogg-Dubé syndrome is slow and is not well understood; however, respiratory failure does not typically occur.⁸

Figure 9.

Computed tomography scan of the lungs in a patient with Birt-Hogg-Dubé syndrome, demonstrating multiple lung cysts.

Neurofibromatosis, Ehlers-Danlos syndrome, bronchopulmonary dysplasia, and congenital airway malformations are other genetic diseases that can cause cysts in the lungs.⁶

Interstitial Lung Diseases

A few types of interstitial lung diseases may present with cystic changes in the lungs. Among these are idiopathic pulmonary fibrosis, hypersensitivity pneumonitis (HP), and sarcoidosis.¹⁰ Idiopathic pulmonary fibrosis is predominantly associated with fibrosis and other fibrotic features (eg, reticulation, honeycombing, traction bronchiectasis) rather than cysts; however, distribution of cysts can be helpful in differentiating among the types of interstitial lung diseases.¹⁰

HP, or extrinsic allergic alveolitis, is an immune-mediated response to repeated exposures of the lung parenchyma to inhaled antigens, resulting in inflammation.²⁵ HP can be categorized into acute, subacute, and chronic types, with chronic HP (Figure 10) identified as the stage with evidence of fibrosis seen on either radiologic imaging (HRCT) or histologic findings.²⁵ Acute and subacute HP tend to resolve after the offending agent has been removed, whereas chronic HP is a slowly progressive disease, often with irreversible damage.²⁵ Cysts are rarely seen in acute HP but can be seen in subacute HP and chronic HP, with the latter being much more common.¹⁰ The cysts are presumed to result from damage to bronchioles and tend to occur in areas of ground-glass attenuations.^10,25 Diagnosis can be made with a history of environmental or occupational exposure to a possible inciting agent, clinical manifestations, HRCT findings suggestive of HP, and, if needed, lung biopsy.²⁵ Management involves identifying and removing the offending agent and the use of corticosteroids.²⁵ Resolution can be seen in acute and subacute HP with removal of the offending agent and/or use of corticosteroids; however, with chronic HP there usually has already been irreversible damage.²⁵

Figure 10.

Computed tomography scan of the lungs in a patient diagnosed with chronic hypersensitivity pneumonitis, demonstrating peripheral cysts in the left lung.

Sarcoidosis is a noncaseating, granulomatous disease that mainly involves the lungs (Figure 11) but can affect many other organ systems such as the heart, skin, eyes, liver, central nervous system, and kidneys.²⁶ The disease can affect individuals of all ages and ethnicities but more commonly occurs in women younger than age 50 years.²⁷ Incidence varies across the world; however, in the US, incidence is about 3 times higher in African Americans compared with whites.²⁷ Noncaseating granulomas seen on histologic findings are the hallmark of sarcoidosis.²⁵ On HRCT, perihilar lymphadenopathy and nodules are more commonly seen than cysts.²⁵ Formation of cysts occur because of obstruction of lobar or segmental bronchi by fibrosis or accumulation of granulomas.²⁵ Cysts are occasionally seen in the perihilar or subpleural regions.^10,25 Treatment is reserved for symptomatic patients with worsening organ involvement.²⁸ The mainstay of therapy is corticosteroids; however, steroid-sparing agents such as methotrexate, azathioprine, leflunomide, and mycophenolate mofetil have also been used.^25,28 Lung transplant can be an option for those with end-stage lung disease in whom other medical therapies have failed; however, posttransplant prognosis is unclear in these patients because of the multisystem involvement of sarcoidosis.²⁸

Figure 11.

Computed tomography scan of the lungs in a patient with sarcoidosis, demonstrating patchy bilateral areas of consolidation, scattered micronodular changes, and lung cysts.

Lymphoproliferative Causes of Pulmonary Cysts

Lymphocytic interstitial pneumonia (LIP) is a benign lymphoproliferative disorder characterized by diffuse lymphocytic infiltration of the lung parenchyma (Figure 12).⁸ This type of pneumonia is most common in women in their 30s and 40s.⁶ It can occur as a form of idiopathic interstitial pneumonia or in association with other disorders such as Sjögren syndrome, rheumatoid arthritis, systemic lupus erythematosus, HIV infection, Hashimoto thyroiditis, and common variable immune deficiency.^6,8 The presence of polyclonal lymphocytes is a key factor in differentiating LIP from lymphomas, in which monoclonal lymphocytes are seen.⁸ LIP is a progression from hyperplasia of bronchus-associated lymphoid tissue (follicular bronchiolitis) to cellular expansion of the interstitium, which can result in postobstructive bronchial ectasia; vascular obstruction; and/or bronchiolar stenosis, occlusion, or compression.⁸ Any of these entities can lead to the development of pulmonary cysts.⁸ Pulmonary cysts develop in approximately 60% to 80% of patients with LIP.⁶ Management and prognosis is dependent on the underlying disease. Corticosteroids are commonly used; however, the disease does not always respond to treatment and can progress to respiratory failure.⁶

Figure 12.

Computed tomography scan of the lungs showing thin-walled cysts in a patient with lymphocytic interstitial pneumonia.

Sjögren syndrome is an autoimmune disease characterized by lymphocytic infiltration of exocrine glands.²⁹ The disease predominantly affects middle-aged women.²⁹ Depending on the presence or absence of other autoimmune disorders such as systemic lupus erythematosus, rheumatoid arthritis, or systemic sclerosis, the syndrome can be further categorized as primary (occurring alone) or secondary Sjögren syndrome (occurring with other diseases).³⁰ Systemic manifestations beyond exocrine glands can also be observed with involvement of the lungs, liver, blood vessels (vasculitis), kidneys, and central nervous system.²⁹ Sjögren syndrome has protean manifestations in the lungs, ranging from airway abnormalities to LIP and interstitial lung disease.²⁹ Lung cysts can develop as a result of interstitial lung disease or LIP.²⁹ Pulmonary involvement occurs in less than 20% of patients and indicates increased mortality.²⁹

Amyloidosis encompasses a group of diseases characterized by an abnormal deposition of fibrillary proteins.^6,8 It can occur as a systemic disease or be localized to a single organ such as the lungs (Figure 13).⁸ Although rare, amyloidosis with pulmonary involvement may present with cystic changes in the lungs.⁶ Cyst formation is thought to be caused by one or more of the following mechanisms: Narrowing of the airways as a result of infiltration of amyloid and inflammatory cells causing alveolar destruction, amyloid deposition causing increased fragility of alveolar structures, or amyloid deposition in the vasculature resulting in ischemia.⁶ Tissue biopsy is required for diagnosis, with identification of amyloid fibrillary tangles that demonstrate green birefringence and stain positive for Congo red.⁶ Patients with only pulmonary amyloidosis have a good prognosis, whereas those with amyloid-associated systemic disease have a much worse prognosis.⁶

Figure 13.

Computed tomography scan of the lungs in a patient with a diagnosis of pulmonary amyloidosis, demonstrating multiple bilateral lung cysts.

Light-chain deposition disease (LCDD) is a multisystem disease characterized by the accumulation of monoclonal immunoglobulin light chains.⁶ This disease is most commonly associated with an underlying plasma cell dyscrasia, but LCDD can be idiopathic or associated with autoimmune diseases.⁶ The kidneys are almost always involved, with the next most frequently involved organs being the heart and liver.^14,31 Pulmonary involvement occurs rarely in LCDD, but when present the most common findings are lung cysts (Figure 14), nodules, and bronchiectasis.^6,32 When LCDD is isolated to the lungs, this form of the disease is known as primary cystic lung LCDD.³³ Cystic lung LCDD was first described in 2006 and differs in various ways from the systemic form of the disease.³³ It has a predilection for young women in their 30s.³³ The mechanism of cyst formation in LCDD was explored by Colombat et al,³¹ wherein there was seen degradation of pulmonary elastin from metalloproteinases. Cystic lung LCDD is a severe disease that usually progresses to end-stage respiratory failure.^31,33 There is also an association with lymphoproliferative disorders such as lymphoplasmacytic lymphoma, mucosa-associated lymphoid tissue lymphoma, chronic lymphocytic leukemia, and gammopathy of undetermined significance.³²

Figure 14.

Computed tomography scan of the lungs in a patient with a diagnosis of light-chain deposition disease, demonstrating multiple lung cysts predominantly in the right lung.

Diagnosis of LCDD can be made histologically via biopsy of the affected organ.³³ Bronchial biopsy has also been shown to aid in diagnosis if the lung is suspected to be involved.³¹ Demonstration of the presence of fibrils that do not stain Congo red under polarized light supports the diagnosis of LCDD; however, analysis of the tissue sample by immunofluorescence and microscopy is ultimately needed to confirm the diagnosis.^31,33

There is no definite treatment of LCDD; however, lung transplant may be an option for those with advanced cystic lung LCDD, and a blood stem cell transplant may be a treatment option for patients with monoclonal disease.³³ In cases in which there is an associated lymphoproliferative disorder, other therapies may be offered such as chemotherapy and blood stem cell transplant.³² Le Borgne et al³² described a patient who was found to have cystic lung LCDD and lymphoma who was treated with chemotherapy and autologous peripheral blood stem cell transplant. The patient did not undergo lung transplant given the associated lymphoma; however, respiratory stability was achieved with the aforementioned therapy.

Integument

The skin and subcutaneous tissue, composing the integument, should be regarded as part of the body rather than as an independent organ. The skin possesses the closest relations with the general economy …

— Louis A Duhring, MD, 1845–1913, American physician and professor of dermatology