Pediatric Hemato-Oncology Interhospital Conference
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1 Pediatric Hemato-Oncology Interhospital Conference Pallapa Bunjerdluk Division of Hemato-Oncology, Department of Pediatrics, Faculty of Medicine, Prince of Songkla University 19-Dec-2017
2 Patient profile เด กชายไทย อาย 14 ป ภ ม ลาเนา จ.พ ทล ง Chief complaint: ม แผลเจ บท ปากเป นมา 2 เด อน
3 Present illness 2 เด อนก อนมารพ.ม แผลในปาก เจ บ ม เล อดออกซ มๆ แผลเป นเองโดยไม ได ม อ บ ต เหต ใดๆ แผลเป นป นส ขาว ท กระพ งแก ม ล น ทานอาหารได ลดลง ไม ม ต มน าท ผ วหน ง ส วนอ น ร ส กม ไข ต าๆ ตาแดงเล กน อยม ข ตาไม มาก รพช.ให การว น จฉ ยว า oropharyngeal stomatitis ได ยา Acyclovir(200) 1x5 เป นเวลา 5 ว น อาการด ข น แผลย งไม หายสน ทแต เจ บด ข น แพทย จ งให กล บบ าน
4 1 เด อนก อนมารพ. แผลในปากย งม เท าๆ เด ม และเร มม แผลท ร มฝ ปาก เพ มข น รพช.ส งต อรพ.จ งหว ดให การว น จฉ ยว า herpetic gingivostomatitis with secondary bacterial infection ให การร กษาด วย augmentin 500 mg IV q 12 hr 7 ว น หล งจากน นอาการแผลด ข นแต ก ไม ได หายสน ท แพทย จ งให กล บบ าน 1 ส ปดาห ก อนมารพ.แผลท ปากเป นมากข น ม อาการตาแดงเพ มข น ตามต วม ต มน าข นและแตก ทางรพ.จ งหว ดจ งส งต วมารพ.มอ.
5 ซ กประว ต เพ มเต ม
6 ประว ต เพ มเต ม Birth history: บ ตรคนท 3/3, C/S due to post-term, Birth weight 3,500 gm, no complication ไม ม โรคประจ าต วแข งแรงด มาตลอด ไม ม แพ ยาอาหาร ม น าหน กลด 7 ก โลกร มใน 2 เด อน อาศ ยอย บ านค ณป าท ม ส ขภาพด
7 Physical examination GA: active child V/S: BT 36.9 O C, PR 111/min, RR 24/min, BP 110/65 mmhg Measurement: BW 38.4 kg[p10-25], Ht cm[p50-75] HEENT: -not pale, no icteric sclera, bilateral mild injected bulbar conjunctiva -oral painful erosions with hemorrhagic crusting and gray dirty patch at buccal mucosa, tongue and lips Heart: normal S1S2, no murmur Lungs: mild suprasternal retraction, normal chest contour, clear breath sound both lungs
8 Abdomen: soft, no palpable mass, liver and spleen can t be palpated Genitalia: normal size testes, no mass, no lesion Lymph node: no significant all groups Ext: no lesion Neurological examination: grossly intact Skin: generalized, painful, erythematous papule, vesicle, bullae, erosive and target lesions at forehead and trunk
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14 Problem list
15 Problem list Painful erosion in oral cavity and lips Bilateral injected conjunctiva Generalized vesiculobullous at chest wall and back Significant weight loss Suprasternal retraction
16 Differential diagnosis 1 Ans
17 Differential diagnosis Autoimmune disorder:pemphigus vulgaris, rheumatoid arthritis, myasthenia gravis Infectious disease: virus(herpes virus: HHV-8, acute herpetic stomatitis ), bacteria(impetigo, SSSS), fungus(candidiasis), TB Paraneoplastic pemphigus: Occult Non-Hodgkin lymphoma, Castleman s disease Drug reaction: SJS, TEN, EM
18 Investigations A B C D E F G H I J K M Ans Df
19 Pathologic diagnosis Skin at chest wall Eosinophilic spongiosis Suprabasal separation with acantholytic cells, eosinophils and lymphohistiocytes. Slight infiltration of lymphohistiocytes, neutrophils and eosinophils in the dermis No malignant cell involvement, Tdt negative Immunofluorescence study: Positive 2+ of IgG, C3 at intercellular space Negative of IgA, IgM and C1q Pic
20 Skin pathology
21 Skin pathology L
22 Skin pathology IgG C3
23 Infectious work up PPD test: 0 mm Anti HIV screening test: non reactive Tzanck smear vesicle: negative multinucleated giant cell HHV type 1-6 by PCR: not detected Hemoculture: no growth Sputum: negative for TB by PCR Tissue culture for TB, Fungus- negative L
24 Autoimmune disease work up CH50: 85% [ref 90-94] ANA by IFA: positive mix pattern(homogeneous, speckle, nucleolar) titer 1:320 [ref: negative titer <1:80] Anti ds-dna by IFA: negative Rheumatoid factor: negative <20 IU/mL Anti Sm (ELISA): negative L
25 Dermatoimmunology Indirect immunofluorescence(iif) Negative for rat bladder substrate Negative for circulating IgG anti-intercellular antibody using human skin substrate Anti-desmoglein 1 antibody, ELISA: U/mL (0-20): positive Anti-desmoglein 3 antibody, ELISA: U/mL (0-20): positive Imp: positive anti-dsg 1 and 3 by ELISA L
26 Complete blood count WBC 8,330 /µl, PMN 50%, Lymph 46%, Eo 4% Hb 14 g/dl, Hct 42%, RBC 5.15x10 6 /µl, MCV 81.4 fl, MCH 27.2 pg, MCHC 33.4 g/dl, RDW 12.8% Plt 330,000/µL Retic 1.32% L
27 Blood chemistry BUN 9.9 mg%, Cr 0.72 mg% Na mmol/l, K 4.26 mmol/l, Cl 96.9 mmol/l, HCO 3 25 mmol/l Ca 9.5 mg%, Phos 4.0 mg% Uric 3.3 mg% DB 0.25 mg%, TB 0.64 mg%, SGOT 28 U/L, SGPT 21 U/L, ALP 203 U/L, TP 8.6 g%, Alb 4.0 g%, GLOB 4.6 g% L
28 Pathologic diagnosis Anterior mediastinal mass, needle biopsy Positive for CD3, CD4, CD8, CD10, Tdt, CD99 Negative for CD20, EMA, AE1/AE3, CK19, P63, CD15, CD30 No granulomatous formation Imp: T lymphoblastic leukemia/lymphoma L
29 Pathologic diagnosis Clotted marrow: 40% cellularity Presence of all three lineages with maturation No clusters of blasts(cd34+ rare, Tdt+ few) Negative for malignancy Imp: Normal bone marrow study L
30 Tumor marker LDH 295 U/L AFP 0.74 ng/ml B-HCG < 1.00 miu/ml L
31 Chest X-ray 2
32 L
33 CT-chest A well-defined heterogeneous intense enhancing mass involving ant.and middle mediastinum size 8.9x6.4x7.4 cm Mass compression trachea, left shifting of trachea and posterior displacement of rt. main bronchus Mediastinal node size 1.2 cm No pulmonary mass, nodule or infiltration No bony destruction Imp: Anterior and middle mediastinum mass L
34 CT-abdomen No significant intraabdominal lymphadenopathy Prominent sized liver without focal mass Spleen, pancreas, both kidneys and urinary bladder are unremarkable Imp: Normal study L
35 Paraneoplastic pemphigus(pnp) T lymphoblastic lymphoma stage III
36 Vesiculobullous lesion Inherited disorder Acquired disorder 1.Bullous ichthyosiform erythroderma 2.Incontinentia pigmentti 3. Epidermolysis Bullosa EM: Erythema multiforme Infection Virus:HSV Bacteria,TB Candidiasis Bullous scabies Autoimmune disease Bullous pemphigoid Pemphigus vulgris/ foliaceus Paraneoplastic pemphigus Drug reaction SJS-TEN EM Indian J Pediatr 2015 ;82:805-8 Indian J Paediatr Dermatol 2015;16:9-16
37 Paraneoplastic pemphigus First described in 1990 Paraneoplastic autoimmune multiorgan syndrome or PAMS Rare, life-threatening immune-mediated bullous condition Characterized by the presence of Intractable painful stomatitis Cutaneous include palms,soles and nails: flaccid cutaneous bullae, erosion Ocular: irritation, pain, redness, worsening of vision and mucus discharge Clin Dermatol 2016;34: J Am Acad Dermatol 2017;77:
38 Diagnostic criteria: revised by Camisa and Helm, 1993 Major criteria: 1.Polymorphic mucocutaneous eruption 2.Concurrent internal neoplasia 3.Specific serum immunoprecipitation pattern Minor criteria: 1.Histologic evidence of acantholysis in biopsy specimen at least one site 2.DIF showing intercellular and basement membrane staining 3.IIF staining with rat bladder epithelium Three major OR Two major and two minor criteria Oral Oncol 2004;40:553-62
39 Paraneoplastic pemphigus Pathogenesis: - NOT Fully known! - Tumor(eg. B-cell lymphoma) produce autoantibodies directed against: desmosomal and hemidesmosomal antigens(periplakins and envoplakins) - Antitumor immune response cross-reacts with normal epithelial proteins - Epitope spreading: chronic inflammation leads to exposure of new self-antigen, triggering a humoral response - Failing of the antineoplastic immune surveillance caused by immunosuppressive therapy for pemphigus Pediatrics 2004;114:e513-6 Int J Dermatol 2001 ;40: Clin Dermatol 2013 ;31:
40 Approach to patient with paraneoplastic pemphigus Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K. Fitzpatrick's Dermatology in General Medicine, 8e; 2012
41 Paraneoplastic pemphigus Adult-lymphoma -89% B cell phenotype -11% T cell phenotype Children: -Castleman s disease -Sarcoma Acta Haematol 2014;132:73-74 Br J Dermatol 2015;173:
42 - 23 immunobullous-children in a referral population base of 4 million people over a 16-year period. - PNP: only one case - Castleman s disease Pediatr Dermatol 1997;14:
43 The largest pediatric case series: 14 children with PNP Severe oral mucositis and cutaneous lichenoid lesions Occult Castleman s disease Diagnostic marker: Serum autoantibodies against plakin proteins High mortality: pulmonary injury(bronchiolitis obliterans pneumonia) Br J Dermatol 2002;147:
44 The first report of PNP in a child, only one report A 7-yr-old boy with a T-cell lymphoblastic lymphoma stage IV Severe persistent erosive and crusting mucocutaneous eruption DIF: deposition of C3 in a linear pattern along the dermo-epidermal junction IIF staining with rat bladder epithelium Slow resolution of skin disease over a period of 4 weeks 11 months after initiation of CMT, he was in complete remission but continued to develop occasional isolated small oral erosions Br J Dermatol 1993 ;128:
45 Prognosis Very poor prognosis and high mortality rate Unfavorable: Non-Hodgkin lymphoma Favorable: Castleman disease and thymoma Overall survival rates: 49%, 41% and 38% at 1, 2 and 5-year Cause of death: bronchiolitis obliterans and infection. Poor factor: erythema multiforme-like skin lesions (High serum level of TNF, Fas ligand) Histologic keratinocyte necrosis Treatment of the underlying neoplasm: may improve PNP Br J Dermatol 2003;149: Arch Dermatol 2012;148:
46 Progression note After complete induction phase Improve skin lesion Persistent post inflammatory hyperpigmentation Persistent oral painful erosions Decreased size of anterior mediastinum mass 2 weeks after start induction
47 2 weeks after start induction
48 After HR-augmented consolidation phase II week 5
49 Thank you
Department of Dermatology, Nippon Medical School, 1-1-5, Sendagi, Bunkyo-ku, Tokyo , Japan 2
Dermatology Research and Practice Volume 2010, Article ID 931340, 5 pages doi:10.1155/2010/931340 Case Report Paraneoplastic Pemphigus Presenting as Mild Cutaneous Features of Pemphigus Foliaceus and Lichenoid
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