This document discusses the diagnosis of pituitary tumors through laboratory evaluation. It begins by describing the anatomy and functions of the pituitary gland. Symptoms of pituitary disease are then outlined, including those related to hyperpituitarism and hypopituitarism. The document then discusses various pituitary tumor types, providing details on histology, immunohistochemistry, classification, and diagnostic approach. Specific tumor types covered in depth include prolactinomas, growth hormone-producing adenomas, and ACTH-producing adenomas associated with Cushing's disease. Diagnostic testing for Cushing's disease including urine cortisol and dexamethasone suppression testing is summarized.

1. LAB DIAGNOSIS OF PITUITARY
TUMORS
FROM -DR. GARGI TIGNATH
GUIDED BY -DR. PURTI AGRAWAL

2. INTRODUCTION
Pituitary gland is a small, bean-shaped structure ,lies at the base of the
brain within the confines of the sella turcica.
 Intimately related to the hypothalamus, connected by both a stalk,
composed of axons extending from the hypothalamus & rich venous
plexus constituting a portal circulation.
Along with hypothalamus, has a central role in the regulation of most of
the other endocrine glands.
composed of two morphologically and functionally distinct components:
1.Anterior lobe (adenohypophysis)
2.posterior lobe (neurohypophysis).

6. SYMPTOMS AND SIGNS OF PITUITARY DISEASE CAN BE
GROUPED AS FOLLOWS:
Hyperpituitarism-related effects:
Hyperpituitarism arises from excessive secretion of trophic hormones.
Most often results from an anterior pituitary adenoma but also may be
caused by other pituitary and extrapituitary Lesions.
Hypopituitarism-related effects:
 Nonfunctional pituitary adenomas may encroach upon and destroy
adjacent normal anterior pituitary parenchyma, causing hypopituitarism.

7. Local mass effects:
Radiographic abnormalities of the sella turcica, including sellar
expansion, bony erosion, and disruption of the diaphragma sellae.
close proximity of the optic nerves and chiasm to the sella-
expanding pituitary lesions -compress decussating fibers in the optic
chiasm.
Defects in the lateral (temporal) visual fields—-called bitemporal
hemianopia.

9. Pituitary macroadenoma-Thinning and demineralization of the sellar floor, as well as
suprasellar extension, are seen.

10. NORMAL HISTOLOGY OF PITUITARY GLAND
Normal anterior pituitary. Note the variation in cellular granularity. The
staining ranges from acidophilic to chromophobic; several dark-staining
basophils are also present.

11. Posterior pituitary- consists of the axonal processes and terminations of the
vasopressin and oxytocin-producing supraoptic and paraventricular nuclei.
In addition, endothelial cells and pituicytes, modified astrocytes, contribute
to its cellularity

12. Normal anterior pituitary. Acini and cords of cells are demonstrated
(reticulin stain).

13. Pituitary tumors
Account for 10-25 % of brain tumors
Medium age : between 20-50 years
Children rarely have pituitary adenomas.
Most tumor in children are craniopharyngiomas and are associated
with growth failure and diabetes insipidus.
Most pituitary adenomas in children are prolactinomas
In women Prolactinomas, GH secreting adenomas and ACTH-
secreting adenomas are more frequent.
In men GH secreting adenomas are more frequent.

14. HISTOGENESIS OF PITUITARY TUMORS
Two hit hypothesis:
Pituitary adenomas are monoclonal tumors
Polyclonal adenomas may result from excessive stimulation of pituitary
by specific releasing hormones
Pituitary cells have a genetic protective factor against tumor
proliferation.
Lost of one protective allelle - first hit is not associated with tumor
transformation, a point mutation of the second allelle – second hit results
in tumor proliferation .
Tumor occurs only if both protective factors are lost

15. PITUITARY TUMORS - CLASSIFICATION
According to their size:
Microadenomas: have <1 cm, do not modify the shape of sella
turcica and do not produce pituitary tumor syndrome
Macroadenomas: have > 1 cm. and according to the direction they
develop produce “the syndrome of pituitary tumors”
According to their degree of aggression
Benign adenomas
Invasive adenomas
Carcinomas: less then 1 % of pituitary tumors

16. Pituitary macroadenoma

17. Microadenoma

19. Microadenoma- Relative circumscription and early compression of
surrounding parenchyma are seen, acinar architecture is effaced

20. Pituitary adenoma-lack of reticulin content and the compression of
surrounding parenchyma are demonstrated (reticulin stain).

21. Pituitary adenomas- H&E-staining shows -Diffuse (A), papillary (B), ribbon (C), and
pleomorphic (D) patterns, illustrates their broad morphologic spectrum and
highlights the diagnostic use of immunohistochemistry.

22. CLASSIFICATION OF PITUITARY ADENOMAS

23. FAMILIAL PITUITARY TUMOR SYNDROMES

24. PITUITARY TUMOR SYNDROME
NEUROLOGIC SYMPTOMS:
Headache
Nerves III, IV and VI which cross the cavernous sinus
Temporal seizures
Other seizures
Meningeal signs
OPHTHALMOLOGIC SIGNS:
Decreased visual acuity
Reduction of visual field according to tumor extension
Exophtalmos : rare
RADIOLOGICAL SIGNS:
Enlarged surface of sella turcica
Radiologic signs specific for some pituitary adenomas:
acromegaly

25. APPROACH TO DIAGNOSIS

26. 1.Clinical evaluation of pituitary adenoma
2.Radiological evaluation of suprasellar mass- MRI/CT
3.Ophthalmic evaluation
4.Laboratory investigations-
-Initial hormonal evaluation-
-Basal prolactin
-Insulin like growth factor
-24hr urinary free cortisol(UFC)/overnight oral dexamethasone(1mg)
suppression test
-ᾳ subunit FSH&LH
-Thyroid function test

27. 5.Histological evaluation-
Routine H&E Sections
Histochemical staining:
-Periodic acid-Schiff (PAS), Reticulin stain
Immunohistochemistry:
-PRL,ACTH,GH,TSH, LH, FSH, ± α-subunit,
EMA,cytokeratin(ck),chromogranin
Electron microscopy(ultrastructural changes)

28. PROLACTIN CELL ADENOMA
Prolactinomas are the most frequently occurring adenoma in MEN1
Microadenomas generally occur in reproductive-age women
In men and postmenopausal women, often appear to be clinically
nonfunctional, growing to macroadenoma dimensions and exhibiting invasion .
50% of prolactinomas are grossly or radiographically invasive at initial surgery
Frequency of invasion increases with tumor size
Serum PRL levels are uniformly elevated in patients with prolactinoma

29. LACTOTROPH ADENOMAS ARE OF TWO
TYPES:
Sparsly Granulated-25%
Densly Granulated-1%
C/F-Amennorhea
-Galactorrhea
-Impotence, loss of Libido
DIAGNOSIS:
BLOOD HORMONE LEVELS-↑↑↑ PROLACTIN LEVELS, little more than
normal (approximately 20 ng/mL) to extremely high (≥2000 ng/mL)

30. HISTOPATHOLOGY-
Gross-1.Microadenomas-33%
2.macroadenomas-67%
Microscopy: –Sparsly granulated-chromophobic
-Densly granulated-Mostly-Eosinophilic
10 to 20%-microcalcification.
-HISTOCHEMICAL STAINING :A-C (densely to sparsely granulated); eosin,
phloxine; orange G
-IMMUNOREACTION:+ for PRL

31. (A)Prolactin cell adenomas are nearly all chromophobic, and they often contain
spherical microcalcifications.
(B)IHC: Prolactin shows a characteristic globular reaction in the paranuclear Golgi
zone.

32. DIAGNOSIS:
-EM : Abundant rich ER, misplaced exocytosis between neoplastic cells
-TREATMENT-Medical-Dopamin agonist.
-Surgical-for macroadenomas.
-DIFFERENTIAL DIAGNOSIS-Acidophil stem cell adenoma.

33. (A)Prolactinoma with amyloid deposition. (B) polarization Such spherical bodies are
virtually diagnostic of a prolactin cell adenoma

34. (A)Prolactin cell adenoma-sparsly granulated-Abundant RER and golgi
apparatous and misplaced exocytosis
(B)PRL Adenoma treated with bromocriptine,hyperchromatic nuclei,small
cell,cytoplasm contains scanty organelles.

35. GROWTH HORMONE-PRODUCING ADENOMAS
SOMMATOTROPHS:
25% of adenomas are associated with clinical or immunocytologic evidence of GH
production,
only a minority makes GH alone,vast majority of adenomas produce both GH and
PRL or are plurihormonal, also expressing TSH and/or α-subunit
Precursor lesions of GH cell adenomas include :
somatotroph hyperplasia caused by ectopic production of growth hormone-
releasing hormone (GHRH) by :
Endocrine tumors in the McCune-Albright syndrome
GH adenomas in Carney complex
Sparsely granulated-5%
Densely granulated-5%

37. C/F: Acromegaly or gigantism
DIAGNOSIS
-BLOOD HORMONES:↑↑GH
-SCREENING TESTS FOR FUNCT IONAL GH ADENOMAS
Acromegaly -Serum IGF-IOral glucose tolerance test with GH obtained
at 0, 30, and 60 min
Interpret IGF-I relative to age and sex-matched controls
Normal subjects should suppress growth hormone to <1 g/L
Exclude medications,MRI of the sella should be
ordered if PRL is also elevated.

38. The increased height and prognathism (A) and enlarged hand (B) and foot (C) of
the affected twin are apparent. Their clinical features began to diverge at the age
of approximately 13 years.

39. HISTOPATHOLOGY:
-GROSS:14% micro/86% macro
-MICROSCOPY: C-A
-IMMUNOREACTION: + FOR GH
-INVASION:50% overall(chromophobic>eosinophillic tumors)
-TREATMENT:Long standing somatostatin analogs like octreotide

40. MICROSCOPY:
A) Growth hormone cell adenoma, sparsely granulated (chromophobic) type.
Note the presence of paranuclear hyaline bodies. (B) Immunoreactivity for
growth hormone may be weak and present in only a portion of cells

41. (A)Growth hormone (GH) cell adenoma, densely granulated (eosinophilic) type,
prominent acidophilia &Lack of fibrous bodies.
(B) GH immunoreactivity is strong

42. Densly granulated GH adenoma with numerous large
secretary granules 200 t0 600 nm diameter.
EM:

43. Sparsly granulated GH Adenoma with scant small granules
(400-450 nm)and fibrous bodies trapping secretary granules
,mitochondria and few lysosomes.

44. ADENOMAS WITH COMBINED LACTOTROPIC AND
SOMATOTROPIC FEATURES
1.Mixed GH cell/PRL cell(5%)- both A/C
2.Mammosomatotroph(3%)-A(GH/PRL/TSH)
3.Acidophil stem cell(1%)-C

45. C/F-
Acromegaly or gigantism
± hyperprolactinemia(Amennorhea,Galactorrhea,Impotence, loss of Libido)
DIAGNOSIS:
BLOOD HORMONE LEVELS: ↑GH/PRL
HISTOPATHOLOGY: GROSS:
Mixed GH cell/PRL cell- 26% micro/74% macro ,Overall Invasion-31%
Mammosomatotroph- 50% micro/50% macro
Acidophil stem cell-Usually invasive macroadenomas
IMMUNOREACTION:+ FOR GH/PRL

46. ELECTRON MICRSCOPY:
Mixed growth hormone cell-prolactin cell adenoma
-Variable proportions of sparsely and densely granulated growth hormones and
prolactin cells
Mammosomatotroph cell adenoma:
cell-
Prominent, numerous immature secretory vesicles
Two populations of granules:
150-450 nm, electron dense, round to oval, apposed limiting membrane;
350-2000 nm, variably electron dense,elongated, loose limiting membrane
(intracellular and extracellular); abundant

47. Mixed growth hormone (GH) cell-prolactin (PRL) cell
adenomas
Such tumors consist of two distinct cell populations, one of which is reactive for
GH (A) and one of which is reactive for PRL (B).

48. Mixed adenoma showing sparsly granulated PRLcells and
densly granulated GH Cell,Note RER& large golgi bodies.

49. ACIDOPHIL STEM CELL ADENOMA
Although definitive diagnosis of this uncommon lesion requires IHC and EM,
H&E stains may show paranuclear vacuolization, a feature corresponding to
giant mitochondria

50. Acidophil stem cell adenoma:
EM:
Moderate; few associated secretory granules
granule morphology:50-300 nm, electron dense; sparse
Paranuclear fibrous bodies, SER, multiple centrioles, misplaced exocytosis,
frequent abnormal or giant mitochondria, variable oncocytic transformation

51. Acidophilic stem cell adenoma:showing oncocytic change with
giant mitochondria

52. CORTICOTROPH CELL ADENOMAS
Adenomas that produce ACTH fall into Four major
groups:
Endocrinologically active tumors associated with either
Cushing disease
Nelson syndrome
Clinically nonfunctioning or silent corticotropic adenomas.
Crook cell adenoma

53. Hypothalamoadrenal axis(HPA)

54. CUSHING DISEASE
Although Cushing disease is rarely caused by corticotroph cell hyperplasia,
the vast majority of cases are caused by an ACTH-producing adenoma.
Incidence of the disease is-1 to 10 cases per million per year.
3.5% of cases occur in the setting of MEN1
Isolated familial Cushing disease is very rare
ACTH-producing tumors represent nearly 15% of all adenomas.
peak incidence is 30 to 40 years
Female-to-male ratio is 8:1.

55. .
A low value, especially after corticotropin-releasing hormone (CRH) stimulation,
indicates an extrapituitary source.
15% to 20% of all ACTH cell adenomas are found to be invasive
Postoperative remission is achieved in 90% of microadenomas but only 65% of
macroadenomas

56. C/F- Hypercortisolism

57. DIAGNOSIS:
1.Clinical sign and symptoms
2.Radiological evidence of supra sellar mass-CT/MRI
3.Blood hormone levels-ACTH, Blood ACTH levels may be high but are generally
less than 200 pg/mL(normal range4-22pg/l)
-Screening Tests for Cushing’s disease
-24-h urinary free cortisol-(UFC)-is precise and cost effective,ensure urine
collection is total and accurate.
-Dexamethasone suppression test-(1 mg),at 11 p.m. and fasting plasma cortisol
measured at 8 a.m. -Normal subjects suppress to<5 g/dL
-Basal plasma-ACTH assay
-Distinguishes adrenal adenoma (ACTH suppressed)from ectopic ACTH or(pituitary
adenoma,Cushing’s disease (ACTH normal or elevate)

58. -Inferior petrosal sinus sampling(IPSS) –Sampling is performed at baseline
and 2, 5, and 10 min after intravenous bovine CRH (1 μg/kg) injection
-Basal inferior petrosal:peripheral vein ACTH ratio (>2)-
confirms pituitary Cushing’s syndrome.
-After CRH injection, peak petrosal:peripheral ACTH ratios ≥3 confirm the
presence of a pituitary ACTH-secreting tumor.

59. 4.LM: GROSS:ACTH adenomas are amphophilic or basophilic (87%) are
- Microadenomas 87%(mean size, 5 mm),
-Invasion ,microadenomas (8%) than in macroadenomas (62%)
- Extratumoral pituitary typically shows Crooke hyaline change, which is the
result of massive perinuclear accumulation of cytokeratin filaments
5.HISTOCHEMICAL STAINING:PAS positive
(A) Amphophilic and granule rich (B) periodic acid-Schiff positive

60. ACTH ADENOMAS
Crooke hyaline change in the corticotropic cells is a regular accompaniment of
ACTH-producing adenomas,peripherally situated hyaline band (left) is composed of
cytokeratin, and thus, it is not ACTH immunoreactive (right).

61. Corticotroph Adenoma Showing Crook’s Hyalinization most of the
cytoplasm replaced by thick rim of cytokeratin filaments displacing
secretary granules to cell periphery.

62. 6.IHC:+ ACTH, pro-opiomelanocortin (POMC), precursor molecule{ β-lipotropin,
endorphin, enkephalins, and melanocyte-stimulating hormone (MSH)}
7.EM:
Abundance of secretory granules
perinuclear cytoplasmic intermediate filament bundles composed of keratin .
Their presence explains the variable cytokeratin immunoreactivity of corticotropic
adenomas.

63. NELSON SYNDROME
 Incidence-2%
Lesion underlying this disorder, undetectable by radiographic means and thus
prompting an adrenalectomy. (To control hypercortisolism and cushings syndrome)
Continued tumor growth is then furthered by lack of inhibitory feedback effects of
glucocorticoids.
Most are invasive macroadenomas
Unlike cushing adenoma,these are variably PAS positive,crook hyaline change is
lacking.

64. BLOOD HORMONE LEVELS-↑ACTH, β-LPH, endorphins, and POMC
LM:, GROSS:100% macro, MICROSCOPY: B-C
82% INVASION
HISTOCHEMICAL REACTION:variably PAS positive.
IHC:+ FOR ACTH , β-LPH, endorphins, and POMC
EM: perinuclear cytoplasmic microfilament bundles are sparse or absent. Crooke
hyaline change is lacking in extratumoral ACTH cells.
Malignant transformation of Nelson adenomas accounts for a significant
proportion of pituitary carcinomas
TREATMENT-SURGERY.

65. CROOKE CELL ADENOMA
INCIDENCE:<1%
C/F-Hypercortisolism
HISTOMORPHOLOGY: GROSS- 25% micro/75% macro
MICROSCOPY:B -C, INVASION-85%
BLOOD HORMONES:-↑ACTH, β-LPH, endorphins, and POMC
IHC+ FOR ACTH, β-LPH, endorphins, and POMC
EM: Same as ACTH adenoma but with marked to massive accumulation of
macrofilaments

66. SILENT CORTICOTROPIC-
INCIDENCE-3%
C/F-Mass symptoms; hypopituitarism
DIAGNOSIS:
 BLOOD HORMONE LEVELS:↑ACTH, β-LPH, endorphins and POMC
 HISTOPATHOLOGY: GROSS-100% macro adenomas
MICROSCOPY-B-C
 IHC:+ACTH, β-LPH, endorphins, and POMC

67. EM:
Silent subtype 1
-Resembles densely or sparsely granulated Cushing adenoma
Silent subtype 2
Numerous RER, prominent Golgi bodies
150-300 nm, Irregular Drop-shaped; Sparsegranules:
Miscelleneous :No perinuclear and cytoplasmic microfilaments

68. Silent corticotroph adenoma type 2:small granules
with no hyalinisation

69. GONADOTROPIC ADENOMA
INCIDENCE-7%-15%
Tumors producing LH and FSH are relatively common and represent the majority of
nonfunctioning adenomas
Few are associated with MEN1
Most occur in older adults, with men being preferentially affected.
Elevation of serum LH and FSH levels is best seen in males because physiologic
elevation of gonadotropins is normal after menopause.
C/F:
1.Hypogonadism;
2.Functionally silent
3.Mass effects -neurologic and visual symptoms (72%), as well as hypopituitarism
(67%)

70. Hypothalomogonadal axis

71. DIAGNOSIS:% Radiographic or gross apparent invasiveness is noted in only 20%
to 30% of cases
BLOOD HORMONE LEVELS:↑↑ FSH and LH,(ONLY IN15%) rest are non
functional
LH, FSH LH, FSH, testosterone, estrogen Basal measurements –
-Basal LH and FSH should be increased in postmenopausal women
-Low testosterone levels in the setting of low LH and FSH indicate pituitary
insufficiency
-Free α subunit levels may be elevated in 10–15% of patients with Non functioning
tumors.
-In female patients, peri- or postmenopausal basal FSH concentrations are difficult
to distinguish from tumor derived FSH elevation..

72. Premenopausal women have cycling FSH levels, also preventing clear-cut
diagnostic distinction from tumor derived FSH.
In men, GnRH tumors may be diagnosed because of slightly ↑gonadotropins
(FSH > LH) in the setting of a pituitary mass.
In majority of pts with gonadotrope adenomas, TRH administration
stimulates LH β subunit secretion; this response is not seen in normal
individuals.
GnRH testing, however, is not helpful for making the diagnosis.
 For nonfunctioning & GnRH secreting tumors, the diagnosis usually rests on
immunohistochemical analyses of surgically resected tumor tissue,

73. GROSS: 5% micro/95% macro ( large macroadenomas with suprasellar extension)
LM: C-B
Adenoma cells are polygonal to elongated. Some are diffuse in pattern, but
others show perivascular pseudorosettes or even papillae.
Chromophobic or oncocytic,
contain only scant, peripherally situated, PAS-positive granules.

74. LM:Adenoma cells are polygonal to elongated. Some are diffuse in
pattern, but others show perivascular pseudorosettes or even papillae.

75. Treatment: Only approx.5% of gonadotropic adenomas require reoperation ..
Pituitary apoplexy is a recognized complication
.
IHC: Chromogranin staining is strong.
 MIB-1 labeling is typically low (<3%).
Steroidogenic factor 1 (SF1), the transcription factor associated with
gonadotrophs, is also demonstrable.
 Immunostains :+ FSH and/or LH and often for the α-subunit as well.
EM: Polar cells with process formation and small numbers of minute secretory
granules disposed beneath the plasmalemma.

76. Pituitary apoplexy-The sellar region in coronal sections shows a massive
hemorrhage within a macroadenoma.

77. Gonadotropic Adenoma:Honey coombing and vacuolisation of
golgi complex .

78. THYROTROPH CELL ADENOMA
Thyrotropic tumors - least common of the pituitary adenomas.( Incidence1%)
Majority occur in adults and affect females
TSH-producing adenomas are seen in the setting of MEN1 and Carney complex,
some as plurihormonal lesions .
Most arise in the setting of hyper- or hypothyroidism
A significant number cause elevated serum TSH levels in association with normal
T3&T4 levels, a condition termed “inappropriate TSH elevation”.
Administration of TRH does not further increase TSH levels, thus distinguishing
TSH adenoma from pituitary resistance to thyroid hormone

79. In the setting of hypothyroidism, combined TSH and PRL cell hyperplasia causes
pituitary enlargement that may mimic an adenoma
C/F:hypothyroidism or hyperthyroidism
DIAGNOSIS:
BLOOD HORMONE:↑↑ TSH
1.Basal thyroid function tests: T4, T3, TSH –
- Low free thyroid hormone levels in the setting of TSH levels that are not
appropriately increased indicate pituitary insufficiency
2.TRH test: 200–500 μg IV 0, 20, 60 min for TSH and PRL - TSH should
increase by >5 mU/L unless thyroid hormone levels are increased

80. HYPOTHALMO -THYROID AXIS

81. HPE: GROSS: Usually invasive macroadenomas (75%)
MICROSCOPIC:C-B ,majority of these adenomas are chromophobic tumors
showing only mild PAS positivity.
HISTOCHEMICAL STAINING: PAS; aldehyde fuchsin; aldehyde thionin
(A)Glycoprotein adenomas often contain spindle-shaped cells and they show
little or no PAS reactivity. (B) Immunoreaction for TSH varies in intensity

82. IHC :TSH , most are also immunoreactive for α-subunit.
EM:
Ultrastructurally, their cells resemble normal thyrotrophs, featuring
processes containing microtubules,
prominence of lysosomes,
sparse, minute secretory granules
TREATMENT: medical therapy and/or radiotherapy are often required

83. Thyrotroph cell adenoma:angular shape cell accentuated by
small secretary granules

84. PLURIHORMONAL ADENOMAS
INCIDENCE-10%
C/F:Usually acromegaly ± hyperprolactinemia; glycoprotein hormone production
rarely expressed
 BLOOD HORMONES:
Usually GH, PRL, and TSH, α-subunit; includes other unusual combinations
-Combined anterior pituitary test: GHRH(1 g/kg), CRH (1 μg/kg), GnRH (100 g),
TRH (200 μg) are given IV
- 0, 15, 30, 60, 90, 120 min for GH,ACTH, cortisol, LH, FSH, and TSH
-Combined or individual releasing hormone responses must be elevated in the
context of basal target gland hormone values and may not be uniformly diagnostic

85. GROSS:25% micro/75% macro , MICROSCOPY:C-A
INVASION:52%
IHC:Usually +/+/+ GH, PRL, and TSH, α-subunit

86. SILENT SUBTYPE 3
INCIDENCE-3%
C/F Mass effects; hyperprolactinemia or GH effects
 BLOOD -No specific hormone
GROSS:Usually macro
MICROSCOPY: C to mild A and show some degree of nuclear pleomorphism
and nucleolar prominence.
INVASION-Frequent
IHC:Scant to variable GH (10%), PRL (10%), or TSH; rare ACTH
EM: shows polar cells, Pleomorphic nuclei containing multiple spheridia.
Both RER & SER are abundant, whereas secretory granules are sparse and
small.

87. Silent corticotroph adenoma type 3:large cells with
nuclear pleomorphism,cytoplasm is packed with
SER,RER & prominent golgi bodies.

88. NULL CELL ADENOMAS
Incidence-20%
Two types-Non oncocytic & oncocytic
These tumors are relatively devoid of organelles and lack specific differentiation —
hence the term null cell adenoma.
Age- > 40 and come to clinical attention as a result of mass effects.
Majority of patients show laboratory evidence of hypopituitarism.
Prognosis is favorable, with a recurrence rate of approximately 10%

89. C/F: both present with Visual symptoms; hypopituitarism;
headaches
BLOOD HORMONES-None ± mild hyperprolactinemia as
a result of pituitary stalk compression
GROSS:5% micro/95% macro
Nononcocytic
Incidence-14%
LM-Chromophobic
Oncocytic
Incidence-6%
LM: Acidophilic

90. Null cell adenoma. (A) nononcocytic-chromophobic, (B) oncocytic as a result of
mitochondrial accumulation.

91. Null cell adenoma with poorly developed ER & golgi complex with
scant secretary granules

92. IHC-No reaction for hormones,but + for synaptophysin and chromogranin
HISTOCHEMICAL STAIN: PAS-VE
EM: contain only sparse, small, sub plasmalemmal secretory granules in
association with poorly developed organelles
INVASION-42%

93. Pituitary oncocytoma with abundance of mitochondria

94. PITUITARY CARCINOMA
Pituitary carcinomas are rare; only approximately 100 cases have been
reported
Most occur in gradual transition from typical or atypical, often invasive
macroadenomas.
Latency period is generally 5 to 10 years,few arise de novo.
Only adults have been affected.

95.  Cytologic atypia and a brisk mitotic index are predictive of aggressive
behavior, some show neither.
Ultrastructural studies of pituitary carcinomas often show some loss of
differentiation
pituitary carcinoma” is predicated on the finding of one or more of the
following:
(a) Discontinuous spread within the cerebrospinal space
(a) Extracranial metastases, typically to liver, bone, lymph node, or lung, by
way of the bloodstream or lymphatics
(c) Gross brain invasion ,LM or cytologic features alone are of little use in
establishing the diagnosis of carcinoma

96. PITUITARY ADENOMA WITH NEURONAL METAPLASIA
(GANGLIOCYTOMA)
Neurons are occasionally found within the substance of pituitary adenomas
Most are sparsely granulated GH-producing adenomas associated with
acromegaly.
The neurons in such tumors often produce GHRH ,Similarly, CRH-producing
neurons have been observed with Cushing disease.
The light microscopic, ultrastructural, and immunocytologic features of the neurons
vary in terms of cell size, nuclear number, and content of Nissl substance
Occasional keratin staining of the neurons also supports the metaplasia concept.

97. Gangliocytoma of the pituitary-composed of hypothalamic-type neurons situated
within the substance of a GH cell adenoma. Immunostains show that the neurons
contain growth hormone-releasing hormone.