L14: Male reproductive pathology SCBM 342 Systemic pathology

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1 Edited: 20-Feb-2018 L14: Male reproductive pathology SCBM 342 Systemic pathology Nisamanee Charoenchon, PhD Department of Pathobiology, Faculty of Science

2 Male genital system pathology - Penis - Testis, Scrotum, Epididymis, Spermatic cord - Prostate gland

3 Penis Congenital anomalies Inflammation Tumors

4 Testis and Epididymis 1. Congenital anomaliess 2. Regressive change 3. Inflammation Specific imflammation 1. Gonorrhea 2. TB 3. Mumps 1. Spermatic cord and 2. Paratesticular tumors 3. Testicular tumors 4. Vascular tumors

5 PENIS

6 Congenital disorder of Penis * Agenesis ( Apenia ) * Hypoplasia ( Micropenis ) Phimosis Hypospadias, Epispadias (=absence of the penis)

7 PHIMOSIS OF PENIS opening of prepuce too small to retract backward Collection of necrotic & desquamated cells (of a layer of cells, e.g., of the skin) come off in scales or flakes. under prepuce called SMEGMA, = carcinogenic & may lead to squamous cell carcinoma of penis

8 => Frequent occurring bacterial infection of glans penis & prepuce ( balanoposthitis ) => May cause fibrotic structure of penis ( paraphimosis )

9 May cause fibrotic structure of penis (inflammation of the glans, the rounded head of the penis)

10 Comparison phimosis & normal penis Penis with phimosis Normal penis

11 Hypospadias

12 Hypospadias urethral opening ectopically located on ventrum of the penis may be as far down as in the scrotum / perineum.

13 Comparison Hypospadias & normal

14 Types of hypospadias

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16 Penile epispadias

17 Inflammatory disorders of Penis 1. Peyronie s disease 2. Balanitis xerotica obliterans ( BXO ) 3. Bacterial balanoposthitis 4. Sexually transmitted diseases (STD)

18 1. Peyronie s disease of penis (Fibromatosis).. chronic inflammation of the tunica albuginea, the cause,not well understood,maybe trauma /injury.. produces a bent penis during erection... fibrous scar tissue inside the penis, causes curved, painful erections

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21 Peyronie s disease of penis (Fibromatosis) Fibrotic area

22 2. Balanitis xerotica obliterans (BXO) Lichen sclerosus (LS) is a skin disease of unknown cause, commonly appearing as whitish patches on the genitals, which can affect any body part of any person but has a strong preference for the genitals (penis, vulva) is a chronic, often progressive disease, which can lead to phimosis and urethral stenosis, affecting both urinary and sexual function.

23 Histopathology Balanitis xerotica obliterans Hyperkeratosis of epithelium Sclerotic beneath epithelium

24 Balanitis xerotica obliterans ( BXO ) chronic, progressive, sclerosing inflammatory (skin) a disease of the skin dermatosis of unclear etiology... can lead to phimosis & urethral stenosis,

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26 3.1 GONORRHEA OF PENIS by NEISSERIA GONORRHEA (Gram negative coci) - Coffee bean shape - Diplococcus - A bacterium responsible for the sexual transmitted

27 Pus from urethra GONORRHEA (GONOCOCCAL URETHRITIS)

28 Gram stain of pus from urethra in gonorrhea Gonococci in cytoplasm of neutrophil

29 3.2 Primary SYPHILIS of penis - Treponema pallidum chan cre ˈkaNGkər,ˈSHaNGkər/ It causes one or more small, painless sores in or around the genitals, anus, or mouth. Painless sore แผล Chancre (รอยโรคจะปรากฏเป นแผลร มแข ง) ค อม ล กษณะ แผลขนาดเล ก ส ณฐานกลม น ม และ ไม เจ บปวด (แผลน บางท อย ในท ท ไม สามารถมองเห นได เราก จะไม ร ว าม แผล)

30 Treponema pallidum is a spirochaete bacterium with subspecies that cause treponemal diseases such as syphilis

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32 Primary SYPHILIS ( Hard chancre) ˈkaNGkər,ˈSHaNGkər/

33 Spirochetes from syphilitic ulcer

34 Skin lesion in secondary syphilis Cutaneous secondary syphilis: the skin manifestations of secondary syphilishave been called syphilids and occur in >80% of cases. Widespread rash and 'flulike symptoms appear next (secondary syphilis). All cutaneous and mucous membrane lesions of secondary syphilis contain treponemes

35 Stage I, primary syphilis local invasion: Treponema pallidum multiplies in epithelium, producing granulomatous tissue reaction (chancre); lymph-containing microorganisms drain into adjacent lymph nodes and stimulate immune responses Stage II, secondary syphilis systemic disease: blood-borne bacteria spread to all major organ systems; immune system suppresses infection and symptoms regress spontaneously Stage III, latent syphilis silent infection: transmission of infection possible even though there are no clinical signs of infection Stage IV, tertiary syphilis noninfectious disease: significant morbidity and mortality occur; destructive skin, bone, and soft tissue lesions, or gummas, result from severe hypersensitivity; cardiovascular complications (aneurysms, heart valve insufficiency, heart failure) and neurosyphilis develop

36 4.1 Condyloma of penis Caused by human papilloma virus (HPV) Most are sexually transmitted, % of men are partners of women with HPV infection Incubation period is from 3 months to years Non dysplastic lesions produced by HPV type 6 dysplastic / precancerous lesions are caused by HPV types 16, 18, 31, 33, 35 Usually seen in young adults, treatment by laser / topical podophyllin

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38 Gross appearance of condyloma of penis There are 3 types of gross appearance 1. Condyloma acuminatum (most common) 2. Condyloma plana (flat wart),.. flesh color small papules 3. Bowenoid papulosis, multicentric lesions in young adults on penile shaft / perineum caused by HPV type 6, 16, 39 usually shows spontaneous regression, some authors classified as precancerous lesion

39 Condyloma acuminatum Bowenoid papulosis Condyloma plana

40 Condyloma acuminatum Histopathology of condyloma acuminatum - papillomatosis of epithelium - ballooning cells with hyperchromatic nuclei ( koilocytotic change ) - no invasion into underlying stroma - mild lymphocytic infiltration in subepithelial tissue A koilocyte is a squamous epithelial cell that has undergone a number of structural changes, which occur as a result of infection of the cell by human papillomavirus.

41 Condyloma acuminatum of penis

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43 Histopathology: condyloma acuminatum ballooning cells/ vacuolization ( koilocytosis)

44 Condyloma acuminatum of penis Note ballooning cells/ vacuolization ( koilocytosis)

45 4.2 Herpes simplex viral infection of penis Caused by Herpes simplex virus type 2 (HSV-2) Gross appearance as. groups of small vesicles turning to ulcers Self remission but usually has several recurrences Intra nuclear inclusion body (Cowdry type A) & multi -nucleation of epithelial cell nuclei are characteristic

46 Herpes Simplex infection Group of vesicles

47 HERPES SIMPLEX INFECTION OF PENIS Group of vesicles Early ulceration

48 Herpes simplex viral infection of penis multi -nucleation of epithelial cell nuclei Intranuclear inclusion body Inclusion bodies, sometimes called elementary bodies, are nuclear or cytoplasmic aggregates of stable substances, usually proteins. They typically represent sites of viral multiplication in a bacterium or a eukaryotic cell and usually consist of viral capsid proteins.

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50 ˈkaNGkər Soft chancre (Chancroid) from Hemophilus ducreyi Ulcer contains yellowish exudate Haemophilus ducreyi is a fastidious gram-negative coccobacillus bacteria,

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53 Soft chancre from Hemophilus ducreyi โรคแผลร มอ อน Enlarged inguinal lymph node in soft chancre

54 Differences in clinical appearance among chancroid, syphilis, and genital herpes. (From Morse SA et al, editors:atlas of sexually transmitted diseases and AIDS, ed 4, London, 2013, Saunders.)

55 Fournier gangrene of penis from severe infection in diabetes

56 Precancerous lesions of Penis BOWEN S DISEASE - squamous cell carcinoma in situ of penis - 11% will turn into invasive squamous cell carcinoma - usually associated with visceral cancer - gross lesion is single,erythematous,scaling plaque (a,b) Flat plaques were observed on the base of the penis, and two nodules were observed on the dorsal plane of the penile shaft. (c) A 3-cm diameter plaque with yellowish crusts was observed in the perianal region.

57 (e) penile shaft lesion (hematoxylin eosin [HE], bar = 200 μm) Bowen's disease, also known as squamous cell carcinoma in situ is a neoplastic skin disease. It can be considered as an early stage or intraepidermal form of squamous cell carcinoma.

58 ERYTHROPLASIA OF QUEYRAT - lesion at glans penis, squamous cell carcinoma in situ - gross lesion is erythematous plaque Erythematous plaque on ventral surface of penile shaft with a sharply defined thready

59 Precancerous lesions of Penis Bowenoid papulosis Although most cases of Bowenoid papulosis are benign (harmless) a small percentage may transform into invasive squamous cell carcinoma(penile or vulvar cancer). Occurring in young adults usually at penile shaft or perineum Associated with HPV type 6,16,39 Spontaneous regression is common Few cases can progress to squamous cell carcinoma

60 BOWEN S DISEASE squamous cell carcinoma in situ of penis gross lesion is.. single, erythematous, scaling plaque

61 TESTIS

62 Undescended testes (or cryptorchidism) is a condition when one or both of the testes have not descended into the scrotum at birth, but stay in the abdomen or only move part way down into the scrotum. CRYPTORCHIDISM

63 CONGENITAL DISORDERS OF TESTIS CRYPTORCHIDISM ( UNDESCENDED TESTIS ) Testis is not in scrotum (usually unilateral) - may be at inguinal canal / in abdominal cavity - can not produce spermatozoa - marked increased incidence of germ cell tumor in undescended testis, most common is seminoma (malignant) Seminoma (also known as pure seminoma or classical seminoma) is a germ cell tumor of the testicle or, more rarely, the mediastinum or other extra-gonadal locations.

64 Locations of undescended testis 48%

65 Testicular atrophy is a medical condition in which the male reproductive organs (the testes, which in humans are located in the scrotum) diminish in size and may be accompanied by loss of function. This does not refer to temporary changes, such as those brought on by cold.

66 Testicular atrophy

67 Normal TESTIS + active Spermatogenesis SPERMATOZOA both testosterone & follicle - stimulating hormone (FSH) is needed to support spermatogenesis

68 NO Spermatogenesis in Undescended Testis Sertoli cell only in atrophic tubule Mark increased interstitial Leydig cells

69 Leydig cells (15-20 µm), Testis - located in interstitial tissue bet. convoluted seminiferous tubules, constitute endocrine cpn of testis - synthesise & secrete testosterone - occur in clusters,variable in size & richly supplied by capillaries. - cytoplasm strongly acidophilic & finely granular. - nucleus is large, round & often located eccentric in the cell Sertoli cells - extend from BM to luminal surface of seminiferous epithelium. - Their processes s extend in bet spermatogenic cells - nucleus is ovoid / angular, large & lightly stained & contains a large nucleolus - provide mechanical & nutritive support for spermatogenic cells. - also secrete hormones- inhibin & activin - positive & negative feedback on FSH secretion

70 Testis Courtesy of llustration from Anatomy & Physiology, Connexions Web site. Jun 19, 2013.

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72 Carcinoma

73 Squamous cell carcinoma of Penis Usually associated with phimosis Human papilloma virus/ HPV type 16 & 18 may be the cause patients usually over 40 years old usually metastasize to inguinal LN

74 Penile squamous cell carcinoma

75 Penile squamous cell carcinoma Advanced squamous cell carcinoma of penis

76 Histopathology of squamous cell carcinoma

77 Staging of Squamous cell carcinoma of penis STAGE I -- tumor confines to glans penis + prepuce STAGE II -- invades into shaft of penis STAGE III -- metastasize to inguinal LN, still resectable STAGE IV -- metastasize into inguinal LN, but unresectable / distant metastasis

78 Advanced carcinoma of penis with metastasis Inguinal LN metastasis

79 VERRUCOUS CARCINOMA OF PENIS Other name = giant condyloma of Bushke- Loewenstein, unknown cause gross lesion is papillary exophytic lesion local invasion to nearby stroma, but no metastasis usually has frequent recurrence even with complete resection no cytologic atypia in histopathology

80 Verrucous carcinoma of penis ( = giant condyloma )

81 Histopathology of verrucous carcinoma showing papillomatosis & hyperkeratosis

82 Histopathology of verrucous carcinoma showing smooth bulbous ( rounded/ swollen) lower part of lesion

83 MALIGNANT MELANOMA OF PENIS Can occur on glans penis / prepuce Cell of origin is melanocyte Pathology : Irregular & satellite lesion

84 MALIGNANT MELANOMA OF PENIS Histopathology: malignant melanoma in dermis & epidermis

85 MALIGNANT MELANOMA OF PENIS Focus black pigment in cytoplasm