Adrenal lesion in Conn syndrome

Adrenalectomy in a case of Conn syndrome due to a cortical adenoma

Conn syndrome due to a cortical adenoma is frequently detected among hypertension in the young.

Tumor shows circumscribed borders, thin fibrous encapsulation maybe identified. The rest of the cortical tissue shows atrophic change, both from suppression and from pressure effect. Lymphoid cells

Tumor cells show polygonal shape and lipid vacuoles (seen as foamy cytoplasm) with arrangement in cords or trabeculae, features seen in normal adrenal cortex. H&E

Another case

Another case with tumor protruding on one side of the gland Adrenal vein Normal part of the gland appears atrophic with rather thick capsule

Pleomorphism and nuclear atypia maybe present in these benign tumors.

This patient had a very small cortical adenoma Conn syndrome This patient had a very small cortical adenoma that produced Conn syndrome A case of Conn syndrome presenting with hypertension and being treated as a case of essential hypertension Histologic features of cortisol producing tumor and aldosterone tumor are indistinguishable.

Adrenal Cushing Syndrome

Hypercortisolism (Cushing syndrome) causes & pathogenesis (Cushing Disease)

Surgical Specimen: Adrenalectomy

Cushing syndrome, clinical manifestation Trunkal obesity Striae Recovery

Formation of nerve ganglion

H&E

Atrophic change of adrenocortical tissue in both adrenal glands because low ACTH level

Adrenocortical Carcinoma

A rare case of functional adrenocortical carcinoma with virilizing effects in a female patient

Histopathologic features are that of high-grade maligjnancy Notice the marked pleomorphism and cytologic / nuclear atypia among the tumor cells Vascular invasion is readily identified

Also a rare case of functional adrenocortical carcinoma presenting with Cushing syndrome

Adrenocortical Tumors Adrenocortical Carcinoma, non-functioning Adenoma with Conn syndrome

Adrenocortical Tumors benign malignant Majority of cortical adenomas are nonfunctional and not clinically detected. Functional & Nonfunctional tumors have the same morphologic features Nuclear pleomorphism may be present Adrenocortical carcinoma is rare type neoplasm In functional cases (rare), more commonly associated hyperadrenalism with virilism Hightly malignant, usually large when discovered

Paraganglion system: What is the paraganglia? Small groups of cells formed behind the peritoneum (retroperitoneum), in the connective tissue capsule of the suprarenal gland, in the thoracic / abdominal sympathetic chains, in the urogenital organs, in the epicardium, near and around the kidneys, and elsewhere. Function: Probably involved in the production of adrenaline / noradrenaline and acetylcholine. The substances are secreted in the fetus to help maintain the blood pressure. After birth, the adrenal medulla and the autonomic nervous system take over this function Several paraganglia regress when the adrenal medulla becomes functional after birth, e.g., the aortic chromaffin body called ‘organ of Zuckerkandl’ located near the origin of the inferior mesenteric artery The persistent parts are usually fragmented, and the resulting paraganglion cells found in contact with sympathetic ganglia or even some blood vessels. Some paraganglia cells, located near the vagus nerve, the glomus jugulare, are found to secrete acetylcholine. These cells do not show chromaffin reaction, as those of the adrenaline-producing paraganglia such as adrenal medulla, sometimes called non-chromaffin paraganglia. Several paraganglia function as chemoreceptor and baroreceptor, such as carotid body, carotid sinus and aortic body.

Clinical Significance Tumors of paraganglia are usually highly vascularized. Size of the tumor may not correlated with severity of symptoms. Paraneoplastic syndromes due to secretion of active substances. May present unexpected symptoms due to sudden release of secretion upon manipulation.

Histopathology of Paragangioma Cytoplasmic granules may be seen due to richness in mitochondria and/or secretory granules. Chromaffin-reaction is useful in detection of chromaffin paraganglioma (phaeochromocytoma) . Highly vascularized. Tumor cells arrange in groups or cluster surrounded by vascular structures, so called ‘organoid feature’. Pleomorphism and atypia among tumor cells do not determined malignant nature.

Adrenal medulla tumor: Phaeochromocytoma 1/10 % of hypertensive patient having underlying phaeochromocytoma 10% of phaeochromocytoma found extraadrenal 10% familial (autosomal dominant) 10% bilateral 10% malignant

Morphology of Phaeochromocytoma Yellow-tan tumor substance Incubation of fresh tumor with dichromate turns tumor to dark brown (phaeo=brown) Polygonal tumor cells having lobular arrangement or cell ball (zellballen) with highly vascularized stroma (organoid pattern) Cytologic atypia among tumor cells not indicating malignant nature

Adrenal medulla: Phaeochromocytoma The tumor would become much darker brown color after leaving in fixative for a period of time due to oxidation and polymerization of catecholamine similar to that occur in chromaffin reaction. Chromaffin reaction: After fixation in chromate-containing solution, tumor tissue appeared ‘mahogany-brown’.

Phaeochromocytoma Highly vascularized tumor with organoid feature Rich cytoplasmic granules, the chromaffin granules and mitochondria Cytologic atypia among tumor cells not indicating malignant nature

Zenker fixed tissue: H&Ex128 Formalin fixed tissue: H&Ex128 -Due to richness in mitochondria and secretory granules in the tumor cells, the cytoplasm appears granular -Note the brownish hue in the Zenker fixed tissue from chromaffin reaction among the cytoplasmic granules -Variation in size and shape of tumor cells and nuclear pleomorphism are not sign of malignancy in this tumor

Chromaffin granule demonstration by transmitted electron microscope Chromate treatment H & E (chromaffin reaction) Cherry-red granules in Mallory stain T E M: Membrane-bound-electron-dense secretory granules in tumor cells.

Adrenalectomy specimen: Total weight of 102 gm, showing bulging tumor mass having smoothsurface and showing no adhesion to surrounding structures Part of adrenocortical tissue seen displaced by the bulging tumor to one side of the specimen .

Fresh specimen: -Cut section shows tumor mass having thin capsule Fresh specimen: -Cut section shows tumor mass having thin capsule. The tumor occupied the whole adrenal gland substance, thus no part of normal gland identifiable. -Tumor tissue shows reddish-brown color with hemorrhagic foci . -A central scarred area (arrow) is also present. capsule

Adrenal vein Adrenal cortex Formalin fixed: H&E, x8

Adrenal cortex with pressure effect from the expanding tumor Zenker fixed: H&E, x12.8 Tumor cells arrange in distinctive cell balls, so called ‘Zellballen’ or organoid structure, among highly vascularized stroma

Comparing staining characters in Zenker fixed and formalin fixed tissue, both with H&E routine stain Note the brown color tint in Zenker fixed tissue due to the chromaffin reaction Zenker’s fixative contains mercuric chloride (HgCl2) and potassium dichromate (K2Cr2O7). The chemical causes chromaffin reaction by oxidative process and polymerization of catecholamines that make brown color substance

Multiple Endocrine Neoplasia syndromes (MEN) A group of familial disorders with hyperplasia or/and neoplasia of several endocrine organs Inherited as autosomal dominant traits

Multiple Endocrine Neoplasia syndromes (MEN)

Hyperparathyroidism Pathology