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外科病理討論會2010 年 2 月 26 日 (Friday) 7:30 AM

地點：萬芳醫院五樓階梯教室同步視訊：附醫第三大樓 11 樓會議室、

雙和醫院行政大樓三樓第一會議室 主持人：方嘉郎 醫師

病理號碼 姓 名 年齡 性別 Clinical DiagnosisChart

Number科別 醫師

WF09-12136 WF09-12145

劉 x 諺 27 男 R/O Brain tumor 10278929 神經外科 林乾閔醫師林欣穎醫師

WF05-05895 WF07-05614 WF07-11901 WF09-09993

陳 x 雲 54 女 Recurrent vaginal polypoid tumor

03449864 婦產科 許淳森副院長祝怡麟醫師

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Patient Profile

• Name: 劉 X 諺• Age: 27-year-old• Gender: Male• Chart No.: 10278929

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Chief Complaint

• Right side weakness and numbness for 3 weeks

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Brief History• AIDS

– 2007/11• Lamivudine, abacavir, atazanavir

– 2009/5• HIV viral load < 40 RNA copies

• CD4 count 399/L

– Cryptococcus meningitis • 2007/11-2008/2

– Amphoterincin B and fluconazle• 2008/2-2008/5

– Oral fluconazle

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Brief History

• 2009/11/2 NTUH– Right side weakness (muscle power 4+ ) for 2 weeks

– Lumbar puncture• High opening pressure

• Increased protein level

• Indian ink: Negative

– Biopsy frame broken Transfer to our hospital

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Crytococcal Ag 1:64x(POSITIVE)Toxoplasma IgG Ab (IU/ml ) 0.14(NEGATIVE)Toxoplasma IgG Ab (IU/ml ) 0.14(NEGATIVE)Toxoplasma IgG Ab (IU/ml ) 0.14(NEGATIVE)Toxoplasma IgM (index ) 0.143(NEGATIVE)

Serologic Data

• 11/13 Blood

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After Admission

• 11/13– Dexamethason 5mg q8h iv for one week

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HIV (log) [HIV病毒量 病毒(log)] (log copy/ml )量 <1.6 0~1.60

HIV viral load test [HIV病] (copy/mL )毒負荷量檢查 <40 0~40

HIV Viral Load

• 11/23 Blood

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檢驗項目 檢驗結果值 參考值CD4 [] (% ) 9.8 23.2~53.2

CD4/CD8 Ratio [] (ratio ) 0.38 0.59~2.24

CD4 Absolute Count [](cells/μ L ) 95 0~0

CD8 [] (% ) 25.6 18.7~48.6

CD8 Absolute Count [](cells/μ L ) 248 0~0

Immunology Study

• 11/23 Blood

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Treatment Course

– 12/8 –12/16• Fluconazole 600mg iv qd

• Flucytosine 2000mg po tid

– 12/16 • Amphterincin B

• Flucytosine

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檢驗項目 檢驗結果值Cryptococcus Ag [] (2X(+))

India stain [] (NEGATIVE)

Appearance [外觀] (CLEAR)

Color [] (COLORLESS)

Lymphocyte [淋巴球](% ) 92

Polymorphonuclear cell

[多形性核白血球] (% ) 8

Protein(Pandy's) [蛋白質] (NEGATIVE)

RBC [紅血球] (/ul ) 89

WBC count [白血球計數] (/ul ) 2

Lab Data of CSF

• 12/16 CSF– Opening pressure: 12 cmH2O

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檢驗結果值 參考值GLU [腦脊液葡萄糖] (mg/dl ) 59 40~75

TP [腦脊液全蛋白](mg/dl ) 98.6 15~45

Lactic acid [乳酸](mmol/l ) 1.4 0~2.8

Lab Data of CSF

• 12/16 CSF

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T1W and T2W FLAIR

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DWI and Enhanced T1W

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MR Spectroscopy

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T2W and Enhanced T1W

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MRI Findings

• Ring enhancing nodule at midbrain (low on T1W, high on T2W, low on DWI, thick wall with enhancement)

• Faint enhancing nodules at bilateral basal ganglia

• Faint leptomeningeal enhancement• Mild hydrocephalus

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Ring-Enhancing Lesions• Metastases• Abscess, including pyogenic abscess and abscess caused by at

ypical organisms, such as bacterial pathogens (Mycobacteria, Nocardia, Actinomyces, Rhodococcus, and Listeria); fungal pathogens (zygomycosis, Histoplasma, Coccidioides, Aspergillus, and Cryptococcus); and parasitic pathogens (neurocystircercosis, Echinococcus, and Entamoeba)

• Glioma and other primary CNS neoplasms (eg, lymphoma)• Infarction• Contusion• Demyelination (multiple sclerosis, acute disseminated enceph

alomyelitis)• Resolving hematoma/radionecrosis

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MRI Findings of Cryptococcus

• Dilated Virchow-Robin Space• Hydrocephalus• Miliary leptomeningeal or parenchymal enhanc

ing nodules• Faint leptomeningeal enhancement• Pseudocyst• Cryptococcoma

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2009/11/2 2009/11/20

2010/1/182009/12/18

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PASPAS

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Pathological Diagnosis

• Brain, cerebrum, midbrain and right basal ganglion, stereotactic biopsy, cryptococcosis, HIV-associated

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Cryptococcal Meningoencephalitis

• Most common fungal infection of the central nervous system

• 6% to 8% of AIDS patients

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Pathology of Cryptococcal Meningoencephalitis:Analysis of 27 Patients with Pathogenetic Implications

Lee SC et al, Hum Pathol 1996; 27:839-47.• A pathological analysis in 27 patients in autopsy file at the Albert Eins

tein College of Medicine in New York, from 1966 to 1994

• 13 cases of HIV-associated, male predominance

• Most often in the basal ganglia, midbrain, and superficial cerebral cortex

• Mixed perivascular and parenchymal distribution

• Intracerebral collections of cryptococcal yeasts produced macroscopic “soap-bubble lesion”

• In HIV-associated patients, not associated with a significant inflammatory response

• Large cryptococcomas with numerous organisms were common in HIV-associated patients

• Prominent (or exclusive) encephalitic in AIDS patients

• In some cases, multiple ring-enhancing lesions on radiographs simulating toxoplasmosis

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Immune Reconstitution Syndrome

• Immune reconstitution after HAART in HIV-infected patients may cause undesirable effects, the so-called paradoxical reaction

• As a result of restored immunity, HIV-infected patients receiving HAART may experience atypical clinical manifestations of cryptococcosis, as well as other opportunistic disorders

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Immune Reconstitution Syndrome- Pathogenesis

1. An inflammatory reaction that unmasks active infection,

such as mycobacteria, cytomegalovirus, or cryptococcus

– Unclear pathogenesis

– Increase in the specific lymphocyte response against microbial antigens

2. A paradoxical reaction to latent antigens of inactive

infectious agents. The pathogens are supposed to be dead

or replicate at a very low level .

– Opportunistic agent can not be identified by cultures, but only revealed on special histological specimen

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Immune Reconstitution Cryptococcosis

• HAART era: significant clinical and laboratory changes of HIV-related cryptococcosis• Rapid immune recovery following HAART: varied presentations of AIDS-related opportunism• A retrospective cohort analysis of 84 patients with AIDS-related cryptococcal meningitis: 18 out of 59 (30.5%) patients who started HAART following treatment developed IRIS• Risk factors for the development of IRIS following cryptococcal infection: Early initiation of antiretroviral therapy Fungemia A low initial CD4 count

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Case 2

• Name: 陳 XX• Age: 52 years old• Gender: Female• Chart Number: 03449864• G2P2, NSD• Menopause without hormone therapy (HT)

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Clinical Course 1/8

• Irregular vaginal spotting that had lasted for 2 months on July 1, 2005

• Pelvic examination: a cul-de-sac induration was noted

• Transvaginal ultrasonography revealed a normal uterus and adnexa

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Uterus-sagittal view

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Uterus-transverse view

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• Histological analysis of the cervical biopsy suggested adenomyomatous polyp suspected originate from prior endometriosis

• Routine hematological, biochemical determinations revealed no particular abnormalities except elevated CA-125 (46 U/mL)

Clinical Course 2/8

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• She was referred for pelvic MRI examination• Focal bulging space taking lesion at posterior lip

of lower body of uterus and extended to cervix, with slightly heterogeneous enhancement

Clinical Course 3/8

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Clinical Course 4/8

• Pelvic examination revealed vaginal recurrent adenomatous polyp, r/o sarcoma on June 1, 2007

• Transvaginal ultrasonography revealed two small cervical mass

• Pelvic MRI was arranged again and showed soft tissue at posterior aspect of lower uterus and cervix with slightly heterogeneous enhancement

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Uterus-sagittal view

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Uterus-transverse view

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Ultrasound Findings

Uterus: Position: AVF

size: 56.8 x 37.1 x 40.6 mm

endometrium: thickness 3.6 mm

two small masses were seen in the cervix on scan

mass: (1) 17.5 x 15.5 mm

(2) 16.7 x 10.9 mm

Blood Flow:

S/D: 2.56; RI: 0.61; PI: 1.06

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Clinical Course 5/8

• Vaginal polypoid excision was performed• Pathology report revealed adenofibroma

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Clinical Course 6/8

• 3rd pelvic MRI was performed• R/O endometriosis or true mass lesion with subs

erosa is located at uterus,cervix or vagina• Laparotomy was performed under the impressio

n of persistent recurrent adenofibroma

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Clinical Course 7/8

• During operation, a normal-sized uterus with severe pelvic adhesion were found, then total hysterectomy with bilateral salpingoophorectomy was performed

• A well-defined protruding whitish nodule around 4 x 3 cm. at the posterior lip of cervix

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Clinical Course 7/8

• 4th pelvic MRI was performed due to vaginal polypoid tumor recurrent

• Soft tissue mass about 3.3x3.8x4.5cm from residues vagina stump, compatible with recurrent adenofibroma

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Clinical Course 8/8

• Vaginal polypoid biopsy was performed• Pathology report revealed atypical spindle cell

proliferation

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2005/7/11

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2005/7/11

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2005/7/11

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2005/7/11

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2007/6/28

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2007/11/2

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2009/10/05

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2009/10/05

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2009/10/05

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2009/10/05

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2009/10/05

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Image Findings

• Mass lesion at vaginal stump• Low SI on T1W, high SI on T2W,

heterogeneous enhancement at post contrast T1W

• According the clinical course, recurrent tumor is considered

• Pathology benign, behavior malignant

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VimentinVimentin

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ActinActin

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CD10CD10

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Ki-67Ki-67

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Immunohistochemical Study

• Vimentin (+)• CD10: focal (+) • Actin: focal (+)• Ki-67 labeling index:

< 5%

• Desmin (-)• Myoglobulin (-)• CK (-)• ER (-)• PR (-)

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Pathological Findings• Low to moderate cellularity of spindle and oval

tumor cells in fascicles and whorls• Minimal to mild cytological atypia of tumor cell

s• Rare mitotic figure (< 1/10 HPF)• Mixed benign endometrial glands• Associated with endometriosis• Recurrent adenofibroma, cervicovaginal region,

arising from endometriosis

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Adenofibroma• A neoplasm composed of benign epithelial and

mesenchymal components• Polypoid lesion with fibrous consistency and dil

ated cystic spaces• Benign endometrial-like type glands admixed w

ith fibroblastic type, endometrial stromal, or smooth muscle mesenchymal components

• Absence of cytological atypia or mitotic activity

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Differential Diagnosis• Adenosarcoma

– Biphasic low-grade neoplasm with benign epithelial component and a sarcomatous mesenchymal component

– Mitotic count 2/10 HPF– Marked stromal cellularity with periglandular cuffi

ng and/or more than mild stromal atypia

• Sarcoma botryoides• Endometrial stromal tumor

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CD10CD10

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ActinActin

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Ki-67 LI: < 5%Ki-67 LI: < 5% Ki-67 LI: 20%Ki-67 LI: 20%

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Adenosarcoma- Diagnostic Criteria - Clement and Scully

1. characteristic relationship between the sarcomatous component and at least some of the glands, with formation of periglandular cuffs and intraglandular protrusions of cellular stroma2. noninvasive glands lined by benign-appearing mullerian epithelia of various types showing mild to marked nuclear atypia3. an average of >=2 mitosis/10 HPF in the stromal component4. more than mild nuclear atypia of the stromal cells

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Mullerian AdenosarcomaA Clinicopathologic and Immunohistochemical Study

of 55 Cases- Challenging the Existence of adenofibroma Gallardo A et al, Am J Surg Pathol 2009; 33:278-88

• Local recurrence of typical adenofibromas with myometrial and vascular invasion has been described

• Forty-eight uterine tumors (37 of the corpus and 11 of the cervix), 4 ovarian tumors, and 1 each tumors of the vagina, fallopian tube, and peritoneum in this series

• Clinically malignant uterine tumors with moderate stromal cellularity, focal periglandular cuffs, low mitotic count (<2 MF/10HPF), and mild nuclear atypia

– ? whether or not adenofibroma exists as a tumor entity

• No evidence that there exist histopathologic criteria that will reliably distinguish adenofibroma from adenosarcoma

• Some tumors currently classified as adenofibromas, on the basis of their low mitotic count and lack of significant nuclear atypia, are, in fact, well-differentiated adenosarcomas

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Mullerian adenosarcoma of vagina arising in persistent endometriosis: Report of a case and

review of the literature Liu L et al, Gynecol Oncol 2003; 90:486-90

• There are only two prior case reports in the English literature of a primary mullerian adenosarcoma arising in vaginal endometriosis

• Persistent extrauterine endometriosis even after surgical and hormonal treatment may undergo malignant transformation of the stroma into an adenosarcoma

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Pathological Diagnosis

• Recurrent adeofibroma, cervicovaginal region, with sarcomatous transformation

• ? Adenosarcoma– Low-grade sarcoma – High recurrence rate: 25-40%– Recurrence sites: typically in pelvis or vagina– Distant metastasis: 5%