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Ackerman Atlas(chaptr44)

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Pituitary Gland

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 Figure 44.1 Fetal pituitary gland at 12 weeks' intrauterine gestational age shows TTF1 immunoreactive nuclei already identifiable in the posterior gland (at left) but not in the anterior gland (at right)

 

Figure 44.2 Adult posterior pituitary gland with nuclear TTF1 immuno- reactivity; TTF1 IHC does not distinguish between normal posterior gland and TTF1 IHC(+) sellar region tumors, such as pituicytoma, spindle cell oncocytoma, and granular cell tumor of the neurohypophysis

 

 Figure 44.3 Fetal pituitary gland at 22 weeks' intrauterine gestation shows clear distinction between fibrillary posterior (upper right) and highly vascular epithelial anterior (lower left) portions of the gland

 

Figure 44.4 Fetal pituitary gland at 22 weeks' intrauterine gestation already shows immunoreactivity for anterior pituitary hormones, with growth hormone from the lateral wings illustrated here

 

 Figure 44.5 Sagittal magnetic resonance imaging (MRI) scan shows normal adult anterior and posterior pituitary and sellar region anatomy. The posterior pituitary "bright spot" is a normal MRI finding, referring to the intrinsically high T1 signal in the posterior pituitary attributed to the storage of vasopressin

 

 

 Figure 44.6 Diffuse immunoreactivity with PIT1 transcription factor identifies shared lineage in a large family of adenoma types: sparsely granulated prolactinomas, densely granulated prolactinomas, acidophil stem cell adenomas, densely granulated growth hormone adenomas, sparsely granulated growth hormone adenomas, mixed GH-PRL adeno- mas, thyrotroph adenomas, and plurihormonal PIT1-positive adenomas, formerly known as "silent type 3 adenomas."

 

Figure 44.7 Steroidogenic factor-1 (SF1) is the transcription factor associated with gonadotroph adenomas, and the presence of nuclear IHC is the defining feature of this adenoma type, even if follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH) IHC are not present. Null cell adenomas, in contrast, are SF1 negative, as well as negative for PIT1 and adrenocorticotropic hormone (ACTH)

 

 

Figure 44.8 Normal anterior pituitary gland shows an assortment of cell types on H&E arranged in clusters known as acini; the different cell types vary in numbers between the lateral wings, where more GH and PRL cells are located, versus the median wedge where more ACTH cells are found

 

Figure 44.9 Reticulin stain better allows for appreciation of the normal acinar pattern of the anterior pituitary gland than does H&E staining

 

Figure 44.10 All pituitary adenomas, regardless of cell type, are diffusely mmunoreactive for synaptophysin; blood vessels show lack of mmunostaining in this image

 

Figure 44.11 Normal posterior gland contains abundant axons, highlighted here by neurofilament immunohistochemistry; this can occasionally be very helpful in distinguishing normal posterior gland from spindle cell tumors such as schwannoma or meningioma that occasionally frequent the sellar region

 

Figure 44.12 Pituitary blastoma is a very rare infantile pituitary tumor that is associated with DICER1 mutation and is almost inevitably IHC(+) for ACTH, as in this example

 

 Figure 44.13 Incidental pituitary adenomas are a frequent finding not only on premortem neuroimaging studies but at the time of autopsy; this one was a prolactinoma

 

Figure 44.14 Pituitary adenomas more than 1 cm in greatest dimension are termed macroadenomas; compare with the sagittal MRI shown of normal gland in Fig. 44.5

 

Figure 44.15 Giant pituitary adenomas, defined as greater than 4 cm, sometimes extend into the nasopharyngeal space, mimicking a naso- pharyngeal carcinoma

 

Figure 44.16 The protocol for examination of pituitary tumor specimens suggests that bony invasion seen microscopically should be "included in the protocol when known." This sparsely granulated growth hormone adenoma, a subtype known to be aggressive, encompasses bone spicules from the invaded sellar floor. However, even "benign," less aggressive subtypes may invade the sella

 

Figure 44.17 The protocol for examination of pituitary tumor specimens suggests that nasal sinus invasion seen microscopically should be "included in the protocol when known." Note the adenoma (at right) immediately adjacent to respiratory mucosa of the sinus (at extreme left)

 

Figure 44.18 Dural invasion is far more commonly identified microscopi- cally when the surgeon specifically submits a specimen of dura for examination; note the hypercellular adenoma (upper right) in contrast to the hypocellular dura (lower left)

 

Figure 44.19 Touch preparations at the time of intraoperative consultation show abundant exfoliation of relatively monomorphic adenoma cells onto the slide, with the volume of cells shed roughly proportional to the size of the adenoma tissue fragment. Note the mitotic figure (central) in this example, although mitoses are not often identified. Indeed, if several mitoses are found on touch imprint, suspicion for an elevated MIB-1 proliferation index in the adenoma should be raised

 

Figure 44.20 Reticulin stain is the single best histochemical stain for confidently identifying adenoma, although there may be some variation in the degree of acinar disruption/dissolution. In this microadenoma, note the disruption of the reticulin pattern (upper right) as compared to the sharp demarcation from intact anterior gland (lower left)

 

Figure 44.21 Reticulin stain in a macroadenoma usually shows preserva- tion of reticulin fibers only around vascular structures

 

 

Figure 44.22 A variation of acinar disruption causing a macronodular pattern can be seen in some macroadenomas, especially gonadotroph adenomas; this is still an abnormal pattern (compare with Fig. 44.9)

 

 

Figure 44.23 Gonadotroph adenomas manifest several different archi- tectural patterns, including the sheet-like arrangement of cells shown here

 

Figure 44.24 Gonadotroph adenomas may show a macronodular pattern; compare this image with the reticulin stain illustrating this pattern in Fig. 44.22

 

Figure 44.25 Gonadotroph adenomas occasionally have clear cytoplasm. This example has some degree of nuclear pleomorphism; all adenomas can contain occasional cells with nuclear enlargement and hyperchro- matism, and this is of no prognostic importance

 

Figure 44.26 Gonadotroph adenomas frequently contain subpopulations of cells with abundant oncocytic cytoplasm (upper left) and cells with scant chromophobic cytoplasm (lower right). This dichotomous population should not be misinterpreted as a "double" or "dual" adenoma since the same transcription factor (SF1) and/or FSH/LH immunostaining is seen in both components

 

Figure 44.27 Gonadotroph adenoma may mimic ependymoma with perivascular structuring of adenoma cells around blood vessels

 

Figure 44.28 Gonadotroph adenoma often shows discohesion of cells, leaving the preserved cells clustered around blood vessels and forming pseudopapillary patterns

 

Figure 44.29 Gonadotroph adenomas may show patchy FSH positivity but never diffuse staining as in prolactinomas or densely granulated GH or ACTH adenomas

 

Figure 44.30 Gonadotroph adenoma shows patchy LH IHC(+), but this is usually in a smaller subpopulation of the adenoma cells than is FSH IHC(+), or may not be present at all

 

 Figure 44.31 Hormone-negative adenomas often show a perivascular "pseudorosette" like pattern identical to that seen in gonadotroph adenomas

 

Figure 44.32 Hormone-negative adenomas may be composed of a very monomorphic population of cells, punctuated only by a few mucin-filled microcysts

 

Figure 44.33 Densely granulated growth hormone adenomas show perinuclear keratin that is present throughout the cytoplasm with CAM5.2 immunostaining

 

Figure 44.34 Sparsely granulated GH adenomas, by definition, have dot-like cytoplasmic round fibrous bodies in greater than 70% of adenoma cells with CAM5.2 immunostaining

 

Figure 44.35 Intermediate/mixed/transitional growth hormone adenomas show a predominance of perinuclear CAM5.2 staining but have occasional admixed fibrous bodies or keratin accumulations that are not easily categorized as either perinuclear or fibrous bodies. These adenomas behave like densely granulated growth hormone adenomas, especially in terms of response to somatostatin analogues, and should not be misconstrued as sparsely granulated GH adenomas

 

Figure 44.36 This mixed GH-PRL adenoma clearly shows two admixed populations of chromophobic and eosinophilic cells on H&E

 

 Figure 44.37 Mixed GH-PRL adenomas present with acromegaly, and a significant percentage of the adenoma cells stain with GH

 

Figure 44.38 Although mixed GH-PRL adenomas present with acro- megaly, they are often associated with hyperprolactinemia as well and as shown here contain a higher percentage of PRL+ cells than densely granulated GH adenomas, which should only contain occasional cells that are immunoreactive for PRL

 

Figure 44.39 Sparsely granulated prolactinomas constitute the overwhelm- ing majority of prolactinomas, and usually feature a sheet-like growth pattern; note the relative prominence of nucleoli (compare with Fig. 44.32)

 

Figure 44.40 Sparsely granulated prolactinomas show PRL positivity in an arc-like cytoplasmic pattern, the so-called Golgi pattern. In contrast, the very rare densely granulated PRL positive adenomas show PRL immunoreactivity throughout the cytoplasm

 

 Figure 44.41 Sparsely granulated prolactinomas occasionally show stromal hyalinization and microcalcifications, both of which are pictured here

 

Figure 44.42 Atypical adenomas are defined by an elevated MIB-1 labeling index, although this does not correlate perfectly with adenoma subtype. Indeed, even the well-accepted "aggressive" adenoma subtypes, such as sparsely granulated GH, acidophil stem cell, and silent ACTH adenoma, do not invariably show elevated indices. In some studies, the most common subtype to show elevated MIB-1 is sparsely granulated prolactinoma, as illustrated here. Acidophil stem cell adenoma was excluded in this case by clinical and EM features

 

Figure 44.43 Acidophil stem cell adenoma usually presents as a large tumor, with relatively mild hyperprolactinemia for tumor size in comparison to sparsely granulated prolactinomas. Acidophil stem cell adenomas cannot be confidently diagnosed without electron microscopic examination, however. One clue in some cases is the presence of large clear vacuoles corresponding to the giant mitochondria seen on EM

 

Figure 44.44 Acidophil stem cell adenomas usually require EM for confident diagnosis, but antimitochondrial antibodies are being investigated as possible surrogate IHC markers; note how the immunoreactivity rims the vacuole, indicating that the vacuole is indeed a mitochondrion

 

Figure 44.45 This densely granulated corticotroph adenoma is composed of sheets of large cells with basophilic cytoplasm

 

Figure 44.46 Densely granulated corticotroph adenomas show diffuse ACTH immunoreactivity throughout the tumor. Unlike sparsely granulated prolactinomas where adenoma size parallels the serum level of prolactin, minute ACTH adenomas, even millimeters in size, may cause Cushing disease and significantly elevated serum levels

 

Figure 44.47 Sparsely granulated corticotroph adenomas are usually chromophobic

 

Figure 44.48 Sparsely granulated corticotroph adenomas show focal or patchy ACTH positivity

 

Figure 44.49 Crooke cells in adjacent nontumorous anterior pituitary gland testify to the presence of hypercortisolism, and this change should be sought in any included anterior gland from a corticotroph adenoma resection specimen. Rings of keratin push the ACTH-positive granules close to the nucleus, as well as to submembrane sites

 

Figure 44.50 Pituitary apoplexy can be seen in several types of adenomas, usually macroadenomas, and may either manifest as bland necrosis, as illustrated here in an adenoma that was present within clival bone, or as acute/subacute hemorrhage

 

Figure 44.51 Rathke cleft cyst contains variably dense colloid-like proteinaceous contents, usually visible as amorphous eosinophilic material (left). The lining epithelium is often not sent to the pathologist, but, when received, may be columnar ciliated epithelium (as seen here), low cuboidal, or even show squamous metaplasia

 

Figure 44.52 Adamantinomatous craniopharyngioma is characterized by peripherally palisaded nuclei, clusters of eosinophilic cells devoid of nuclear staining, so-called ghost cells (also known as wet keratin), focal calcification, and often, surrounding piloid gliosis with Rosenthal fiber formation (upper right and at left)

 

Figure 44.53 Adamantinomatous craniopharyngioma has an underlying mutation in B-catenin and translocation of the protein to the nucleus, which can thus be documented by immunohistochemistry. It should be noted that nuclear ẞ-catenin staining is never seen in all tumor cells, but instead concentrates in cells immediately adjacent to wet keratin or within whorled squamous nests (seen in the plane of section at lower right)

 

Figure 44.54 Papillary craniopharyngioma lacks the prominent peripheral palisaded nuclei, wet keratin, and calcification of the adamantinomatous variety; note the hyalinized, collagenous whorl-like structures that should not be mistaken for wet keratin

 

 

Figure 44.55 Papillary, squamous craniopharyngiomas are composed of benign nonkeratinizing epithelium devoid of a keratohyaline layer, unlike epidermoid cysts. Unlike adamantinomatous craniopharyngioma, papillary craniopharyngioma manifests mutation in BRAF V600E, which is paralleled by BRAF VE1 immunoreactivity, as shown here with a red chromogen

 

Figure 44.56 Pituicytoma is a spindle cell sellar region mass easily mistaken on light microscopy for meningioma, schwannoma, or even normal posterior pituitary gland

 

Figure 44.57 Pituicytoma, like the related spindle cell oncocytoma and granular cell tumor of infundibulum, shows nuclear reactivity for TTF1, negating consideration of meningioma, schwannoma, or even pituitary adenoma. The cell density and architectural pattern distinguishes it from TTF1+ normal posterior gland

 

Figure 44.58 Spindle cell oncocytoma is composed of cells with plumper, more epithelioid-appearing eosinophilic cytoplasm but does have overlapping features with pituicytoma, most notably the shared TTF1 immunoreactivity

 

Figure 44.59 Spindle cell oncocytoma is characterized by more abundant cytoplasmic mitochondria than are present in pituicytoma, as seen here on anti-mitochondrial immunohistochemistry

 

Figure 44.60 Metastases to the pituitary gland usually obliterate or compress the gland, but occasionally the tumor and residual anterior pituitary cells are intimately admixed; compare the metastatic breast carcinoma at left with the normal anterior pituitary gland showing all three cell types (chromophobes, basophils, eosinophils) at right

Figure 44.61 Metastatic breast carcinoma to the pituitary gland has so intimately infiltrated the anterior pituitary that acini are not totally destroyed; prolactin-immunoreactive residual normal anterior pituitary cells envelop nests of the metastatic tumor

 

Figure 44.62 In this case the metastatic breast carcinoma shows strong diffuse nuclear immunoreactivity for estrogen receptor. Note, however, that the residual normal anterior pituitary gland, at lower right, also contains a few scattered, smaller-sized nuclei that are also ER positive. These are either gonadotrophs or lactotrophs