Global Cancer Care: Diagnostic Pathology. Dr. Michael Wilson, University of Colorado September 17, 2016 ASCP Annual Meeting Sessions 9104 & 9105

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1 Global Cancer Care: Diagnostic Pathology Dr. Michael Wilson, University of Colorado September 17, 2016 ASCP Annual Meeting Sessions 9104 & 9105

2 Global Cancer Care: Diagnostic Pathology In the past 12 months, I have not had a significant financial interest or other relationship with the manufacturer(s) of the product(s) or provider(s) of the service(s) that will be discussed in my presentation.

3 Global Cancer Care: Diagnostic Pathology General Concepts Regarding Global Health Partners in Cancer Diagnostics and Treatment in Sub-Saharan Africa Diagnostic Considerations in Global Health Questions/Discussion

4 Diagnostic Considerations in Lymphadenopathy Global Health Differential Diagnosis Different Than in USA/EU Presentation is Often Later in Disease Course Co-Morbidity: Higher Incidence of HIV Infection, Chronic Malaria, Tuberculosis, Others

5 Diagnostic Considerations in Lymphadenopathy Global Health Nigeria: 14-year Retrospective Histopathologic Study of 720 Lymph Node Biopsies at Lagos University Teaching Hospital Chronic Non-Specific Lymphadenitis 245 (34%) Tuberculosis 125 (17.4%) Metastatic Lesions 242 (33.6%) Lymphomas 102(14.2%) Most Common Lymph Node Group: Cervical 283 (39.3%) Anunobi CC, Banjo AA, Abdulkareem FB, Daramola AO, Abudu EK Review of the histopathologic patterns of superficial lymph node diseases, in Lagos ( ). Niger Postgrad Med J 2008;15:243-6

6 Diagnostic Considerations in Lymphadenopathy Global Health Malawi: Cross-Sectional Study of Cervical Lymph Node Specimens From Kamuzu Central Hospital 179 Cases: 143 (77%) Histopathology, 34 (23%) Cytology Adults: Most Common Diagnosis Was Malignancy (n=41, 35%) Children: 15 Cases Each of Malignancy And Benign Masses Only 6 Cases (5%) of TB in Adults, 4 Cases (6%) in Children Mabedi C, Kendig C, Liomba G, Shores C, Chimzimu F, Kampani C, Krysiak R, Gopal S. Causes of cervical lymphadenopathy at Kamuzu Central Hospital. Malawi Med J 2014;26:16-9

7 Diagnostic Considerations in Lymphadenopathy Global Health Nigeria: 15-Year Retrospective Review of 1,180 Superficial Lymph Node Biopsies, University of Nigeria Teaching Hospital 172 Cases of TB (14.6%), 23 HIV-Infected Acid-Fast Bacilli Seen in 15.1% (26/172) of Cases (Ziehl-Neelsen) Most Common Site for TB Was Cervical 127/172, 73.8%), Axillary (24/172, 14%), and Inguinal (8/172, 4.7%) Remarkable Decline in TB Lymphadenitis in South-Eastern Nigeria. Ukekwe FI, Olusina DB, Banjo A, Akinde OR, Nzegwu MA, Okafor OC, Ocheni S. Tuberculous Lymphadenitis in South- Eastern Nigeria: A 15 Year Histopathologic Review ( ). Ann Med Health Sci Res 2016;6:44-9

8 Diagnostic Considerations in Global Health Lymphadenopathy - Infectious Approach to Evaluation Different From USA/EU Availability of Ancillary Studies Such as Microbiological Cultures Often Limited Availability of Immunohistochemical Stains/ISH Often Limited Histopathologic Findings Can Vary For Some Infections

9 Diagnostic Considerations in Global Health Lymphadenopathy Infectious If Available, Cultures Should be Performed Bacterial, Fungal, Mycobacterial Histopathologic Correlation With Clinical Findings And/or Culture Results is Critical Viral Lymphadenopathy Not as Common But Does Occur

10 Diagnostic Considerations in Global Health Lymphadenopathy Infectious Use of Molecular Tests Still Limited Tanzania: 75 Children With Lymphadenopathy Against Composite Reference Standard: Sensitivity Specificity Xpert MTB/RIF 58% 93% EasyNAT 19% 100% Cytology 100% 94.7% Bholla M, Kapalata N, Masika E, Chande H, Jugheli L, Sasamalo M, Glass TR, Beck HP, Reither K. Evaluation of Xpert MTB/RIF and Ustar EasyNAT TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania: a prospective descriptive study. BMC Infect Dis 2016;16:246

11 Case Clinical History 32-Year-Old Female Presents With Fever, Non- Productive Cough, Pleuritic Chest Pain, Fatigue No Previous Medical Care at Hospital

12 Case Clinical Findings Febrile Non-Tachycardic Tachypneic In Mild Distress

13 Case Radiographic Findings Multiple Cavities And Scarring of Right Lung No Acute Infiltrates Minimal Hilar Lymphadenopathy Enlarged Cervical Lymph Nodes

14 Case Laboratory Findings Normal Total White Blood Cell Count Mild Normocytic/Normochromic Anemia Sputum Smears X3 Negative For Mycobacteria Sputum Cultures X3 Negative For Mycobacteria

15

16

17 Case Clinical-Pathological Correlation Clinical History Suggests TB Radiographic Findings Consistent With Old TB Laboratory Findings Not Consistent With Active TB

18 Case Lessons Learned Most American Hospitals Have 0-5 Annual TB Cases Not All Medical Providers Are Experienced With Treating Patients With Suspected TB Lack of Experience With Complicated TB Cases

19 Diagnostic Considerations in Global Health Lymphadenopathy Neoplastic Geographic Variation in Burkitt s Lymphoma HIV Co-Infection and Kaposi s Sarcoma Parasitic Infections Common in Some Regions Metastatic Tumors Not Uncommon

20 Diagnostic Considerations in Global Health Questions?

21 Session number 9105 Pathology in Africa: Skin ulcers and eschars Jeannette Guarner, MD Department of Pathology and Laboratory Medicine Emory University

22 Conflicts: none Disclosures: Paid by The Emory Clinic Worked at CDC , now guest researcher Brought up in Mexico, thus funny accent Husband, at Emory University, Chair of Global Health Images, own and from CDC: In the past 12 months, I have not had a significant financial interest or other relationship with the manufacturer(s) of the product(s) or provider(s) of the service(s) that will be discussed in my presentation. This presentation will include discussion of pharmaceuticals or devices that have been approved by the FDA or unapproved or "off-label" uses of pharmaceuticals or devices.

23 Case 22-year-old male from Ghana presents with an ulcer in the right arm (shown). The lesion started as a nodule 8 months ago. The nodule expanded and ulcerated. In the last 4 months the ulcer has extended and deepened

24 Considerations Ulcers are major source of morbidity (pain, swelling, drainage, limitations in mobility, depression, social interactions). Take considerable time to heal. Secondary infections. End product of different conditions: In legs think of neuropathy or vascular insufficiency first (diabetes, vasculitis) Others are considered chronic inflammatory ulcers J Panuncialman, V Falanga. Unusual causes of cutaneous ulceration. Surg Clin North Am 2010;90:1161

25 Differential diagnosis of chronic inflammatory ulcers Diseases at site of inoculation (anthrax, rickettsiosis, spider bites, myiasis, mycobacteria) Genital lesions (herpes, chancroid) Hematogenous lesions (cryptococcosis, pyoderma gangrenosum, mycobacteria) Malignancies (squamous or basal cell carcinoma)

26 Approach to diagnosis History: how did it start, how long has it been going on, associated pain, exposures, management given. Physical exam: surrounding skin (vascular and neural), systemic diseases, A Freedman et al. Cutaneous anthrax associated with microangiopathic hemolytic anemia and coagulopathy in a 7-month old infant. JAMA. 2002;287:

27 When should a biopsy be considered? Ulcers of undetermined cause Any ulcer that is refractory to treatment for at least 3 months Suspicion of malignancy Chronic ulcers ulcers can develop malignant transformation (mostly squamous cell carcinoma) G Spentzouris, N Labropoulos. The evaluation of lower extremity ulcers. Semin Intervent Radiol 2009;26:286

28 Where to take the biopsy? Sample that includes the surrounding skin and the wound bed.

29 EXAMPLES

30 Buruli ulcer Caused by Mycobacterium ulcerans Produces mycolactone (toxin that destroys tissue). Affects primarily children under 15 that live in rural communities Lesions present in lower limbs (55%), upper limbs (35%), other parts 80% of cases detected early can be cured with combination antibiotics.

31

32 Guarner J et al. Histopathologic features of Mycobacterium ulcerans infection. Emerg Infect Dis 2003;:

33

34

35 Anthrax September 25, 2001 in New York City: Secretary working at NBC developed a cutaneous lesion. She received antibiotics. Cultures of lesion not obtained. October 12, 2001: Culture and PCR of biopsy obtained 9 days after treatment: negative for B. anthracis. IHC on biopsy showed anthrax antigens. Serology eventually confirmed IHC result.

36 Histopathology

37 Gram Special stains Inhalational anthrax Cutaneous anthrax Positive with Gram stain 3/8 (37.5%) 2/10 (20%) Positive with silver stains (Steiner or Warthin Starry) 6/8 (75%) 5/10 (50%) Steiner

38 Spider bite (brown recluse) -7 month old child with rapidly appearing eschar, minimal edema -Afebrile, WBC 23K, Gram stain unrevealing -Mother works in laboratory where anthrax is studied extensively

39 Rickettsiosis

40 Rickettsia akari Paddock et al. Ann N Y Acad Sci 2003;990:36.

41 Case history -40 y/o man with fever, headache, diffuse mylagias -Residence bordering tidal estuary in VA -Erythematous vesicular rash and multiple eschars

42 Rickettsia parkeri Paddock et al. Clin Infect Dis 2004;38:805

43

44 Monkeypox Primary inoculation lesion at site of prairie dog bite Secondary lesions

45 The Washington Post, June 9, 2003 BMJ 2003;326:1350.

46

47 Viral culture

48

49 Case A 5 years old girl with ALL. WBC count of 10,000. During the second week of induction she developed two red lesions over medial aspect of left forearm that in a matter of days expanded and turned black. Three antibiotics (ceftazidime, amikacin and vancomycin) were started, but with no improvement.

50 Histopathology shows

51

52 Case 37 year old Ethiopian female with a Phylloides tumor. Her mother brought an Ethiopian healing poultice for her wound. A week later she has difficulty swallowing and spasms and stiffness of the jaw. A culture is obtained and the wound revised.

53

54

55

56 Gram stain from anaerobic colony

57

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