Pathology of the human pituitary adenomas

Abstract

This article describes pertinent aspects of histochemical and molecular changes of the human pituitary adenomas. The article outlines individual tumor groups with general, specific and molecular findings. The discussion further extends to the unusual adenomas or carcinomas. The description in this article are pertinent not only for the practicing pathologists who are in the position of making proper diagnosis, but also for the pituitary research scientists who engage in solving basic problems in pituitary neoplasms by histochemistry and molecular biology.

Fig. 1

Pathological diagnosis in pituitary adenomas. A total of 382 pituitary adenomas are classified with functional classifications using histology, IHC, ultrastructural features as well as biochemical, imaging and surgical findings in surgical resection at Nippon Medical School since 1977. The tumor cells in FNA are positive for gonadotropin SU, and belonging to gonadotropin producing adenoma

Fig. 2

A pie chart of the ratio of pituitary macro and micro adenomas. Pituitary adenomas are ordinary macroadenomas except for ACTHomas

Fig. 3

Human pituitary cell linage. Pituitary-specific or related transcription factors involved in the development of pituitary gland. αSU is expressed in some of the normal human GH-producing cells and some cases of GH-producing adenomas as it occurs in mice

Fig. 4

GH producing (cell) adenoma (GHoma). The tumor cells of hematoxylin eosin (H&E) staining (a). In IHC, it shows many GH positive tumor cells (b), frequently cells are also positive for PRL (c) and αSU (d). The IHC of pituitary-specific transcription factor 1 (Pit-1), which regulate the functional differentiation of GH–PRL–TSH cell lineage (e). In electron microscopy, many GHoma are type of densely granulated cells, which contain many dense cored numerous secretory granules (f). SSTR2a is immunostained in cell membrane (g), which provides important information for SSAs therapy

Fig. 5

The IHC of GH of densely and sparsely granulated adenomas. Densely granulated adenoma shows strong and diffuse cytoplasmic immunoreactivity for GH (a). Sparsely granulated adenomas show weak GH immunostaining (b)

Fig. 6

The IHC of CAM 5.2 keratin (CK8). In some GHomas, the tumor cells shows globules of keratin, which are called as fibrous bodies, by IHC (a). b Shows magnified image of dot type fibrous bodies. In granulated adenomas, keratin is immunostained in cytoplasm (c). In electron microscopy, fibrous bodies shows smooth endoplasmic reticulum located in the Golgi region (d)

Fig. 7

PRL producing (cell) adenoma (PRLoma). The tumor cells of hematoxylin eosin (H&E) staining (a) and IHC of PRL, which shows condense in the Golgi regions near the nuclei (b). In electron microscopy, prominent Golgi saccules and a few small NSGs are seen (c). d shows the extrusion of secretory granules, so called “misplaces exocytosis”

Fig. 8

Crooke cell adenoma. The Crooke cell adenoma of hematoxylin eosin (H&E) staining, which is characterized by densely eosinophilic and hyaline cytoplasm (a). The IHC of ACTH (b). c Shows the image of CAM 5.2 (keratin) immunostaining. Electron microscopy showed the accumulation of massive intermediate filaments (asterisk) (d)

Fig. 9

TSH producing (cell) adenoma (TSHoma). The tumor cell of hematoxylin eosin (H&E) staining (a). It is clearly showed by Heidenhain’s azan stain, the stromal fibrosis in tumors (b)

Fig. 10

IHC of TSH (TSHoma). It shows many TSH positive tumor cells (a), and multihormonal with the concominant production of PRL (b) and GH (c). For transcription factors, Pit-1 (d) and GATA-2 (e) are positive and sometimes ER (f) is positive

Fig. 11

FSH producing (cell) adenoma (FSHoma). The tumor cells were organized into pseudorosette patterns (a). About 40% of FSHomas are immunopositive for αSU (b), FSHβSU (c) and SF-1 (d). In contrast, LHβSU immunoreactivity is rare

Fig. 12

Gonadotropin producing (cell) adenoma (Gn-oma). Mid-sagittal (a) and coronal (b) MRI image. The tumor cells present macroadenoma type and no evidence of bioactivities of hormone. αSU (c, d; blue), FSHβSU (c; brown) and LHβSU (d; brown) are localized in different tumor cells

Fig. 13

H&E staining of the tumor cells (a). Neuroendocrine marker SNAP25 (b) and pituitary hormone FSHβ (c) and ACTH (d) are detected. e Electron microscopy shows dense cored secretory granules

Fig. 14

H&E staining of the tumor cells (a). IHC of GH (b) and GHRH (c). It is suggested that GHRH stimulates the hyperplastic GH cells