(Radiographics. 1999;19:205-233.)
© RSNA, 1999
Image Interpretation Session: 1998
The Radiological Society of North America 84th Scientific Assembly and Annual Meeting
James G. Smirniotopoulos, MD1,2,
Gael J. Lonergan, Lt Col, USAF, MC1,2,
Robert M. Abbott, Maj, USAF, MC1,3,
Peter L. Choyke, MD1,4,
Julianna M. Czum, MD1,
Neal C. Dalrymple, Maj, USAF, MC3,
Daniel DoDai, MD2,1,6,
David S. Feigin, COL, MC, USA1,
Vincent B. Ho, MD1,
John R. Leyendecker, Maj, USAF, MC3,5 and
Miguel J. Rovira, LTC, USA, MC1,7
1 Departments of Radiology, Uniformed Services University of the Health Sciences, Bethesda, Md (J.G.S., G.L., R.M.A., P.L.C., J.M.C., D.D., D.S.F., V.B.H., M.J.R.)
2 Armed Forces Institute of Pathology, Washington, DC (J.G.S., G.L.)
3 Wilford Hall Air Force Medical Center, San Antonio, Tex (R.M.A., N.D., J.R.L.)
4 National Institutes of Health, Bethesda, Md (P.L.C.)
5 Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, Md (J.R.C.)
6 Tripler Army Medical Center, Honolulu, Hawaii (D.D.)
7 Madigan Army Medical Center, Tacoma, Wash (M.J.R.).
Index Terms: Arteriovenous malformations, pulmonary, 60.1494 • Emphysema, pulmonary, 60.7532 • Histiocytosis, 411.661, 60.66 • Melanoma, 76.332 • Neurofibromatosis, 83.18 • Sarcoidosis, 60.223, 752.22 • Sclerosis, tuberous, 161.1832 • Temporal bone, neoplasms, 2136.3631 • Thymus, cysts, 275.373 • von Hippel–Landau disease, 1531.699, 770.699, 81.699, 847.699
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CASE 1
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HISTORY
A 31-year-old man presented with bilateral scrotal masses. Ultrasonography (US) of the left and right scrotum was performed and demonstrated bilateral extratesticular masses (Fig 1).
Because the patient was known to be at risk for von Hippel–Lindau (VHL) disease, computed tomography (CT) and magnetic resonance (MR) imaging were performed as part of a periodic surveillance examination to monitor the development and progression of complications of this disease. Contrast material–enhanced CT of the patient's abdomen revealed multiple abnormalities, including cystic masses of the kidneys and pancreas, indicative of a systemic disease (Fig 2). MR imaging of the head revealed a cystic mass in the left cerebellar hemisphere (Fig 3). The interpreting radiologist suspected previous resection of bilateral adrenal pheochromocytomas and an inflammatory (vs neoplastic) origin of the scrotal masses.
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Figure 2a. Case 1. Axial contrast-enhanced CT scans through the pancreas (a at a higher level than b) demonstrate multiple abnormalities, including heterogeneous cystic renal masses, extensive replacement of the pancreas by largely cystic heterogeneous masses, and surgical clips in the region of both adrenal glands.
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Figure 2b. Case 1. Axial contrast-enhanced CT scans through the pancreas (a at a higher level than b) demonstrate multiple abnormalities, including heterogeneous cystic renal masses, extensive replacement of the pancreas by largely cystic heterogeneous masses, and surgical clips in the region of both adrenal glands.
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DIAGNOSIS: Bilateral epididymal cystadenomas, pancreatic and renal cysts, and cerebellar hemangioblastoma in the setting of VHL disease.
DISCUSSION
VHL disease was originally described as the familial association of multiple vascular "angiomas" of the retina (von Hippel disease) with hemangioblastoma (the Lindau tumor). However, it was soon recognized that the affected patients had a more complex, systemic disease, with cysts and both benign and malignant neoplasms affecting the solid abdominal organs (kidneys and pancreas). The skin, however, is not affected (unlike the manifestations of classic phakomatoses). VHL disease has an autosomal dominant inheritance pattern, without racial or sexual predilection, and the responsible gene has been identified on chromosome 3p. The prevalence of VHL disease in the United States is estimated at about one in 35,000 to one in 50,000 people.
The study group at the National Institutes of Health has suggested subclassifying VHL disease into three subtypes: type I, type IIA, and type IIB. In type I VHL disease (the most common), patients have the classic features of renal and pancreatic cysts, a high risk for developing renal cell carcinoma, and no pheochromocytomas. In type IIA VHL disease, patients have pheochromocytomas and pancreatic islet cell tumors (typically without cysts). In type IIB VHL disease, patients have pheochromocytomas and both renal and pancreatic disease. In this case, the patient had evidence of previous adrenal surgery for pheochromocytoma and pancreatic and renal cysts; thus, his disease was classified as type IIB VHL disease.
More than half of the patients with VHL disease will develop or present with retinal angiomas. These tumors are actually hemangioblastomas of the retina and cause retinal hemorrhage and detachment. Two-thirds or more patients will have hemangioblastomas of the brain; these tumors are usually infratentorial, with the cerebellum being the most common site. In addition, patients with VHL disease are prone to develop multiple hemangioblastomas that may occur simultaneously or may appear as metachronous (asynchronous) lesions. Although hemangioblastoma is a benign nonglial neoplasm, it is hypervascular and may recur if incompletely resected.
As this case illustrates, patients with VHL disease may also develop benign cystadenomas in the epididymis (Figs 4, 5). Epididymal cystadenomas are uncommon tumors that, even as sporadic lesions, are believed to arise from a somatic mutation in the same gene associated with VHL disease on chromosome 3p. The presence of bilateral epididymal tumors, however, suggests a germline systemic mutation, rather than a local somatic mutation. Thus, a patient with such tumors most likely has VHL and should be evaluated for other manifestations.
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Figure 5. Case 1. High-power photomicrograph (original magnification, x40; hematoxylin-eosin [H-E] stain) of a section of epididymis shows papillary structures, characteristic of cystadenoma.
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The presence of multiple lesions should always suggest a systemic disease. Systemic diseases may be congenital (maldevelopmental and genetic), inflammatory (infectious, autoimmune), toxic, metabolic, and neoplastic (metastasis). Hematogenous dissemination of neoplasms and infection may create multiple and often bilateral lesions, but they are usually located in asymmetric and somewhat random patterns. However, toxic, metabolic, and genetic lesions may have bilateral and strikingly symmetric anatomic distributions.
In the differential diagnosis of this case, the bilateral masses of the scrotal sac could have been caused by infection. However, the location of the masses with anatomic symmetry within the epididymis (Fig 4) suggests consideration of a syndrome. In addition, the morphology of the masses as heterogeneously solid and cystic also suggests the specific diagnosis of a cystadenoma (Fig 1). These two clues fit together well if the patient has VHL disease. Of course, in this case, the additional findings of renal and pancreatic lesions provided further evidence of a systemic disease.
SUGGESTED READINGS
- Binkovitz LA, Johnson CD, Stephens DH. Islet cell tumors in von Hippel–Lindau disease: increased prevalence and relationship to the multiple endocrine neoplasias. AJR 1990; 155:501–505.
- Choyke PL, Glenn GM, Walther MM, et al. The natural history of renal lesions in von Hippel–Lindau disease: a serial CT study in 28 patients. AJR 1992; 159:1229–1234.
- Choyke PL, Glenn GM, Walther MM, Patronas NJ, Linehan WM, Zbar B. von Hippel–Lindau disease: genetic, clinical, and imaging features. Radiology 1995; 194:629–642.
- Ho VB, Smirniotopoulos JG, Murphy FM, Rushing EJ. Radiologic-pathologic correlation: hemangioblastoma. AJNR 1992; 13:1343–1352.
- Neumann H. Basic criteria for clinical diagnosis and genetic counseling in von Hippel–Lindau syndrome. Vasa 1987; 16:220–226.
- Tibbs RE Jr, Bowles AP Jr, Raila FA, Fratkin JD, Hutchins JB. Should endolymphatic sac tumors be considered part of the von Hippel–Lindau complex? Neurosurgery 1997; 40:848–855.
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CASE 2
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HISTORY
A 38-year-old white man presented with a 6-week history of low-grade, constant abdominal pain. One month earlier, the patient had undergone removal of a scalp lesion that had been diagnosed as an irritated compound nevus. He denied other gastrointestinal complaints, and physical examination revealed only vague upper abdominal tenderness. Results of the laboratory studies revealed a mildly elevated level of lactate dehydrogenase, but all other laboratory values were within normal limits. Initially, he underwent contrast-enhanced CT of the abdomen and pelvis, which demonstrated some mass effect on the falciform ligament from the left lobe of the liver (Fig 6).
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Figure 6. Case 2. Contrast-enhanced CT scan of the abdomen obtained shortly after skin biopsy reveals a slight mass effect on the falciform ligament from the left hepatic lobe; however, no discrete masses are seen.
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Routine reevaluation of the tissue obtained in the skin biopsy revealed malignant melanoma. For further evaluation, MR imaging was performed and demonstrated a large lesion in the left hepatic lobe (Fig 7) and a suspicious abnormality in the spine. Follow-up MR images obtained 2 months later revealed many small lesions throughout the liver (Fig 8), as well as in the vertebral bodies, and periportal and periceliac adenopathy.
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Figure 7a. Case 2. (a) Unenhanced T1-weighted image demonstrates an ill-defined, heterogeneous 7 x 4 cm mass in the left hepatic lobe with high signal intensity relative to that of liver parenchyma. (b, c) On proton-density–weighted (b) and T2-weighted (c) fast spin-echo images, the lesion remains high in signal intensity, with slight diminution in intensity with the more heavily T2-weighted pulse sequence (c).
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Figure 7b. Case 2. (a) Unenhanced T1-weighted image demonstrates an ill-defined, heterogeneous 7 x 4 cm mass in the left hepatic lobe with high signal intensity relative to that of liver parenchyma. (b, c) On proton-density–weighted (b) and T2-weighted (c) fast spin-echo images, the lesion remains high in signal intensity, with slight diminution in intensity with the more heavily T2-weighted pulse sequence (c).
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Figure 7c. Case 2. (a) Unenhanced T1-weighted image demonstrates an ill-defined, heterogeneous 7 x 4 cm mass in the left hepatic lobe with high signal intensity relative to that of liver parenchyma. (b, c) On proton-density–weighted (b) and T2-weighted (c) fast spin-echo images, the lesion remains high in signal intensity, with slight diminution in intensity with the more heavily T2-weighted pulse sequence (c).
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Figure 8a. Case 2. Follow-up unenhanced fat-suppressed T1-weighted MR images show many small (<1-cm), diffuse lesions throughout the liver. On the image obtained at a slightly lower level (b), these lesions are more conspicuous, and a lesion is visible in the vertebral body.
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Figure 8b. Case 2. Follow-up unenhanced fat-suppressed T1-weighted MR images show many small (<1-cm), diffuse lesions throughout the liver. On the image obtained at a slightly lower level (b), these lesions are more conspicuous, and a lesion is visible in the vertebral body.
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DIAGNOSIS: Malignant melanoma metastatic to the liver and spine.
DISCUSSION
Worldwide incidence of melanoma has been rising over the past several decades, with the estimated annual incidence increasing in the United States at approximately 3.9% per year. Although melanoma occurs in patients of all ages, the peak prevalence is in those 40–60 years of age. Most often, melanoma develops in the skin, but it is also seen in mucous membranes, leptomeninges, and the eye. Melanoma frequently metastasizes widely. Regional lymph nodes, the liver, the lungs, and the brain are likely to be involved.
Two distinct features of melanoma that assist in the clinical differentiation of these lesions from benign nevi are color and border characteristics. Specifically, nevi are usually shades of tan to dark brown, with regular, well-circumscribed borders. Melanomas, on the other hand, have areas of red, white, or blue in addition to brown and black. The borders of melanomas are irregular, with notching and striking protrusions. With identification of these features, the accuracy of clinical diagnosis approaches 90%.
Most melanomas arise de novo, but about 20% are associated with a preexisting benign nevus. Precursor lesions of malignant melanoma include dysplastic moles, atypical melanocytic hyperplasia, and some congenital melanocytic nevi. Other risk factors include xeroderma pigmentosum, melanoma in a first-degree relative, sun-sensitive phenotype, and excessive sun exposure.
The staging of malignant melanoma, according to the American Joint Commission on Cancer, depends on microstaging and the presence or absence of both regional and distant metastases. Microstaging is performed on punch or excisional biopsy specimens of the primary lesion. Node dissection and sentinel node biopsy are then considered. Sentinel node biopsy is performed either intraoperatively with an intradermal injection of dye or preoperatively with lymphoscintigraphy. Fine-needle aspiration biopsy may be performed on palpable soft-tissue and nodal masses.
Evaluation for the possibility of hepatic metastases, may be performed with an inexpensive imaging study such as US. The practice of routine imaging with more sophisticated and expensive modalities is more likely to uncover benign (false-positive) disease in the low-risk, asymptomatic patient (stage I and II disease) and is therefore discouraged. In that patient population, however, baseline chest radiographs and tests for lactate dehydrogenase levels are relatively inexpensive, and the results may be compared with those of future studies if and when symptoms arise. Lactate dehydrogenase levels, for example, may provide a sensitive indicator for screening for hepatic metastases or reflect the presence of recurrent tumor burden.
In patients with local or regional metastases (stage III disease), the value of CT and MR imaging for detecting clinically occult disease has not been demonstrated. Instead, the imaging evaluation is tailored to investigate symptoms or physical findings for these patients. Thus, routine imaging of the head, chest, abdomen, and pelvis is performed in patients with stage IV disease, but otherwise it has a relatively limited role.
In melanoma, US and CT findings are varied and nonspecific. MR imaging is more sensitive and has greater specificity for detection and identification of melanoma metastases in the liver. The signal intensity of these lesions varies according to the histopathologic components of the tumor. Most commonly, the lesions are hypo- or isointense (relative to uninvolved liver) on T1-weighted, T2-weighted, and short-inversion-time inversion recovery (STIR) images. This pattern is not specific. A less frequent, but more distinctive pattern of hyperintensity, is T1-weighted images and hypointensity or isointensity on T2-weighted and STIR images. In a few cases, a mixed pattern (ie, a spectrum of findings) will occur in different lesions in the same patient. The type of pattern displayed does not correlate with lesion size. In this case, high signal intensity of hepatic lesions on T1-weighted images suggested the presence of melanin, related to the T1 shortening effects of paramagnetic metals (eg, iron and copper) bound to melanin and therefore the overall tumor melanin content. The greatest conspicuity (visual contrast-to-noise ratio) of melanoma lesions is seen on STIR or conventional fat-suppressed T1-weighted spin-echo images, as in this case. Use of gadolinium-based contrast material does not increase the number of lesions detected nor their conspicuity. In fact, tumor enhancement can obscure hypointense lesions.
The differential diagnosis of high-signal-intensity hepatic melanoma metastases on T1-weighted MR images includes both truly hyperintense and relatively hyperintense lesions. Truly hyperintense, endogenous substances include fat (such as in rounded focal fat deposits, which can mimic metastases but lose signal intensity with fat-suppressed sequences), high protein content (as in some other malignant liver lesions), hemorrhage (methemoglobin) as occurs in tumors or after biopsy, and melanoma metastases. On unenhanced fat-suppressed T1-weighted images (Fig 8), melanoma metastases and hemorrhagic lesions remain bright, allowing differentiation from rounded fatty deposits. Melanoma metastases can be differentiated from hemorrhage based on the knowledge of the underlying primary tumor in melanoma versus the central location of high signal intensity and lack of enhancement of a purely hemorrhagic lesion on T1-weighted images. Exogenous substances that are truly hyperintense on T1-weighted images include paramagnetic contrast agents and iodized oil, but knowledge that these substances were administered allows them to be excluded from the differential diagnosis. Normally, on heavily T1-weighted images, the liver should be hyperintense relative to the spleen. However, in conditions such as iron overload, the spleen and liver may be equally hypointense; thus, hepatocellular carcinoma, for example, may appear relatively hyperintense. Exogenous substances with similar effects include supermagnetic iron particles (ferrite) taken up by the reticuloendothelial system. Ghost artifact can also displace signal in the phase-encoding direction, which simulates a hyperintense lesion but is usually readily recognizable.
Use of T2-weighted pulse sequences may help in further differentiating benign from malignant lesions. For example, the appearance of a T1-hyperintense lesion with a ring that is hypointense compared with the center of the lesion on T2-weighted images indicates a hematoma. This degree of organization occurs only rarely in tumor hemorrhage.
Management of melanoma involves many approaches, with surgical excision being the mainstay of treatment of the primary tumor as well as local recurrence and for the palliation of symptomatic distant metastases. Radiation therapy is used for both local and regional control and palliation of symptomatic spread. Other treatment options include systemic single-agent and combination chemotherapy for metastatic melanoma, isolated hyperthermia chemotherapy perfusion for limb melanoma (such as in transit metastases, which are those trapped in lymphatics en route to regional nodes), and, potentially, immunotherapy (interferon-a adjuvant therapy for positive regional lymph nodes).
Surveillance of patients at regular intervals after stage-appropriate treatment is performed to detect treatable recurrences and second primary melanomas, as well as to monitor the success of therapy. The frequency and impact of surveillance depend on disease stage. What is needed in the surveillance visit is debatable, including the role of imaging.
The most important environmental risk factor for development of melanoma is sun exposure. Prevention efforts target public health education and the public's awareness of sun exposure risks (such as avoidance of sunburn in early childhood) and of the signs (change in size, shape, and color of a preexisting nevus) and symptoms (bleeding or pruritus) of melanoma. Ultimately, such efforts should reduce both prevalence and mortality.
SUGGESTED READINGS
- Cotran RS, Kumar V, Collins T. Robbin's pathologic basis of disease. 6th ed. Philadelphia, Pa: Saunders, 1998.
- Enochs WS, Petherick P, Bogdanova A, Mohr U, Weissleder R. Paramagnetic metal scavenging by melanin: MR imaging. Radiology 1997; 204: 417–423.
- Furuta M, Suto H, Nakamoto S, Suzuki R, Hirai Y, Asanuma K. MRI of malignant melanoma of liver. Radiat Med 1995; 13:143–145.
- Heasley DD, Toda S, Mihm MC Jr. Pathology of malignant melanoma. Surg Clin North Am 1996; 76: 1223–1256.
- Kelekis NL, Semelka RC, Woosley, JT. Malignant lesions of the liver with high signal on T1-weighted MR images. JMRI 1996; 6:291–294.
- Lee MJ, Hahn PF, Saini S, Mueller PR. Differential diagnosis of hyperintense liver lesions on T1-weighted MR images. AJR 1992; 159:1017–1020.
- Premkumar A, Marincola F, Taubenberger J, Chow C, Venzon D, Schwartzentruber D. Metastatic melanoma: correlation of MRI characteristics and histopathology. JMRI 1996; 1:190–194.
- Premkumar A, Sanders L, Marincola F, Feuerstein I, Concepcion R, Scwartzentruber D. Visceral metastases from melanoma: findings on MR imaging. AJR 1992; 158:293–298.
- Ries LAG, Miller BA, Hankey BF, et al. SEER cancer statistics review, 1973–1991: tables and graphs. NIH publication no. 94-2789. Bethesda, Md: National Cancer Institute, 1994.
- Ross MI. Staging evaluation and surveillance for melanoma patients in a fiscally restrictive medical environment: a commentary. Surg Clin North Am 1996; 76:1423–1432.
- Semelka RC, Bagley AS, Brown ED, Kroeker MA. Malignant lesions of the liver identified on T1- but not T2-weighted MR images at 1.5 T. JMRI 1994; 4:315–318.
- Soyer P, Bluemke DA, Rymer R. MR imaging of the liver: technique. Magn Reson Clin North Am 1997; 5:205–221.
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CASE 3
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HISTORY
A 3-month-old baby boy with increasing tachypnea was admitted to the hospital. Chest radiographs were obtained on days 1 (Fig 9), 19 (Fig 10), and 23 (Fig 11) of his stay and revealed substantial, progressive cystic disease in both lungs and multiple, lucent bone lesions, including those in the left clavicle.
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Figure 9a. Case 3. Frontal (a) and lateral (b) chest radiographs of a 3-month-old boy obtained on the day of admission show ill-defined nodular opacities in both lungs and early cyst formation in the right lung. Two expansile, lytic lesions of the left clavicle are also seen on the frontal radiograph (arrows).
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Figure 9b. Case 3. Frontal (a) and lateral (b) chest radiographs of a 3-month-old boy obtained on the day of admission show ill-defined nodular opacities in both lungs and early cyst formation in the right lung. Two expansile, lytic lesions of the left clavicle are also seen on the frontal radiograph (arrows).
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Figure 10. Figures 10, 11. Case 3. (10) Lateral chest radiograph of the same infant obtained on day 19 shows substantial cystic disease throughout both lungs. (11) Frontal chest radiograph of the same infant obtained on day 23 shows a large right pneumothorax. Expansile, lytic lesions in the middle and distal third of the left clavicle are well seen.
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Figure 11. Figures 10, 11. Case 3. (10) Lateral chest radiograph of the same infant obtained on day 19 shows substantial cystic disease throughout both lungs. (11) Frontal chest radiograph of the same infant obtained on day 23 shows a large right pneumothorax. Expansile, lytic lesions in the middle and distal third of the left clavicle are well seen.
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DIAGNOSIS: Langerhans cell histiocytosis (LCH) with pulmonary and bone involvement.
DISCUSSION
LCH, sometimes referred to as histiocytosis X, is a disease of abnormal clonal proliferation of a unique type of cell in the monocyte-macrophage cell line known as the Langerhans cell. The cell is named after the medical student Paul Langerhans, who was the first scientist to describe it (in 1868). Cases of the disease were described as early as the late 1800s and ranged from solitary bone involvement to multiple lesions of bone, liver, spleen, lung, and renal pelves. These original cases, and their considerable variation in manifestations and degree of involvement, reflect the wide variability of the disease process referred to today as LCH. LCH may infiltrate many tissues, including bone, bone marrow, lung (Fig 12a), liver, spleen, brain, and kidney. Patients with solitary or limited foci of disease tend to do quite well, whereas those patients with multiorgan involvement, especially of the marrow, liver, and spleen, tend to fare much worse and may succumb to their disease.
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Figure 12a. Case 3. (a) Axial CT scan of a 16-year-old patient with LCH shows multiple cysts, some small and thick walled and others much larger and thin walled. (b) Low-power photomicrograph (original magnification, x30; H-E stain) of the patient's lung biopsy specimen shows two cysts (*), the walls of which are lined with histiocytic cellular infiltrate.
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Figure 12b. Case 3. (a) Axial CT scan of a 16-year-old patient with LCH shows multiple cysts, some small and thick walled and others much larger and thin walled. (b) Low-power photomicrograph (original magnification, x30; H-E stain) of the patient's lung biopsy specimen shows two cysts (*), the walls of which are lined with histiocytic cellular infiltrate.
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Traditionally, LCH has been divided into three forms, based on the organs involved, age of onset, and clinical course: localized, chronic disseminated, and fulminant disseminated. Localized LCH is the mildest and most common form (70%–75% of all cases) and involves either bone or lung. This limited form may be referred to as eosinophilic granuloma. The term eosinophilic granuloma derives from the considerable number of eosinophils typically seen in the bone lesions, although Langerhans cells are the dominant cellular constituent. Eosinophilic granuloma is usually monostotic when it occurs in bone, manifests in patients 5–15 years of age, and is associated with minimal morbidity. Children with localized LCH tend to have bone involvement, whereas adults have a greater propensity for lung involvement, with or without bone disease.
There are two forms of disseminated LCH: chronic and fulminant. The chronic form, also known as Hand-Schüller-Christian disease, represents about 20% of LCH cases and typically involves bone, liver, spleen, lymph nodes, and skin. Patients usually present before 5 years of age. The classic triad of diabetes insipidus (from basilar skull disease or direct infiltration of the posterior pituitary gland), exophthalmos (from mass effect of orbital bone disease), and destructive bone lesions (often of the calvaria) is seen in 10%–15% of cases. Hand-Schuller-Christian disease is fatal in approximately 15% of patients. In the fulminant form, sometimes referred to as Letterer-Siwe disease and constituting 10% of LCH cases, there is disseminated involvement of many tissues, especially liver, spleen, bone marrow, lymph nodes, and skin. Bone involvement is less common, however. This form of LCH usually occurs in children younger than 2 years old, is rapidly progressive, and usually fatal.
The histologic appearance of LCH lesions is characterized by tissue infiltration with Langerhans cells, with a mixture of mononuclear and inflammatory cells, especially eosinophils (Fig 12b). The appearance of these abnormal aggregates varies with the tissue in which they occur, as well as with the activity of the infiltrate. As the infiltrates become less active, they leave behind fibrous connective tissue and other forms of scar.
When it occurs in the skeleton, LCH has a predilection for flat bones (skull, mandible, ribs, and pelvis) and vertebral bodies (but only rarely the posterior elements). LCH involvement in long bones is most often seen in the femur, humerus, and tibia and is usually diaphyseal (58% of cases), metaphyseal (28%), metadiaphyseal (12%), or, rarely (2%), epiphyseal. Bone lesions vary widely in size, ranging from 1 to 15 cm in diameter; they are often accompanied by a tender soft-tissue mass (which may be palpable or, in the case of a rib lesion, may appear as a pleural mass). On radiographs, bone lesions of LCH usually appear lytic and may assume a geographic, permeative, or moth-eaten configuration. The borders may be well or poorly defined. In a child, such multiple, lucent lesions need to be distinguished from those that represent metastases from neuroblastoma, leukemia, or lymphoma. In the long bones, endosteal scalloping and medullary expansion are typical. Periosteal reaction is common. In the skull, the edges of the lesion may assume a beveled appearance because of asymmetric destruction of the inner and outer tables of the skull. Remnants of bone, called a "button" sequestrum, may be found within a lytic focus. In the mandible, alveolar bone may be destroyed, giving the teeth a floating appearance. In the spine, vertebral body involvement usually results in collapse, sometimes to a wafer-thin vertebra plana. As the activity of the lesion begins to wane, periostitis disappears, the margins become well defined, and reactive sclerosis may develop.
The lung is the second most common site of LCH (Figs 9–12). Pulmonary LCH is characterized by predominantly peribronchial granulomas, which appear as micronodules (1–10 mm in diameter) at CT. These lesions may cavitate, and both thick- and thin-walled cysts may be found in the lung (Fig 12). Such cysts may appear similar to pneumatoceles (caused by infection or aspiration of hydrocarbons) or to the hamartomas associated with tuberous sclerosis. In adult patients followed up over time, pulmonary LCH appears to progress from nodules to cavitary nodules, to thick-walled cysts, and then to thin-walled larger cysts. This progression is believed to reflect progressive enlargement and air trapping of the original cavitary nodules of pulmonary LCH. Some investigators theorize that these cysts develop from a ball-valve effect on the bronchus caused by granuloma formation. Depending on the severity of lung disease, progression to air-flow obstruction, impaired diffusing capacity, respiratory failure, and pulmonary arterial hypertension may result. Fortunately, pulmonary involvement does not appear to convey a poor prognosis, at least in children. Adults with pulmonary LCH almost always have a history of past or present cigarette smoking. It is theorized that components of cigarette smoke are antigenic, initiating Langerhans cell response and proliferation.
In the liver, LCH assumes a nodular form, appearing echogenic at US and usually hypoattenuated relative to adjacent parenchyma at contrast-enhanced CT. It may also result in periportal fibrosis. In the kidney, LCH may cause hydronephrosis from pelvic mass effect. The spleen may be enlarged.
Treatment of LCH varies with the severity of the disease. Limited bone disease may simply be observed after the diagnosis is established (usually with biopsy). Various chemotherapeutic agents may be used, with the amount and duration of therapy depending on severity of organ involvement. Regimens including steroids, methotrexate, and other agents have been found to be variably effective. Radiation therapy may be used to treat painful bone lesions or those at risk for pathologic fracture.
SUGGESTED READINGS
- Brauner MW, Grenier P, Tijani K, Battesti JP, Valeyre D. Pulmonary Langerhans cell histiocytosis: evolution of lesions on CT scans. Radiology 1997; 204:497–502.
- David R, Oria RA, Kumar R, et al. Radiologic features of eosinophilic granuloma of bone. AJR 1989; 153:1021–1026.
- Meyer JS, Harty MP, Mahboubi S, et al. Langerhans cell histiocytosis: presentation and evolution of radiologic findings with clinical correlation. RadioGraphics 1995; 15:1135–1146.
- Moore ADA, Godwin JD, Müller NL, et al. Pulmonary histiocytosis X: comparison of radiographic and CT findings. Radiology 1989; 172:249–254.
- Siegelman SS. Taking the X out of histiocytosis X. Radiology 1997; 204:322–324.
- Stull MA, Kransdorf MJ, Devaney KO. Langerhans cell histiocytosis of bone. RadioGraphics 1992; 12:801–823.
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CASE 4
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HISTORY
A 43-year-old man with an anterior neck mass that had been present for years presented with palpable lymph nodes on the right side. Contrast-enhanced CT of the neck and skull base revealed a midline, infrahyoid, cystic mass with lateral extension; a solid mural nodule with calcification; and adenopathy of the internal jugular chain of lymph nodes with foci of calcifications (Fig 13).
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Figure 13a. Case 4. Contrast-enhanced CT scans obtained at several levels through the neck demonstrate a largely cystic mass anterior to the hyoid bone, extending toward the right. A small focus of calcification (arrow in b) is seen in a soft-tissue mass attached to the wall of the cyst. Enlarged and calcified lymph nodes posterior to the right sternocleidomastoid muscle are also seen.
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Figure 13b. Case 4. Contrast-enhanced CT scans obtained at several levels through the neck demonstrate a largely cystic mass anterior to the hyoid bone, extending toward the right. A small focus of calcification (arrow in b) is seen in a soft-tissue mass attached to the wall of the cyst. Enlarged and calcified lymph nodes posterior to the right sternocleidomastoid muscle are also seen.
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Figure 13c. Case 4. Contrast-enhanced CT scans obtained at several levels through the neck demonstrate a largely cystic mass anterior to the hyoid bone, extending toward the right. A small focus of calcification (arrow in b) is seen in a soft-tissue mass attached to the wall of the cyst. Enlarged and calcified lymph nodes posterior to the right sternocleidomastoid muscle are also seen.
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The patient underwent surgical excision of the neck mass and radical node dissection to debulk the cervical adenopathy. Histologic analysis of the surgical specimens confirmed the diagnosis of a thyroglossal duct cyst with papillary adenocarcinoma (Fig 14).
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Figure 14a. Case 4. (a) Photomicrograph (original magnification, x60; H-E stain) of a specimen taken from the wall of a cystic mass from a different patient reveals thyroid tissue. Small histologic rests of thyroid tissue embedded in the cystic wall are a normal finding in a thyroglossal duct cyst, which arises from persistent anlage of the thyroid gland. (b) Photomicrograph (original magnification, x150; H-E stain) of another specimen from the wall of the thyroglossal duct cyst shows the typical papillary appearance of papillary thyroid adenocarcinoma.
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Figure 14b. Case 4. (a) Photomicrograph (original magnification, x60; H-E stain) of a specimen taken from the wall of a cystic mass from a different patient reveals thyroid tissue. Small histologic rests of thyroid tissue embedded in the cystic wall are a normal finding in a thyroglossal duct cyst, which arises from persistent anlage of the thyroid gland. (b) Photomicrograph (original magnification, x150; H-E stain) of another specimen from the wall of the thyroglossal duct cyst shows the typical papillary appearance of papillary thyroid adenocarcinoma.
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DIAGNOSIS: Thyroglossal duct cyst with a nodule of thyroid tissue containing papillary adenocarcinoma and cervical lymph node metastases.
DISCUSSION
The thyroglossal duct cyst is the most common congenital cystic mass of the neck, representing up to 90% of such lesions. Although they often manifest during childhood, they are also seen in adults. These cysts arise from remnants of the normal developmental anlage of the thyroid gland.
Development of the thyroid gland begins with an epithelial-lined invagination into the base of the tongue at the foramen cecum, at approximately 3 weeks gestation. This thyroglossal duct descends through the tongue mesoderm and passes through the developing tongue muscles, through the floor of the mouth, and anterior to the hyoid bone. The duct then makes a recurrent loop, either through the hyoid or behind it, before finally descending in the anterior neck. By 7 weeks gestation, the thyroid gland usually reaches its normal location, and the duct itself usually regresses by 8–10 weeks gestation. Any interruption of this normal migration can result in either ectopic thyroid tissue or persistence of portions of the thyroglossal duct that can give rise to a cystic mass (Fig 14a).
Most commonly, thyroglossal duct cysts occur below the hyoid bone (65% of cases) (Fig 15); 20% occur at the level of the hyoid bone and 15% above it. The cyst fluid is secreted by the ductal epithelium and accumulates inside the closed pocket. In about one- to two-thirds of thyroglossal duct cysts, functional thyroid tissue exists in the cyst wall. This functioning tissue can be seen at scintigraphy. The persistent thyroid rests within the cyst may develop into carcinoma at roughly the same 4% rate as thyroid tissue within the normally located gland. About 80% of these cancers are papillary thyroid carcinoma, a type that calcifies frequently (Fig 14b). Because of the epithelial lining of the thyroglossal duct cyst, squamous cell carcinomas can also develop.
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Figure 15. Case 4. Sagittal T2-weighted MR image of a different patient illustrates the more typical midline infrahyoid appearance of a thyroglossal duct cyst. The cyst fluid is homogeneously hyperintense.
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The differential diagnosis of cystic neck masses includes infections (bacterial-suppurative or fungal-granulomatous), neoplasms, and other congenital masses. One useful differential feature of thyroglossal duct cysts is that when these cysts occur below the hyoid bone, they are typically embedded within the strap muscles, whereas many other cystic neck masses, such as necrotic lymph nodes and abscesses, are usually more superficial. In addition, thyroglossal duct cysts are usually midline (they are the most common midline neck mass) and branchial cleft cysts are typically lateral, usually related to the anteromedial border of the sternocleidomastoid muscle. Although thyroglossal duct cysts are sometimes septated, they are not as complex as lymphangiomas (cystic hygromas), which are usually multiloculated. The differential diagnosis of calcified neck masses includes granulomatous infections, as well as neoplastic calcifications in papillary adenocarcinomas.
Surgical excision is the treatment of choice, and typically the Sistrunk procedure is recommended. The Sistrunk operation includes removal of the entire tract of the thyroglossal duct cyst, resection of the middle portion of the hyoid bone, and excision of the tongue base. There is no evidence that papillary carcinoma of the thyroglossal duct cyst behaves differently from that in the normal thyroid gland. Preoperative staging may include localization of all functioning thyroid tissue with scintigraphy.
SUGGESTED READINGS
- Bardales RH, Suhrland MJ, Korourian S, Schaefer RF, Hanna EY, Stanley MW. Cytologic findings in thyroglossal duct carcinoma. Am J Clin Pathol 1996; 106:615–619.
- Boswell WC, Zoller M, Williams JS, Lord SA, Check W. Thyroglossal duct carcinoma. Am Surg 1994; 60:650–655.
- Josephson GD, Spencer WR, Josephson JS. Thyroglossal duct cyst: the New York Eye and Ear Infirmary experience and a literature review. Ear Nose Throat J 1998; 77:642–644, 646–647, 651.
- Mahnke CG, Janig U, Werner JA, Rudert H. Primary papillary carcinoma of the thyroglossal duct: case report and review of the literature. Auris Nasus Larynx 1994; 21:258–263.
- Reede DL, Holliday RA, Som PM, Bergeron RT. Nonnodal pathologic conditions of the neck. In: Som PM, Bergeron RT, eds. Head and neck imaging. St Louis, Mo: Mosby, 1991; 531–557.
- Tew S, Reeve TS, Poole AG, Delbridge L. Papillary thyroid carcinoma arising in thyroglossal duct cysts: incidence and management. Aust N Z J Surg 1995; 65:717–718.
- Woodruff WW, Kennedy TL. Non-nodal neck masses. Semin Ultrasound CT MR 1997; 18:182–204.
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CASE 5
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HISTORY
A 43-year-old man was admitted to the hospital 2 weeks after an episode of hemoptysis after a "coughing spell." He had a long history of epistaxis (two to three episodes per day). The chest radiographs obtained at admission had a subtle abnormality (Fig 16). On careful inspection, both the lateral and frontal views demonstrated a faint mass, just above the diaphragm and immediately lateral to the right border of the heart at the level of the right hemidiaphragm.
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Figure 16a. Case 5. Frontal (a) and lateral (b) plain radiographs of the chest demonstrate a subtle opacity overlying the pedicle of the thoracic vertebra, just above the diaphragm on the lateral view (b). On the frontal view (a), the mass is barely visible just to the right of the heart border at the level of the right hemidiaphragm.
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Figure 16b. Case 5. Frontal (a) and lateral (b) plain radiographs of the chest demonstrate a subtle opacity overlying the pedicle of the thoracic vertebra, just above the diaphragm on the lateral view (b). On the frontal view (a), the mass is barely visible just to the right of the heart border at the level of the right hemidiaphragm.
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Further work-up included CT and angiographic examinations. At CT, a bilobate mass with a serpentine connection was seen in the right lower lobe (Fig 17). At angiography, the mass proved to be entirely vascular, with dilated feeding and draining vessels (Fig 18).
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Figure 17a. Case 5. Contrast-enhanced CT scans of the chest (a obtained at a higher level than b) show a bilobed mass with a serpentine connection, located in the medial base of the anterior right lower lobe. The lobed portions of the mass clearly have greater attenuation than any of the soft tissues, including the liver.
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Figure 17b. Case 5. Contrast-enhanced CT scans of the chest (a obtained at a higher level than b) show a bilobed mass with a serpentine connection, located in the medial base of the anterior right lower lobe. The lobed portions of the mass clearly have greater attenuation than any of the soft tissues, including the liver.
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DIAGNOSIS: Pulmonary arteriovenous malformation (AVM) in the setting of hereditary hemorrhagic telangiectasia (HHT).
DISCUSSION
HHT is also known as Osler-Rendu-Weber syndrome. Rendu originally recognized the connection of epistaxis to cutaneous telangiectasia in 1896. Osler added three cases in 1901, and Weber described the familial nature of the cases and the lack of coagulation abnormality. It is not clear how Osler's name became first in the eponym even before Hanes had named the syndrome "hereditary hemorrhagic telangiectasia" in 1909.
There is a controversy regarding whether all pulmonary AVMs are associated with HHT. Estimates of the frequency of this association vary from 36% to 100%. The percentage of patients with HHT who have pulmonary AVMs is less controversial and ranges from 15% to 50%. Pulmonary AVMs may also be associated with cirrhosis and tuberculosis (Rasmussen aneurysm).
Most pulmonary AVMs have pulmonary arterial supply and pulmonary venous drainage with no intervening capillary beds. Although multiple pulmonary AVMs are most typical of HHT, solitary examples certainly occur. The majority of pulmonary AVMs are found in the lower lobes, a location responsible for the characteristic symptom of platypnea (dyspnea with the patient in the upright position because gravity allows the mass to press on the diaphragm).
Most patients with pulmonary AVMs present as asymptomatic young adults: A mass is detected incidently on chest radiographs. Symptoms, if present, can be nonspecific, since hemoptysis occurs in only 10%–15% of patients. Epistaxis is usually seen only in patients with both HHT and pulmonary AVMs and is present in 32%–85% of cases. The epistaxis may be mild to very severe, with up to 45 episodes per month. Many patients report daily epistaxis. Headache is also common in patients with HHT. Cutaneous telangiectasia occurs in up to two-thirds of patients with pulmonary AVMs and is characterized as small, red, vascular blemishes, most frequently on the face, that increase in size and number with age. Complications of pulmonary AVMs include neurologic abnormalities (especially cerebral abscess and other examples of "paradoxical" emboli), hypoxemia, and pulmonary symptoms (especially hemoptysis). Neurologic problems in patients with HHT also include cerebral and spinal AVMs.
The differential diagnosis for the radiographic findings in this case included the five common causes of pulmonary masses: malignancy (primary, metastatic, and lymphomatous), active granulomatous disease, localized inflammation (such as lung abscess or septic emboli), benign neoplasms, and congenital abnormalities. The CT appearance of the mass in this case, especially the high attenuation, favored metastases with high vascularity (such as thyroid carcinoma) and congenital vascular abnormalities, especially pulmonary AVMs. The shape of the serpentine connection between the two masslike lobes strongly favored the diagnosis of pulmonary AVM. In cases in which CT findings are not diagnostic of pulmonary AVMs, a perfusion lung scan may be used to detect a right-to-left shunt. Cardiac US may also be useful when performed with the contrast material indocyanine green. The appearance of this agent is delayed in the left side of the heart. Pulmonary angiography is 100% sensitive in the detection of vessels of 2 mm and larger.
Treatment of pulmonary AVMs, which was originally limited to surgical resection, is now generally embolization. Embolization with coils of various sizes has produced excellent results with no mortality and few complications. The feeding vessel must be 2–3 mm in diameter or larger, and all feeding vessels must be embolized for success. Screening of HHT patients for pulmonary AVMs is very useful in improving prognosis and avoiding complications, especially cerebral abscess and infarction. Because the disease may be inherited, first-degree relatives of patients with pulmonary AVMs should also be screened to avoid a clinical presentation precipitated by neurologic complications. Spiral CT of the chest or clinical evaluation may be used for screening.
SUGGESTED READINGS
- Burke CM, Safai C, Nelson DP, Raffin TA. Pulmonary arteriovenous malformations: a critical update. Am Rev Respir Dis 1989; 134:334–339.
- Goldenberger DM. Pulmonary arteriovenous malformations. In: Fishman AP, ed. Fishman's pulmonary diseases and disorders, 3rd ed. New York, NY: McGraw Hill, 1998.
- Najarian KE, Morris CS. Arterial embolization in the chest. J Thorac Imaging 1998; 13:93–104.
- Osler W. On a family form of recurring epistaxis, associated with multiple telangiectases of the skin and mucous membranes. Bull Johns Hopkins Hosp 1901; 12:333–337.
- Remy J, Remy-Jardin M, Artaud D, Fribourg M. Multiplanar and three-dimensional reconstruction techniques in CT: impact on chest diseases. Eur Radiol 1998; 8:335–351.
- Remy-Jardin M, Wattinne L, Remy J. Transcatheter occlusion of pulmonary arterial circulation and collateral supply: failures, incidents, and complications. Radiology 1991; 180:699–705.
- Weber FP. Multiple hereditary developmental angiomata (telangiectases) of the skin and mucous membranes associated with recurring hemorrhages. Lancet 1907; 2:160–162.
- White RI Jr. Pulmonary arteriovenous malformations: how do we diagnose them and why is it important to do so? Radiology 1992; 182:633–635.
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CASE 6
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HISTORY
A 9-year-old girl with intermittent gross hematuria was brought in for examination. She had a large "birthmark" on her back and three other pigmented lesions, all of which had been noted at previous routine childhood examinations. No similar lesions were seen on her parents or siblings, and her family history was unremarkable. Contrast-enhanced CT and MR imaging performed during the diagnostic work-up revealed an extensive, soft-tissue mass infiltrating the bladder and surrounding the uterus and vagina (Figs 19, 20).
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Figure 19a. Case 6. Axial contrast-enhanced CT scans of the pelvis (obtained at successively higher levels) show a large soft-tissue mass isoattenuated relative to the adjacent skeletal muscle. The mass invades the posterior wall of the bladder (c) and completely surrounds the uterus, vagina, and sigmoid colon (a, b).
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Figure 19b. Case 6. Axial contrast-enhanced CT scans of the pelvis (obtained at successively higher levels) show a large soft-tissue mass isoattenuated relative to the adjacent skeletal muscle. The mass invades the posterior wall of the bladder (c) and completely surrounds the uterus, vagina, and sigmoid colon (a, b).
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Figure 19c. Case 6. Axial contrast-enhanced CT scans of the pelvis (obtained at successively higher levels) show a large soft-tissue mass isoattenuated relative to the adjacent skeletal muscle. The mass invades the posterior wall of the bladder (c) and completely surrounds the uterus, vagina, and sigmoid colon (a, b).
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Figure 20a. Case 6. Sagittal fat-suppressed T1-weighted (a) and fast-spin-echo T2-weighted (b, c) MR images demonstrate the infiltrating mass invading the posterior wall of the bladder, completely surrounding the adjacent uterus and vagina and involving the presacral space. With T2 weighting (c), the mass appears heterogeneously hyperintense relative to muscle.
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Figure 20b. Case 6. Sagittal fat-suppressed T1-weighted (a) and fast-spin-echo T2-weighted (b, c) MR images demonstrate the infiltrating mass invading the posterior wall of the bladder, completely surrounding the adjacent uterus and vagina and involving the presacral space. With T2 weighting (c), the mass appears heterogeneously hyperintense relative to muscle.
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Figure 20c. Case 6. Sagittal fat-suppressed T1-weighted (a) and fast-spin-echo T2-weighted (b, c) MR images demonstrate the infiltrating mass invading the posterior wall of the bladder, completely surrounding the adjacent uterus and vagina and involving the presacral space. With T2 weighting (c), the mass appears heterogeneously hyperintense relative to muscle.
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The patient underwent exploratory laparotomy for evaluation of the pelvic mass. A large tumor consisting of multiple white pearly nodules was found involving the posterior surface of the bladder and surrounding the uterus, rectum, and vaginal wall. Excisional biopsies of the involved pelvic structures were performed and demonstrated the plexiform configuration of the neurofibroma diffusely involving the connective and fibroadipose tissue.
DIAGNOSIS: Plexiform neurofibroma of the genitourinary tract in the setting of neurofibromatosis type 1.
DISCUSSION
Neurofibromatosis is a systemic disease of autosomal dominant inheritance. Tissues and organs primarily of neural crest derivation are typically affected, although almost any tissue can harbor lesions, including those that are classically considered of mesodermal origin. The syndrome is characterized by pigmented cutaneous lesions (cafe au lait spots) and generalized tumors of neural crest origin (mostly neurofibromas and plexiform neurofibromas). Visceral involvement is not frequent, but, when present, it most often involves the gastrointestinal tract. Neurofibroma of the geni
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CASE 1
CASE 2
