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Case 20: 46 yo Female, ASCUS PAP, + for High-risk HPV

Richard W. Lieberman, MD Department of Anatomic Pathology and Obstetrics & Gynecology. Case 20: 46 yo Female, ASCUS PAP, + for High-risk HPV. Case 20: Presentation. 46 year old female Repeatedly abnormal cervical cytology ASCUS, positive for high risk HPV by HC2

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Case 20: 46 yo Female, ASCUS PAP, + for High-risk HPV

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  1. Richard W. Lieberman, MD Department of Anatomic PathologyandObstetrics & Gynecology Case 20:46 yo Female, ASCUS PAP, + for High-risk HPV

  2. Case 20: Presentation • 46 year old female • Repeatedly abnormal cervical cytology • ASCUS, positive for high risk HPV by HC2 • Multiple colposcopic examinations • Biopsy diagnosis: Chronic cervicitis • Representative Colposcopic image of Cervix: • Slightly enlarged, erythematous,non-specific acetowhite changes Case 20: New Frontiers in Pathology 2010

  3. Case 20: • LEEP Procedure performed to evaluate recurrent unexplained ASCUS-HPV positive testing • Working diagnosis:inflammatory pseudotumor of cervix • Case referred for review by UMHS Hematopathology not a lymphoid proliferation, consult to Gyn Path Case 20: New Frontiers in Pathology 2010

  4. Case 20: Some Additional History • PMH: • Chronic schizophrenia • Lives in a group home • No other history available Case 20: New Frontiers in Pathology 2010

  5. LEEP of cervix, low power Case 20: New Frontiers in Pathology 2010

  6. LEEP – 2x Epithelium Thinned with inflammatory changes Reactive change, without definitive SIL Stroma Mixed inflammatory infiltrate Lymphocytes and plasma cells Perivascular condensation “spindled–cell” stroma with mitoses noted Case 20: New Frontiers in Pathology 2010

  7. LEEP – 10x Epithelium Thinned with inflammatory changes Reactive change, without definitive SIL Stroma Mixed inflammatory infiltrate Lymphocytes and plasma cells Perivascular condensation “spindled–cell” stroma with mitoses noted Case 20: New Frontiers in Pathology 2010

  8. LEEP – 20x Epithelium Thinned with inflammatory changes Reactive change, without definitive SIL Stroma Mixed inflammatory infiltrate Lymphocytes and plasma cells Perivascular condensation “spindled–cell” stroma with mitoses noted Case 20: New Frontiers in Pathology 2010

  9. Case 20: New Frontiers in Pathology 2010

  10. Case 20: Differential Diagnosis • Inflammatory myofibroblastic tumor (IMT) • aka invasive or inflammatory pseudotumor • Pseudosarcomatous myofibroblastic proliferations • Plasma cell granuloma • Cervicovaginal myofibroblasoma • Angiomyofibroblastoma • Post-operative spindle cell nodule • Smooth muscle tumor • Spindle cell carcinoma Case 20: New Frontiers in Pathology 2010

  11. Additional Testing: What would you order? Histochemical Stains Immunohistochemical Stains • B&H • GMS • Warthin-Starry (Steiner) • Cytokeratin • ALK-1 • Smooth muscle actin • Vimentin • Others? Case 20: New Frontiers in Pathology 2010

  12. Case 20: Differential Diagnosis • Inflammatory myofibroblastic tumor (IMT) • aka invasive and inflammatory pseudotumor • Pseudosarcomatous myofibroblastic proliferations • Plasma cell granuloma • Cervicovaginal myofibroblasoma • Angiomyofibroblastoma • Post-operative spindle cell nodule • Smooth muscle tumor • Spindle cell carcinoma Well circumscribed,No Grenz zone No recent surgery. Desmin, SMA neg. Keratin negative Vulvar, well circumscribed Case 20: New Frontiers in Pathology 2010

  13. Additional Testing: What would you order? Histochemical Stains Immunohistochemical Stains • B&H • GMS • Warthin-Starry (Steiner) • Cytokeratin • ALK-1 • Smooth muscle actin • Vimentin • Others? Case 20: New Frontiers in Pathology 2010

  14. Warthin-Starry Positive or Negative? Case 20: New Frontiers in Pathology 2010

  15. Differential Diagnosis, cont’d • Inflammatory Myofibroblastic Tumor • Indolent spindle-cell proliferation • Resembles malignant mesenchymal neoplasms • Benign or recurs locally • Described in lung, mesentery, omentum, retroperitoneum • ALK (anaplastic lymphoma tyrosine kinase) translocation 2p23 • 40-100% expressed by IHC Case 20: New Frontiers in Pathology 2010

  16. Inflammatory Myofibroblastic Tumor of the Uterus • IMT of the Uterus • N=6 • Size range: 1-12 centimeters • 3-polypoid growth of LUS • 3-bulky myometrial masses • Infiltration of endometrium, parametrium or cervical stroma • Fascicular, hypocellular, or hyalinized patterns • Lymphoplasmacytic infiltrate in all tumors • 100% expression of ALK (cytoplasmic pattern) • Laskin et al Am J SurgPathol 2005;29:1348-1355. Case 20: New Frontiers in Pathology 2010

  17. IMT (prolapsed fibroid) vs. Case 20 Intracavitary “fibroid” prolapsedthrough cervix Case 20: LEEP of cervix, no mass Case 20: New Frontiers in Pathology 2010

  18. IMT (prolapsed fibroid) vs. Case 20 IMT Example:ALK-1 Cytoplasmic Staining Pattern Case 20: ALK-1 negative staining Case 20: New Frontiers in Pathology 2010

  19. If it’s not IMT, then what? • Another test was ordered… • IHC Specific for Treponema pallidum • W-S (Steiner) always difficult to interpret • …why not? Case 20: New Frontiers in Pathology 2010

  20. IHC for spirochetal organisms (T. pallidum) Case 20: New Frontiers in Pathology 2010

  21. IHC for spirochetal organisms (T. pallidum) Case 20: New Frontiers in Pathology 2010

  22. IHC for spirochetal organisms (T. pallidum) Case 20: New Frontiers in Pathology 2010

  23. IHC for spirochetal organisms (T. pallidum) Case 20: New Frontiers in Pathology 2010

  24. Diagnosis: Cervix, LEEP: Inflammatory and reactive changes associated with underlying spirochetal infection, presumably Treponema pallidum. Clinical correlation required. Case 20: New Frontiers in Pathology 2010

  25. Case 20: Follow-up • Patient was successfully located and admitted to the local hospital • RPR, FTA-abs confirmed diagnosis of Syphilis • lumbar puncture • to rule out neurosyphilis… remember the schizophrenia? • No WBC’s, VDRL – negative. • Penicillin G, 2.4 million units IM given… then, • Patient signed out against medical advice Long term update: she did return to her PCP. RPR negative. Cervical biopsies, NO Spirochetes Case 20: New Frontiers in Pathology 2010

  26. John A. Fordyce, M.D.Professor of Dermatology and SyphilologyColumbia University • “It may be said that in general the features of the pathological anatomy of syphilis are the same wherever encountered in the body, subject only to modifications by the tissue affected, namely, a granuloma having its origin in the perivascular lymphatic spaces.” • Presented at the 39th Annual Meeting of the American Dermatological Association, May 1915 Case 20: New Frontiers in Pathology 2010

  27. 20th Century Trends in Syphilis Mortality JAMA. 1999;281:61-66. Case 20: New Frontiers in Pathology 2010

  28. Cases of P&S syphilis by sex during 1996-2002 in the six U.S. cities with the highest burden of infection in 2002 Case 20: New Frontiers in Pathology 2010

  29. Key Clinical & Pathological Features Stages Key Histology • Primary(10-90 days) • chancre, painless ulcer • Secondary (2-10 weeks) • rash on palms of hands and bottoms of feet • condyloma lata • Latent (2-30 years) • quiet, but infectious • Tertiary(years…) • i.e. Neurosyphilis • any organ system • swelling of capillary endothelium, resulting in narrowed or occluded small caliber vessels • vessels sheathed by lymphs and plasma cells • epidermal ulceration is followed by hypertrophy then hyperplasia, usually at the site of initial infection • giant cells are more common with increasing duration of infection • Gumma: • endarteritis, panarteritis, and destructive granuloma formation Case 20: New Frontiers in Pathology 2010

  30. 2008 Case 20: New Frontiers in Pathology 2010

  31. Case 20 Primary, Secondaryor Latent? Case 20: New Frontiers in Pathology 2010

  32. Syphilitic CervicitisObstet Gynecol 52(1S):12-14, 1978 • 23-year-old female diagnosed with “Stage III cervical sarcoma” • She received one dose of radiation therapy prior to the discovery of a strongly positive VDRL (1:32 dilution) • following an intramuscular injection of penicillin, clinical examination three months later revealed complete resolution of her cervical lesion • Syphilis and cervical malignancy • Early literature often discusses co-diagnosis Case 20: New Frontiers in Pathology 2010

  33. Case 20: A case of syphilitic cervicitis • Once ubiquitous, now relatively uncommon syphilis remains a “great imitator” • Keep syphilis infection on your radar… if you think about it, rule it out. Case 20: New Frontiers in Pathology 2010

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