Dhanpat JainYale University School of Medicine, New

Haven, CT

Clinical history

59‐year‐old African American man CLL  Pain in the right  hand for 2‐3 weeks  Persistent fever with chills and night sweats for 6 months  Weight loss of 50‐Lbs

CT scan/MRI showed numerous mass lesions in the liver (seen better on PET scan

Labs show AST‐20u/L, ALT ‐20u/L, Alk phos112 u/L 

Differential diagnosis

Spindle cell neoplasm with inflammatory cells Leiomyosarcoma GIST Inflammatory myofibroblastic tumor Angiomyolipoma

Spindle cell carcinoma Primary (HCC, CC, or mixed tumor) Metastatic

Differential diagnosis

Infectious etiology Bacterial abscess  Fungal Syphilis 

IgG4 associated liver disease Inflammatory pseudotumor

Inflammtory MyofibroblasticTumor: Plasma cell granuloma, inflammatory

Mostly children and young adults (mean 10Y) Tumor of soft tissues and viscera, rare in liver Some (1/3rd) presentation with systemic symptoms

mimicking infection Fever, wt loss, anemia, thrombocytosis, ESR, Ig (polyclonal)

Histology: Spindle cells admixed with sprinkling of inflammatory cell, especially plasma cells

IHC: 2/3rd positivity for anaplastic leukemia kinase (ALK) Molecular diagnostics: Clonal cytogenetic rearrangement of ALK on chromosome 2p23 in

mostly pediatric cases Subset has clonal rearrangement of HMGIC gene on chromosome 12

Prognosis Recurrence in 25% Metastasis in 5%

HMB45

Differential diagnosis

Spindle cell neoplasm with inflammatory cells SMA, desmin, ALK, DOG1, CD34, CD31,  S100, HMB45, MelanA, Vimentin, CD68, Pan cytokeratin, EMA,  

Not a good fit for most sarcomas and Spindle cell carcinoma

Infectious etiology Grocott, AFB, Warthin‐Starry, B&B,  Fever and chills (6 months) but no localizing signs or no symptoms of infection

IgG4: Not done! Inflammatory pseudo‐tumor (“plasma cell granuloma”)

? Sampling error

Biopsy was repeated 2 more times Same findings and diagnosis About to be called Inflammatory Pseudo‐tumor for the 3rd time

RPR test for Syphilis was positive Treponema IHC: Strongly positive on all 3 biopsies

Repeat Warthin‐Starry stains: Negative 

“In reality, it appears that venereal syphilis was theby-product of two different populations meeting andexchanging a pathogen. It was an adaptive event,the natural selection of a disease, independent ofmorality or blame.”Carol Clark. Anthropologist, Emory University, Dec 2011

Syphilis: Incidence and demographics  

With HIV emergence: STD declined  With control of HIV: STD increasing CDC: 56, 471 cases reported in MSM (75%) Younger individual (20‐29Y) Higher incidence in African Americans, Hispanics and other ethnic minorities Often asst. with HIV and high risk sexual behaviors

Natural history and clinical features Primary Syphilis: Ulcer at the site of inoculation Chancre

Secondary Syphilis: dissemination weeks to months after exposure Maculopapular rash on palms and soles Lymphadenopathy Systemic symptoms

Tertiary Syphilis Gummatous syphilis Cardiovascular and/or neurosyphilis

Syphilis: Lab diagnosis Serologic diagnosis: Non‐treponemal tests (RPR, VDRL, TRUST)▪ Cheaper, rapid, easily available and easy to perform▪ Titers useful for response to treatment

Treponemal tests (FTA‐ABS,  MHA‐TP, TP‐PA)▪ Specific▪ Remain reactive even after treatment

Demonstration of organisms in tissues▪ Smears: Dark field illumination/ DFA‐TP▪ IHC: Monoclonal/polyclonal antibody ▪ Silver Stain: Warthin‐starry, Steiner, Dieterle▪ PCR based assays

Secondary syphilis: a histologic and immunohistochemicalevaluationMai P. Hoang, WhitneyA.High and Kyle H. Molberg. J Cutaneous pathology; 2004.

Skin biopsies 17 patients (19 biopsies) IHC (monoclonal Treponema antibody): 71% sensitivity

Silver Stain: 41% sensitivity

Hepatic Syphilis

Occurs during secondary or tertiary stage 6‐10% of untreated patients (30‐40% in HIV patients)

Transmission reported with infected  transplanted solid organs

Disproportionate Alk Phos elevations Liver Bx: Often not required Non‐specific chronic hepatitis Plasma cell rich/Neutrophil rich/ histiocyte rich Peliosis

Treatment

Parenteral injection of Benzathine penicillin G is the treatment of choice

Modified treatment required for Patients allergic to penicillin Secondary/tertiary syphilis Immunosuppressed individuals

The great mimic

Any other questions??