Selected References

Lymphomas and Related Disorders

Brandão LA et al: Lymphomas-Part 1. Neuroimaging Clin N Am. 26(4):511-536, 2016

Brandão LA et al: Lymphomas-Part 2. Neuroimaging Clin N Am. 26(4):537-565, 2016

Deckert M et al: Lymphomas. In: Louis DN et al (eds), WHO Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer, 2016, pp 272-277

Diffuse Large B-Cell Lymphoma of the CNS

Citterio G et al: Primary central nervous system lymphoma. Crit Rev Oncol Hematol. 113:97-110, 2017

Lin X et al: Diagnostic accuracy of T1-weighted dynamic contrast-enhanced-MRI and DWI-ADC for differentiation of glioblastoma and primary CNS lymphoma. AJNR Am J Neuroradiol. 38(3):485-491, 2017

Paydas S: Primary central nervous system lymphoma: essential points in diagnosis and management. Med Oncol. 34(4):61, 2017

Koeller KK et al: Extranodal lymphoma of the central nervous system and spine. Radiol Clin North Am. 54(4):649-71, 2016

Todorovic Balint M et al: Gene mutation profiles in primary diffuse large B cell lymphoma of central nervous system: next generation sequencing analyses. Int J Mol Sci. 17(5), 2016

AIDS-Related Diffuse Large B-Cell Lymphoma

Brunnberg U et al: HIV-associated malignant lymphoma. Oncol Res Treat. 40(3):8287, 2017

Carbone A et al: Epstein-Barr virus associated lymphomas in people with HIV. Curr Opin HIV AIDS. 12(1):39-46, 2017

Karia SJ et al: AIDS-related primary CNS lymphoma. Lancet. 389(10085):2238, 2017

Brandão LA et al: Lymphomas-Part 2. Neuroimaging Clin N Am. 26(4):537-565, 2016

Lymphomatoid Granulomatosis

Koeller KK et al: Extranodal lymphoma of the central nervous system and spine. Radiol Clin North Am. 54(4):649-71, 2016

Low LK et al: B-cell lymphoproliferative disorders associated with primary and acquired immunodeficiency. Surg Pathol Clin. 9(1):55-77, 2016

Posttransplant Lymphoproliferative Disorder

Barrantes-Freer A et al: Diagnostic red flags: steroid-treated malignant CNS lymphoma mimicking autoimmune inflammatory demyelination. Brain Pathol. ePub, 2017

Morris J et al: A rare presentation of isolated CNS posttransplantation lymphoproliferative disorder. Case Rep Oncol Med. 2017:7269147, 2017

Degen D et al: Primary central nervous system posttransplant lymphoproliferative disease: an uncommon diagnostic dilemma. Nephrology (Carlton). 21(6):528, 2016

Intravascular (Angiocentric) Lymphoma

Sharma TL et al: Intravascular T-cell lymphoma: a rare, poorly characterized entity with cytotoxic phenotype. Neuropathology. ePub, 2017

Fonkem E et al: Neurological presentations of intravascular lymphoma (IVL): metaanalysis of 654 patients. BMC Neurol. 16:9, 2016

Miscellaneous Rare CNS Lymphomas

Termuhlen AM: Natural killer/T-cell lymphomas in pediatric and adolescent patients. Clin Adv Hematol Oncol. 15(3):200-209, 2017

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(24-59A) NECT of EMH shows several hyperdense nodules along the falx cerebri.

(24-59B) The lobulated lesions are very hypointense on T2WI .

(24-59C) EMH enhances strongly, uniformly as shown on this T1 C+ FS scan in the same patient.

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Gurion R et al: Central nervous system involvement in T-cell lymphoma: A single center experience. Acta Oncol. 55(5):561-6, 2016

Menon MP et al: Primary CNS T-cell lymphomas: a clinical, morphologic, immunophenotypic, and molecular analysis. Am J Surg Pathol. 39(12):1719-29, 2015

MALT Lymphoma of the Dura

de la Fuente MI et al: Marginal zone dural lymphoma: the Memorial Sloan Kettering Cancer Center and University of Miami experiences. Leuk Lymphoma. 58(4):882-888, 2017

Douleh DG et al: Intracranial marginal zone B-cell lymphoma mimicking meningioma. World Neurosurg. 91:676.e9-676.e12, 2016

Metastatic Intracranial Lymphoma

Herr MM et al: Survival of secondary central nervous system lymphoma patients in the rituximab era. Clin Lymphoma Myeloma Leuk. 16(9):e123-e127, 2016

Korfel A et al: How to facilitate early diagnosis of CNS involvement in malignant lymphoma. Expert Rev Hematol. 1-11, 2016

Histiocytic Tumors

Haroche J et al: Histiocytoses: emerging neoplasia behind inflammation. Lancet Oncol. 18(2):e113-e125, 2017

Paulus W et al: Histiocytic tumors. In: Louis DN et al (eds), WHO Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer, 2016, pp 280-283

Ranganathan S: Histiocytic proliferations. Semin Diagn Pathol. 33(6):396-409, 2016

Langerhans Cell Histiocytosis

Porto L et al: Central nervous system imaging in childhood Langerhans cell histiocytosis - a reference center analysis. Radiol Oncol. 49(3):242-9, 2015

Erdheim-Chester Disease

Estrada-Veras JI et al: The clinical spectrum of Erdheim-Chester disease: an observational cohort study. Blood Adv. 1(6):357-366, 2017

Martineau P et al: The imaging findings of Erdheim-Chester disease: a multimodality approach to diagnosis and staging. World J Nucl Med. 16(1):71-74, 2017

Rosai-Dorfman Disease

Joshi SS et al: Cranio-spinal Rosai Dorfman disease: case series and literature review. Br J Neurosurg. 1-8, 2017

Luo Z et al: Characteristics of Rosai-Dorfman disease primarily involved in the central nervous system: 3 case reports and review of literature. World Neurosurg. 97:58-63, 2017

Juvenile Xanthogranuloma

Meshkini A et al: Systemic juvenile xanthogranuloma with multiple central nervous system lesions. J Cancer Res Ther. 8(2):311-3, 2012

Histiocytic Sarcoma

Jiang M et al: Lymphoma classification update: T-cell lymphomas, Hodgkin lymphomas, and histiocytic/dendritic cell neoplasms. Expert Rev Hematol. 10(3):239-249, 2017

Zanelli M et al: Primary histiocytic sarcoma presenting as diffuse leptomeningeal disease: case description and review of the literature. Neuropathology. ePub, 2017

Hemophagocytic Lymphohistiocytosis

Cai G et al: Central nervous system involvement in adults with haemophagocytic lymphohistiocytosis: a single-center study. Ann Hematol. 96(8):1279-1285, 2017

Hematopoietic Tumors and Tumor-Like Lesions

Keraliya AR et al: Imaging of nervous system involvement in hematologic malignancies: what radiologists need to know. AJR Am J Roentgenol. 205(3):604-17, 2015

Leukemia

Frishman-Levy L et al: Advances in understanding the pathogenesis of CNS acute lymphoblastic leukaemia and potential for therapy. Br J Haematol. 176(2):157-167, 2017

Murthy H et al: Diagnosis and management of leukemic and lymphomatous meningitis. Cancer Control. 24(1):33-41, 2017

Ranta S et al: Role of neuroimaging in children with acute lymphoblastic leukemia and central nervous system involvement at diagnosis. Pediatr Blood Cancer. 64(1):64-70, 2017

Arber DA et al: The 2016 revision to the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia. Blood. 127(20):2391-405, 2016

Guenette JP et al: MRI findings in patients with leukemia and positive CSF cytology: a single-institution 5-year experience. AJR Am J Roentgenol. 1-5, 2016

Plasma Cell Tumors

Paludo J et al: Myelomatous involvement of the central nervous system. Clin Lymphoma Myeloma Leuk. 16(11):644-654, 2016

Wilberger AC et al: Intracranial involvement by plasma cell neoplasms. Am J Clin Pathol. 146(2):156-62, 2016

Extramedullary Hematopoiesis

van der Bruggen W et al: PET in benign bone marrow disorders. Semin Nucl Med. 47(4):397-407, 2017

Roberts AS et al: Extramedullary haematopoiesis: radiological imaging features. Clin Radiol. 71(9):807-14, 2016

The sellar region is one of the most anatomically complex areas in the brain. It encompasses the bony sella turcica and pituitary gland plus all the normal structures that surround it. Virtually any of these can give rise to pathology that ranges from incidental and innocuous to serious, potentially life-threatening disease.

At least 30 different lesions occur in or around the pituitary gland, arising from either the pituitary gland itself or the structures that surround it. These include the cavernous sinus and its contents, arteries (the circle of Willis), cranial nerves, meninges, CSF spaces (the suprasellar cistern and third ventricle), central skull base, and brain parenchyma (the hypothalamus).

Despite the overwhelming variety of lesions that can occur in this region, at least 75-80% of all sellar/juxtasellar masses are due to one of the "Big Five": macroadenoma, meningioma, aneurysm, craniopharyngioma, and astrocytoma. All other lesions combined account for less than one-quarter of sellar region masses. Entities such as germinoma, Rathke cleft cyst, and hypophysitis each cause 1-2% or less.

Some authors recommend using a mnemonic (such as SATCHMO for sarcoid, aneurysm or adenoma, teratoma or tuberculosis, craniopharyngioma or cyst, hypophysitis or hamartoma or histiocytosis, meningioma or metastasis, and optic glioma) to remember the spectrum of lesions that can occur in/around the sella. However, this list mixes rare with common lesions and is unhelpful in establishing a clinically tailored, radiologically appropriate differential diagnosis.

The previous chapters in this section focus on specific neoplasms as defined histopathologically. This chapter is different. Its focus is geography and location. The goal of this discussion is to present the anatomy of the sellar region and then discuss the various lesions that make their home in this anatomically varied "neighborhood."

We begin the chapter with a general overview that includes keys to diagnosis, clinical considerations, and helpful findings on imaging studies. We then consider the normal gross and imaging anatomy of the sellar region.

Next we discuss normal variants such as physiologic hypertrophy that can mimic pituitary pathology. Congenital lesions (such as tuber cinereum hamartoma) that can be mistaken for more ominous pathology are also delineated. Pituitary gland and infundibular stalk neoplasms are then discussed. A brief consideration of miscellaneous lesions such as lymphocytic hypophysitis, pituitary apoplexy, and the postoperative sella follows.

The goal of imaging is to determine precisely the location and characteristics of a sellar mass, delineate its relationship to—and involvement

(25-1) Midline anatomic section depicts sella and surrounding structures. Adenohypophysis , neurohypophysis are shown, along with the optic chiasm and optic and infundibular recesses of the third ventricle. (Courtesy M. Nielsen, MS.)

with—surrounding structures, and construct a reasonable, limited differential diagnosis to help direct patient management. We then conclude the chapter with a summary of—and approach to—a differential diagnosis of sellar masses.

When you finish this discussion, you should be able to look at an unknown sellar mass and offer a focused differential diagnosis, not simply a recital of all the possible lesions that can be found in this anatomically complex region!

Diagnostic Considerations

Anatomic sublocation is the single most important key to establishing an appropriate differential diagnosis of a sellar region mass. The first step is assigning a lesion to one of three anatomic compartments, identifying it as an (1) intrasellar, (2) suprasellar, or (3) infundibular stalk lesion.

The key to determining anatomic sublocation accurately is the question, "Can I find the pituitary gland separate from the mass?" If you can't, and the gland is the mass, the most likely diagnosis is macroadenoma.

If the mass is clearly separate from the pituitary gland, it is extrapituitary and therefore not a macroadenoma. Other pathologies such as meningioma in an adult or craniopharyngioma should be considered in such cases.

Clinical Considerations

The single most important clinical feature in establishing an appropriate differential diagnosis for a sellar region mass is patient age. Lesions that are common in adults (macroadenoma, meningioma, and aneurysm) are generally rare in children. A lesion in a prepubescent child—especially a

(25-2) Photomicrograph of a sectioned normal pituitary gland shows Rathke pouch remnant as a "cleft" between the anterior and posterior lobes of the pituitary gland. (Courtesy A. Ersen, MD, B. Scheithauer, MD.)

boy—that looks like a macroadenoma is almost never a neoplasm. Nonneoplastic pituitary gland enlargement in children is much more common than tumors. Therefore, an enlarged pituitary gland in a child is almost always either normal physiologic hypertrophy or nonphysiologic nonneoplastic hyperplasia secondary to end-organ failure (most commonly hypothyroidism).

Some lesions that are common in children (e.g., opticochiasmatic/hypothalamic pilocytic astrocytoma and craniopharyngioma) are relatively uncommon in adults.

Sex is also important. Imaging studies of young menstruating female patients and postpartum women often demonstrate plump-appearing pituitary glands due to temporary physiologic hyperplasia.

Imaging Considerations

Imaging appearance is very helpful in evaluating a lesion of the sellar region. After establishing the anatomic sublocation of a lesion, look for imaging clues. Are other lesions present? Is the lesion calcified? Does it appear cystic? Does it contain blood products? Is it focal or infiltrating? Does it enhance? Does it enlarge or invade the sella turcica?

Sellar Region Anatomy

We briefly review the normal gross and imaging anatomy of the sellar region. Understanding normal anatomy forms the foundation for our subsequent consideration of sellar neoplasms and tumor-like lesions, the major topics of this chapter.

(25-3) Coronal gross section shows important structures adjacent to the pituitary gland . Cavernous , supraclinoid internal carotid arteries (ICAs) are shown, as are the diaphragma sellae and optic nerves . (Courtesy M. Nielsen, MS.)

Gross Anatomy

Bony Anatomy

The sella turcica ("Turkish saddle") is a midline concavity in the basisphenoid of the central skull base that contains the pituitary gland. The sella is entirely embedded within the sphenoid bone. The anterior borders of the sella are formed by the tuberculum sellae and anterior clinoid processes of the lesser sphenoid wing, whereas the posterior border is formed by the dorsum sellae. The top of the dorsum sellae expands slightly posteriorly and laterally to form the posterior clinoid processes, which in turn form the upper margin of the clivus

(25-1).

The sellar floor is part of the sphenoid sinus roof, which is partially or completely aerated. The cavernous segments of the internal carotid arteries lie in shallow bony grooves (the carotid sulci) located inferolateral to the pituitary fossa (25- 3).

Meninges

The meninges in and around the sella form important anatomic landmarks. Dura covers the bony floor of the sella, separating it from the pituitary gland. A thin dural reflection borders the pituitary fossa laterally and forms the medial cavernous sinus wall.

A small circular dural shelf, the diaphragma sellae (25-3), forms a roof over the sella that almost covers the pituitary gland. The diaphragma sellae has a variably sized central opening, the diaphragmatic hiatus, that transmits the pituitary stalk (25-5). The mean diameter of the diaphragmatic hiatus is 7 mm.

(25-4) Cranial nerves in the lateral dural wall of cavernous sinus include CNs III , IV , V , and V . Only CN VI is inside the cavernous sinus itself.

A prominent basal arachnoid membrane, called the Liliequist membrane, forms trabeculae that cross the suprasellar cistern and cover the hypothalamus and diaphragma sellae. A sleeve of arachnoid reflects over the pituitary stalk, forming a thin hypophyseal cistern that can provide a surgical dissection plane in approaching suprasellar masses.

Pituitary Gland

The pituitary gland, also called the hypophysis, is a reddishgray, bean-shaped gland with two distinct parts (sometimes called "lobes"): the anterior pituitary, also called the adenohypophysis (AH), and the posterior pituitary or neurohypophysis (NH) (25-40).

The anterior and posterior pituitary lobes differ in embryologic origin, structure, and function but are joined together into a single gland, the hypophysis.

Anterior Pituitary Gland (Adenohypophysis). The AH, formerly called the anterior lobe, accounts for 75-80% of the total pituitary gland volume. The AH wraps anterolaterally around the NH in a U-shaped configuration. The AH is subdivided into three parts: the pars distalis (pars anterior), pars intermedia, and pars tuberalis.

The AH develops as an outgrowth—called Rathke pouch—of embryonic ectoderm that lines the roof of the buccal cavity (25-2). This outgrowth subsequently detaches from the buccal cavity, and its anterior wall thickens to become the largest part of the AH called the pars distalis. The posterior wall differentiates into the pars intermedia, whereas the dorsolateral portions extend around the infundibulum as the pars tuberalis.

(25-5) Axial graphic depicts the pituitary gland and stalk from above seen through the opening of the diaphragma sellae.

All three parts of the AH produce hormones. Most are tropins that regulate the function of other endocrine cells such as secretary cells in the gonads, thyroid, and adrenal cortex. All of the anterior pituitary hormones are regulated by hypothalamic-releasing hormones except prolactin (PRL), which is under the control of a dopaminergic circuit.

Cells in the pars distalis of the AH produce five different hormones: somatotropin (also known as growth hormone or GH), PRL, thyroid-stimulating hormone, follicle-stimulating hormone/luteinizing hormone (FSH/LH), and adrenocorticotrophic hormone (ACTH). In addition, the AH also has a substantial proportion of cells that do not express hormonal markers. These non-hormone-secreting cells are called chromophobes.

The pituitary gland of newborns already presents a full set of terminally differentiated hormone-producing cells. However, the postnatal gland undergoes extensive remodeling. Soon after birth, the AH enters a dramatic growth phase that significantly increases the size of the gland.

The adult pituitary gland can adapt its cellular composition in response to changing physiologic conditions.

Posterior Pituitary Gland (Neurohypophysis). The posterior pituitary or NH develops from the embryonic diencephalon (forebrain) as a downward extension of the hypothalamus. The posterior pituitary is subdivided into a large pars nervosa and smaller infundibulum (pituitary stalk).

The NH comprises 20-25% of the overall pituitary gland volume. The NH remains attached to the brain via the infundibulum, which inserts into the median eminence of the hypothalamus.

(25-6) Sagittal graphic depicts cranial nerves of the cavernous sinus lateral to the pituitary gland and stalk . Meckel cave is filled with CSF and contains fascicles of CN V and the gasserian (semilunar) ganglion .

Most of the pars nervosa parenchyma consists of axonal terminations of neurons whose cell bodies are located in the hypothalamus. Neurons constitute approximately 75% of the posterior lobe. The remaining 25% of the posterior lobe consists of glial cells called pituicytes.

There are no intrinsic hormone-producing cells in the pars nervosa or pituitary stalk. Instead, the pars nervosa secretes two hormones that are formed in the hypothalamus: antidiuretic hormone (also called vasopressin) and oxytocin. Both hormones are synthesized as a larger precursor prohormone that also contains a carrier protein, neurophysin. The prohormone is transported down the axons of the hypothalamo-hypophyseal tract in the infundibulum, cleaved to its active form in the NH, and stored as secretory granules in the axon terminals.

Blood Supply

Arteries. Two sets of branches arise from the internal carotid arteries (ICAs) to supply the neurohypophysis. Single inferior hypophyseal arteries arise from the cavernous ICAs and supply most of the neurohypophysis. Several superior hypophyseal arteries arise from the supraclinoid ICAs with smaller contributions from the anterior and posterior cerebral arteries. The superior hypophyseal arteries mostly supply the median eminence of the hypothalamus and infundibular stalk.

There is no direct arterial supply to the AH.

Veins. The hypophyseal portal system consists of a primary capillary plexus in the median eminence of the pituitary hypothalamus and infundibulum and a secondary capillary plexus in the pars distalis of the AH. These are connected by long hypophyseal portal veins. Venous blood from both the

The portal system forms an essential link between the hypothalamus and endocrine system; it is the route by which hypothalamic releasing and inhibitory hormones reach their target cells in the pars distalis of the AH to control pituitary function. The portal system also carries hypophyseal hormones from the gland to their endocrine targets and facilitates feedback control of secretion.

Hypothalamus and Third Ventricle

The hypothalamus lies directly above the pituitary gland, extending posteriorly from the lamina terminalis (anterior wall of the third ventricle) to the mammillary bodies. The tuber cinereum is part of the hypothalamus. It is the thin convex mass of gray matter that lies between the optic chiasm anteriorly and the mammillary bodies posteriorly. The infundibular stalk extends inferiorly from the tuber cinereum, gradually tapering as it descends to become continuous with the posterior pituitary lobe.

The third ventricle lies in the midline just above the hypothalamus. Two CSF-filled recesses of the third ventricle, the optic and infundibular recesses, project inferiorly toward the hypothalamus. The optic recess is more rounded and lies just in front of the optic chiasm. The infundibular recess is more conical and pointed, extending into the upper part of the pituitary stalk (25-7A).

Cavernous Sinus, Cranial Nerves

Cavernous Sinus. The cavernous sinuses (CSs) are irregularly shaped, trabeculated venous compartments that lie along the lateral aspects of the sella turcica. The CSs are contained within a prominent lateral and a thin (often inapparent) medial dural wall. Important CS contents include the cavernous ICA segments and several cranial nerves.

Cranial Nerves. Here we briefly review the cranial nerves that course through the cavernous sinus. (Anatomy of all the cranial nerves is discussed in detail in Chapter 23.)

The abducens cranial nerve (CN VI) is the only cranial nerve that actually lies within the CS, inferolateral to the cavernous ICA. Cranial nerves III, IV, V , and V all lie within the lateral dural wall (25-4). The oculomotor nerve (CN III) is the most cephalad of the cavernous cranial nerves and is contained within a thin sleeve of CSF-filled arachnoid called the oculomotor cistern. The trochlear nerve (CN IV) lies just inferior to CN III.

Two divisions of the trigeminal nerve (CN V), the ophthalmic (V ) and maxillary (V ) divisions, lie inferior to the trochlear nerve. The mandibular nerve (CN V ) does not enter the CS. The trigeminal ganglion lies within another arachnoid-lined CSF space, Meckel cave. CN V exits inferiorly from the trigeminal (gasserian or semilunar) ganglion and passes through the foramen ovale into the masticator space (25-6).

Technical Considerations

Appropriate imaging of the hypothalamic-pituitary axis is based on specific endocrine testing as suggested by clinical signs and symptoms. Thin-section (2-3 mm) multiplanar MR with a small field of view obtained before and after contrast administration, including dynamic as well as static sequences, is the best imaging procedure for hypothalamic-pituitary axis abnormalities (25-7). CTA, MRA, DSA, and petrosal sinus sampling are supplemental techniques in selected cases.

Contrast-enhanced CT occasionally facilitates diagnosis of neuroendocrine abnormalities but is less sensitive than MR. Bone CT may be helpful in depicting the extent of bony involvement with invasive adenomas or differentiating lesions that arise in the basisphenoid.

Pituitary Size and Configuration

Overall height of the pituitary gland on coronal T1-weighted MR scans varies with both age and sex. In prepubescent children, 6 mm or less is normal. The upper limit of normal in men and postmenopausal women is 8 mm.

Physiologic hypertrophy during puberty and young menstruating female patients is common, with normal gland height reaching 10 mm. Pregnant and postpartum lactating female patients have even larger, superiorly convex pituitary glands that may measure up to 12-14 mm in height.

The infundibular stalk measures approximately 3-4 mm in diameter at the level of the optic chiasm and gradually tapers to about 2 mm as it descends to its insertion into the pituitary gland (25-7F).

Signal Intensity of the Pituitary Gland

Pituitary gland signal intensity varies. With the exception of neonates (in whom the AH can be large and very hyperintense), the AH is typically isointense compared with cortex on both T1and T2WI. The NH usually has T1 shortening (the so-called posterior pituitary "bright spot") caused by the presence of neurosecretory granules. The posterior pituitary "bright spot" does not contain lipid and does not suppress on fat-suppression techniques (25-7E). Up to 20% of endocrinologically normal patients lack a posterior pituitary "bright spot."

The infundibular stalk is isointense with the pituitary except for a central hyperintensity on T2WI. The infundibular recess of the third ventricle extends inferiorly into the stalk for a variable distance.

Enhancement Patterns

The pituitary gland does not have a blood-brain barrier, so it enhances rapidly and intensely following contrast administration. Pituitary gland enhancement is slightly less intense than that of venous blood in the adjacent cavernous sinuses (25-7D).