DERMATOPATHOLOGY PATHOLOGY OF ENDOCRINE SYSTEM

Thyroid carcinoma, Hashimoto thyroiditis, Graves‘ disease, neuroendocrine tumor, Institute of Pathological Anatomy melanoma, pigmented naevus, psoriasis, eczema FM CU BA

DERMATOPATHOLOGY • 10-year-old boy with a pigmented lesion on his shoulder, sharply demarcated from the surrounding skin, with a diameter of 2.3 cm, dark brown in color, without noticeable changes. CASE NO. 1 ➢Suggested examinations? ➢Your diagnosis? ➢Describe the microscopic finding. Pigmented nevus of the skin Congenital pigmented nevus of the skin PIGMENTED NEVUS

• benign skin formation arising as a result of melanocyte accumulation • the most common skin lesion of the white race • most nevi form in childhood and adolescence Classification of nevi according to the position of growth in the skin • Junctional nevus - nests of melanocytes are found at the dermo-epidermal junction • Mixed nevus - nests of melanocytes are found at the junction but also in the dermis • Intradermal nevus - clusters of melanocytes are found in the upper part of the dermis WITHOUT connection with the epidermis Histological variants of pigmented nevus • Congenital nevus • Blue nevus • Halo nevus • Familial dysplastic nevus Mixed pigmented nevus

Junctional pigmented nevus Intradermal pigmented nevus • 73-year-old patient was admitted to hospital for progressive weakness, shortness of breath. You notice that both the skin and the sclera are icteric. • laboratory hyperbilirubinemia, hypoalbuminemia and mineral imbalance, positive oncomarkers (S100) • abdominal ultrasound with spherical structures found in the liver parenchyma • personal medical history - malignant melanoma of the eye CASE NO. 2 30 years ago, CLL 3 years ago, now in remission

➢Suggested examinations? ➢Your diagnosis? ➢Complications? ➢Describe the microscopic finding. Metastasis in right lungs Small subpleural metastases Metastasis of malignant melanoma in lung parenchyma Brain with petechial hemorrhages near basal ganglia Brain Tiny metastases to kidney and stomach Melanoma metastases to liver Malignant melanoma metastasis to liver Malignant melanoma MELANOMA • malignant proliferation of melanocytes (skin, eye, ...) • histologically we recognize many variants (superficially spreading melanoma, lentigo maligna, acral melanoma, nodular melanoma) • in the etiology, UV radiation (geographical parameter), familial dysplastic nevi syndrome, congenital nevus, immunosuppression, pale skin type are important ABC diagnostics for melanoma ✓ A - asymmetry ✓ B - irregular borders ✓ C - pigmentation change (color) ✓ D - growth of skin lesion (diameter) ✓ E - lesion evolution

➢ melanomas may be associated with a BRAF gene mutation (V600E), in which they may receive targeted therapy ➢ Breslow's assessment of the depth of melanocyte invasion is an important prognostic feature • 34-year-old man comes to your clinic for a long-lasting forearm rash • the skin lesion is map-like, sharply demarcated from the adjacent skin, light pink, on the surface with silvery scales, after the removal of the scales a spotting bleeding appears at the base CASE NO. 3 • similar lesions are found on the head, elbows and knees • patient also has arthritic manifestations

➢Suggested examinations? ➢Your diagnosis? ➢Describe the microscopic finding.

Psoriasis – papillary dermal edema, hyper- and parakeratosis, widened epidermal papillae PSORIASIS

• non-infectious inflammatory autoimmune skin disease with a chronic course and a tendency to relapses • the most common manifestation is peeling of the skin, because it renews up to seven times faster than normal Microscopic findings • hyperkeratosis with focal or confluent parakeratosis • regular psoriaform acanthosis – widely broadened epidermal processes (acanthotic pins) • dermal papillary edema • suprapapillary thinning of the epidermis • stratum granulosum is not present • focal infiltration by neutrophilic granulocytes in parakeratosis ➢ Munro‘s microabscesses in the parakeratotic corneal layer - diagnostic criterium • as part of a counseling session, you are examining a 1-year-old child when you notice reddening of the skin on the face, cubital fossae and knees. According to parents, these spots appear and disappear and are itchy. They have appeared and disappeared randomly in the last 6 months. • pregnancy and childbirth were without complications CASE NO.4 • both parents are healthy, the father has asthma and has a seasonal allergy

➢Suggested examinations? ➢Your diagnosis? ➢Describe the microscopic finding. Atopic eczema

ATOPIC ECZEMA

• chronic, recurrent skin disease • reduction of the lipid skin barrier, which leads to increased water loss and thus reduced skin hydration • alternation of exacerbations and remissions • multifactorial disease without a specific genetic cause Triphasic occurrence • Infant period (1 - 2 years) • Childhood period (2 - 12 years) • Adolescent and adult phase (over 12 years) Histopathologic skin changes • Acute phase - skin spongiosis, perivascular lymphocytic infiltrate in the dermis • Subacute phase - a combination of signs of acute and chronic phase • Chronic stage - acanthosis, hyperkeratosis, lymphocyte infiltrate in the dermis • psoriasis is a chronic, non-infectious, inflammatory disease typically manifested by silver scales on the surface of the skin • epidermal spongiosis and lymphocyte infiltrate in the dermis are typical findings in skin eczema • hypopigmentation and hyperpigmentation are the SUMMARY result of changes in melanocyte proliferation or melanin • melanocyte nevus is a consequence of focal proliferation of melanocytes • superficial ulceration, depth of invasion (Breslow) and mitotic activity are important prognostic markers of malignant melanoma PATHOLOGY OF ENDOCRINE SYSTEM • 42-year-old woman has been treated for depression for a prolonged period of time. At the periodic examination, the patient describes that she is constantly tired and sleepy, complaining of deteriorating hair quality. She has recently gained weight, but without a change in diet. • physical examination - pulse frequency 52 / min, slower reflexes, you notice swelling of the face and eyelids • Recently, she noticed that her neck had also enlarged - she could not put on her favorite necklace. She feels that CASE NO. 5 medication for depression does not work.

➢Suggested examinations? ➢Your diagnosis? ➢Complications? ➢Describe the microscopic finding. Hashimoto's thyroiditis Hashimo's thyroiditis – lymphocyte-plasma cell infiltrate with formation of lymphatic follicles with germinal centers Lymphatic follicles

Remnants of thyroid follicles

Hashimoto's thyroiditis HASHIMOTO'S THYROIDITIS

• chronic autoimmune lymphocytic goiter, the most common cause of hypothyroidism • mainly affects middle-aged women • predisposing factors are another autoimmune disease, the presence of HLA-DR5 and HLA-B5 • laboratory present Ab against aTG, against thyroperoxidase aTPO, Ab against TSH receptors

➢ Diagnostic criteria - triad - diffuse enlargement of thyroid gland, infiltration of Lym, + autoAb against thyroid gland, hypothyroidism, medium-sized goiter ➢ patients with advanced Hashimoto‘s thyroiditis have significantly higher change of developing primary B (MALT) lymphoma • 35-year-old woman visits you due to constant feelings of a strong noticeable heartbeat, she constantly feels very hot • she likes to eat plenty and she is still hungry, although she has not gained any weight. Her husband told her she had been acting irritated lately. • physical examination - exophthalmos, moisty skin, pulse CASE NO. 6 110 / min, you feel a diffusely enlarged thyroid gland.

➢ Suggested examinations? ➢ Your diagnosis? ➢ Complications? ➢ Describe the microscopic finding. Graves‘ disease Graves‘ disease - hyperplasia of follicular cells with pseudopapillary structures protruding into the lumen of follicles, they contain a smaller amount of vacuolated colloid GRAVES‘ DISEASE

• autoimmune thyroid disease - the most common cause of hyperthyroidism • mainly affects middle-aged women • laboratory: elevated serum values of T3 and T4, decreased TSH, Ab against TSH receptors • anti-TSH receptor antibodies have a stimulatory and growth effect • the disease is often associated with other autoimmune diseases, in individuals with HLA- DR3 and HLA-B8

➢ Diagnostic criteria - triad of symptoms - thyrotoxicosis, diffuse enlargement of thyroid gland, exophthalmos ➢ these patients have a markedly increased risk of thyroid cancer •59-year-old man without history of diseases, except for dyslipidemia and abdominal aortic aneurysm in obeservation by cardiologist • visit his GP for cough, hoarseness of voice and odynophagia • for years he was a heavy smoker and quit 15 years ago, alcohol is estimated at 2-3 beers a day. Due to the clinical picture, he was diagnosed with laryngitis. • over time, the pain disappeared when swallowing, but the chronic cough and hoarseness persists despite treatment. The patient has no CASE NO. 7 symptoms of hypo- / hyperthyroidism. • endosonography revealed a tumor invasion of the muscularis propria distal to the upper esophageal sphincter, laryngoscopy showed paralysis of the left vocal cord.

➢ Suggested examinations? ➢ Your diagnosis? ➢ Complications? ➢ Describe the microscopic finding. Thyroid carcinoma Papillary carcinoma

Thyroid follicles

Nonencapsulated infiltrative tumor Epithelial papillary projections into gland-like spaces, epithelial cells with nuclear clearing Follicular carcinoma - uniform microfollicles THYROID GLAND CARCINOMA • a heterogeneous group of diseases with different morphology and clinical manifestations • represents the most common tumors of the entire endocrine system (90%) • predominantly solitary nodules in the thyroid parenchyma • the most common histological type is papillary carcinoma

Classification of thyroid tumors Benign tumors - adenoma 1. Malignant tumors a) primary tumors epithelial: papillary, follicular, medullary, anaplastic non-epithelial: malignant lymphoma, sarcoma b) secondary tumors (metastasis of breast Ca, lung, kidney) • 35-year-old woman has recently been complaining of severe heartbeat without exertion, frequent loose stools, itchy skin and hot flushes. During the conversation with the patient, strong redness appears on the face and neck. CASE NO. 8 ➢Your diagnosis? ➢Suggested examinations? ➢Complications ➢Describe the microscopic finding. Neuroendocrine tumor of the small intestine Neuroendocrine tumor of the small intestine – typical „salt and pepper“ appearance of nuclei CD56

synaptophysin

General cytokeratins

Neuroendocrine tumor of the small intestine NEUROENDOCRINE TUMORS

• a group of tumors capable of secreting biogenic amines • thus part of the APUD or the diffuse neuroendocrine system • mainly in the GIT and in the respiratory tract - according to the locality the classification varies • always malignant tumors • mainly in the GIT they secrete hormones, especially serotonin (glucagonoma, insulinoma, ...)

➢ Carcinoid syndrome - a set of non-specific clinical symptoms due to the secretion of biogenic amines from the tumor (tachycardia, flash on the face and chest, diarrhea, ...) • Graves‘ goiter is an autoimmune disease that stimulates the thyroid gland • Hashimoto's disease is an autoimmune disease associated with hypothyroidism • clinical manifestations and prognosis of thyroid tumors SUMMARY are related to the histological type of the tumor • papillary thyroid carcinoma is diagnosed on the basis of nuclear features • neuroendocrine tumors can occur anywhere on the body, they are always malignant • NET are most often found in the GIT