1. Adrenal lesion in Conn syndrome

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

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

4. 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

5. 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

6. Another case

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

9. Pleomorphism and nuclear atypia maybe present in these benign tumors.

10. 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.

11. Adrenal Cushing Syndrome

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

14. Surgical Specimen: Adrenalectomy

15. Cushing syndrome, clinical manifestation
Trunkal obesity
Striae
Recovery

16. Formation of nerve ganglion

18. H&E

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

20. Adrenocortical Carcinoma

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

22. 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

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

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

25. 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

26. 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.

27. 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.

28. 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.

29. 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

30. 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

31. 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’.

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

33. 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

34. 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.

35. 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 .

36. 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

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

38. 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

39. 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

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

41. Multiple Endocrine Neoplasia syndromes (MEN)

42. Hyperparathyroidism Pathology