ENDOCRINE PATHOLOGY

Published on 07/03/2015 by admin

Filed under Pathology

Last modified 22/04/2025

Print this page

This article have been viewed 2022 times

[level-membership-for-pathology-category]

CHAPTER 4 ENDOCRINE PATHOLOGY

CONGENITAL ADRENAL HYPERPLASIA

• Most 21-hydroxylase deficiency

present with virilization

• Diffuse bilateral cortical enlargement

esp zone reticularis

ADRENAL ‘CYSTS’

• Pseudocysts due to previous hemorrhage

• Endothelial lined vascular / lymphatic cyst

• Cystic degeneration of adrenal tumor including NTs

• True epithelial lined cysts

Beckwith–Wiedemann syndrome

• V rare ectopic bronchogenic adrenal cysts

HETEROTOPIC TISSUE IN ADRENALS

• Well reported including:

ADRENAL CORTICAL ADENOMA / CARCINOMA

Epidemiology

• Mainly older adults

• Well reported smaller peak in frequency in early childhood:

most are sporadic

may be associated with Li–Fraumeni or Beckwith–Wiedemann syndrome

• Children have overall better prognosis than adults

Histopathological features (Figs 4.1–4.7)

• Sheets and trabeculae of cells morphologically resembling normal adrenal cortex

clear and eosinophilic cytoplasm

– variable nuclear atypia and mitotic rate

• Main features suggesting malignant behavior (carcinoma vs adenoma):

capsular invasion

vascular invasion

greater mitotic rate

Fig. 4.1

Figs 4.1–4.2 Photographs of a resected adrenocortical carcinoma, measuring more than 10cm in maximum extent, the cut surface showing a solid tan yellow appearance with areas of necrosis.

Fig. 4.3

Fig. 4.4

Fig. 4.5

Fig. 4.6

Figs 4.3–4.7 Photomicrographs of a case of adrenocortical carcinoma in a child, demonstrating focal necrosis and marked nuclear pleomorphism. There was also capsular and vascular invasion and local recurrence appeared soon after surgery.

Immunohistochemical staining

• Alpha inhibin+

• Chromogranin negative (cf medullary tumors)

• May be only weakly positive for cytokeratin and EMA

• CEA negative

Differential diagnoses and pitfalls

• Smaller lesions difficult to predict clinical behavior from histological features

• May be related to germ-line point mutation of p53 even with no positive family history, acting in a tissue-specific manner (Ribeiro et al 2001)

PHAEOCHROMOCYTOMA

• Tumor of chromaffin cells of adrenal medulla

paraganglioma if affecting other sites

• Benign (90%)

• Malignant (10%: strictly defined by metastases)

Epidemiology

• Mainly sporadic

• >10% associated with NF-1, MEN2, VHL and/or familial cases

these more likely to present at younger age

Genetics

• Many abnormalities reported including RET defects but currently non-diagnostic

Clinical features

• Mass effect

• Catecholamine secretion effect

especially episodic hypertension

Histopathological features (Figs 4.8–4.10)

• Solid tumor with areas of hemorrhage / necrosis

• Nested architecture (zellballen) with surrounding sustentacular cells

uniform polygonal cell (sometimes spindled)

granular cytoplasm

variable nuclear pleomorphism

• Scattered melanin containing cells and ganglion cells may be present

Fig. 4.8

Fig. 4.9

Figs 4.8–4.10 Photomicrographs of a case of phaeochromocytoma, demonstrating a solid tumor with nested architecture (zellballen) of uniform polygonal cells with surrounding sustentacular cells, and variable nuclear pleomorphism.

Immunohistochemical staining

• S100+ sustentacular cells around nests

Differential diagnoses and pitfalls

• Some phaeochromocytomas may resemble adrenal cortical tumors on routine light microscopy

immunostaining and additional investigations may be required for definitive diagnosis

• Composite phaechromocytoma also has features of ganglioneuroma or other neuroblastic or nerve sheath tumor

usually affects adults

relatively increased frequency in NF1 / MEN2

• Compared to sporadic cases, in MEN 2, phaeochromocytomas:

may be preceded by diffuse medullary adrenal hyperplasia

– nodules <1cm diameter

more commonly bilateral and multiple

histologically identical

• Familial paraganglioma-phaeochromocytoma syndromes due to mutations in SDHB, SDHV and SDHD are also now recognized (Astuti et al 2001, Cascon et al 2002)

may present with tumors in childhood or adolescence

histologically similar to sporadic cases but more commonly

– multicentric

• Even apparently isolated familial phaeochromocytoma may be associated with germline VHL gene mutations (Crossey et al 1995, Frenzel et al 2001)

Extra-adrenal paraganglioma

• Similar histological features to phaechromocytoma but occurring at a wide range of other sites of paraganglia

• Usually adults

up to 50% familial

• Less clinical manifestations of increased catecholamines

• Mass effects

PREDISPOSING CONDITIONS ASSOCIATED WITH PHAEOCHROMOCYTOMA AND OTHER ENDOCRINE TUMORS

MULTIPLE ENDOCRINE NEOPLASIA TYPE 2 (MEN2)

• Autosomal dominant activating germline mutations of RET gene 10q11.2

specific codon mutations within RET correlate with disease phenotype and severity (Lakhani et al 2007)

• Three clinical syndromes:

familial medullary thyroid carcinoma (FMTC)

MEN2a (MTC, phaeochromocytoma, hyperparathyroidism)

MEN2b (MTC, phaeochromocytoma, neuromas, ganglioneuromatosis)

• Compared to sporadic cases, in MEN 2, phaeochromocytomas:

may be preceded by diffuse medullary adrenal hyperplasia

– nodules <1cm diameter

more commonly bilateral and multiple

histologically identical

• Parathyroid hyperplasia

all glands enlarged and hypercellular

variation in size

mainly cytologically bland chief cells

histologically identical to sporadic cases

• Rarely MEN2 is also associated with Hirschsprung’s disease

• In view of risk of medullary carcinoma of thyroid, prophylactic thyroidectomy is performed in childhood:

<6 years in MEN2a

<2 years in MEN2b

• Also screening for phaechromocytoma from age 6

HYPERPARATHYROIDISM–JAW TUMOR SYNDROME

• Hyperparathyroidism in late adolescence / early adulthood

due to parathyroid adenomas / carcinomas

• In association with ossifying fibroma of the maxilla / mandible and renal cysts and tumors (including Wilms’ tumor)

• Autosomal dominant

NEUROFIBROMATOSIS (NF) TYPE 1

• Around 1 in 3000

• Autosomal dominant mutations in NF1 17q11.2

many lesions present at birth or early childhood

• Family history NF1

• Other less common features (mainly affect adults):

carcinoid tumor

phaeochromocytoma

renal artery stenosis

Fig. 4.11

Fig. 4.12

Figs 4.11–4.13 Photomicrographs of a case of plexiform and diffuse neurofibroma in a child with NF1, demonstrating expanded nerve trunks and surrounding diffuse proliferation of bland tapered spindle cells.

Astuti D, Douglas F, Lennard TW, et al. Germline SDHD mutation in familial phaeochromocytoma. Lancet. 2001;357:1181-1182.

Cascon A, Ruiz-Llorente S, Cebrian A, et al. Identification of novel SDHD mutations in patients with phaeochromocytoma and/or paraganglioma. Eur J Hum Genet. 2002;10:457-461.

Crossey PA, Eng C, Ginalska-Malinowska M, et al. Molecular genetic diagnosis of von Hippel–Lindau disease in familial phaeochromocytoma. J Med Genet. 1995;32(11):885-886.

Frenzel S, Apel TW, Heidemann PH, Zerres K, Neumann HP, Dörr HG. Phaeochromocytoma associated with a de novo VHL mutation as form fruste of von Hippel–Lindau disease. Eur J Pediatr. 2001;160:421-424.

Lakhani VT, You YN, Wells SA. The multiple endocrine neoplasia syndromes. Annu Rev Med. 2007;58:253-265.

Ribeiro RC, Sandrini F, Figueiredo B, et al. An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma. Proc Natl Acad Sci USA. 2001;98:9330-9335.

[/level-membership-for-pathology-category][not-level-membership-for-pathology-category]

CHAPTER 4 ENDOCRINE PATHOLOGY

CONGENITAL ADRENAL HYPERPLASIA

• Most 21-hydroxylase deficiency

present with virilization

• Diffuse bilateral cortical enlargement

esp zone reticularis

ADRENAL ‘CYSTS’

• Pseudocysts due to previous hemorrhage

• Endothelial lined vascular / lymphatic cyst

• Cystic degeneration of adrenal tumor including NTs

• True epithelial lined cysts

Beckwith–Wiedemann syndrome

• V rare ectopic bronchogenic adrenal cysts

HETEROTOPIC TISSUE IN ADRENALS

• Well reported including:

ADRENAL CORTICAL ADENOMA / CARCINOMA

Epidemiology

• Mainly older adults

• Well reported smaller peak in frequency in early childhood:

most are sporadic

may be associated with Li–Fraumeni or Beckwith–Wiedemann syndrome

• Children have overall better prognosis than adults

Histopathological features (Figs 4.1–4.7)

• Sheets and trabeculae of cells morphologically resembling normal adrenal cortex

clear and eosinophilic cytoplasm

– variable nuclear atypia and mitotic rate

• Main features suggesting malignant behavior (carcinoma vs adenoma):

capsular invasion

vascular invasion

greater mitotic rate

Fig. 4.1

Figs 4.1–4.2 Photographs of a resected adrenocortical carcinoma, measuring more than 10cm in maximum extent, the cut surface showing a solid tan yellow appearance with areas of necrosis.

Fig. 4.3

Fig. 4.4

Fig. 4.5

Fig. 4.6

Figs 4.3–4.7 Photomicrographs of a case of adrenocortical carcinoma in a child, demonstrating focal necrosis and marked nuclear pleomorphism. There was also capsular and vascular invasion and local recurrence appeared soon after surgery.

Immunohistochemical staining

• Alpha inhibin+

• Chromogranin negative (cf medullary tumors)

• May be only weakly positive for cytokeratin and EMA

• CEA negative

Differential diagnoses and pitfalls

• Smaller lesions difficult to predict clinical behavior from histological features

• May be related to germ-line point mutation of p53 even with no positive family history, acting in a tissue-specific manner (Ribeiro et al 2001)

PHAEOCHROMOCYTOMA

• Tumor of chromaffin cells of adrenal medulla

paraganglioma if affecting other sites

• Benign (90%)

• Malignant (10%: strictly defined by metastases)

Epidemiology

• Mainly sporadic

• >10% associated with NF-1, MEN2, VHL and/or familial cases

these more likely to present at younger age

Buy Membership for Pathology Category to continue reading. Learn more here

[/not-level-membership-for-pathology-category]

Diagnostic Pediatric Surgical Pathology Expert Consult--Online a