Chloroma (Granulocytic Sarcoma / Myeloid Sarcoma)

Definition and Nomenclature

• Andrews' Diseases of the Skin, p. 3099
• Henry's Clinical Diagnosis and Management by Laboratory Methods

Associated Conditions (Four Clinical Settings)

1. Known AML - the most common association; occurs in ~3% of patients with myelogenous leukemia
2. CML or MDS - as a harbinger of an impending blast crisis
3. De novo presentation - in a previously undiagnosed patient, as the first sign of AML
4. Post-bone marrow transplantation (BMT) - as the initial sign of relapse

• Andrews' Diseases of the Skin, p. 3097
• Henry's Clinical Diagnosis and Management by Laboratory Methods

Epidemiology

• Incidence: 2.5-9.1% of AML cases on imaging series
• Orbital myeloid sarcoma in children typically presents around age 7 years
• AML overall has a median age of 65 years, but chloromas can occur at any age

Sites of Involvement

• Cummings Otolaryngology Head and Neck Surgery
• Kanski's Clinical Ophthalmology, p. 6782
• Grainger & Allison's Diagnostic Radiology

Skin Lesions

• Red, mahogany, or violaceous firm nodules
• Predilection for the face, scalp, and trunk
• May be solitary or multiple

Microscopy and Pathology

• Myeloblasts have more nuclear complexity and more cytoplasm (with granules and vacuoles) compared to lymphoblasts
• Auer rods - pathognomonic needle-like cytoplasmic inclusions; the only specific morphologic finding in AML
• Sheets of immature cells infiltrating extramedullary tissue

Diagnostic Pitfalls

• Non-Hodgkin lymphoma (most common error)
• Amelanotic melanoma
• Undifferentiated carcinoma

Immunophenotyping

• Anti-MPO (myeloperoxidase) - granulocytic lineage
• CD68 - monocytic lineage
• HLA-DR - positive in most AML subtypes (exception: acute promyelocytic leukemia/APL is HLA-DR negative)
• CD13, CD33 - myeloid markers
• CD19 - typically negative (anomalous expression in AML with t(8;21))

Radiology (MRI Features)

• Chloroma manifests as an extra-osseous mass:
  • Isointense to muscle on T1-weighted sequences
  • Hyperintense to muscle on PD-weighted / T2-weighted sequences
  • Avid enhancement following contrast administration
• Most common skeletal locations in children: skull, spine, ribs, sternum
• Pattern can mimic Ewing sarcoma (diffuse, permeative bone destruction)
• FDG-PET shows focal/diffuse increased uptake
• Grainger & Allison's Diagnostic Radiology

CML Blast Crisis Context

• 20% blasts in blood or marrow, OR

• A tissue infiltrate of blasts (chloroma), OR
• Prominent focal accumulation of blasts in the marrow biopsy
• Quick Compendium of Clinical Pathology, 5th ed.

Management

• Local irradiation for symptomatic/localized disease
• Systemic chemotherapy as for AML (the diagnosis of a chloroma is considered equivalent to AML)
• Bone marrow transplantation is the definitive treatment for eligible patients
• Marrow involvement usually follows if not already antecedent - patients with de novo chloroma must be treated systemically

Recent Evidence

Gallbladder Mass - FNAC Features

Background

• Grainger & Allison's Diagnostic Radiology
• Schwartz's Principles of Surgery, 11th ed.

Gross Pathology (for context)

FNAC Diagram

FNAC Cytological Features by Histological Subtype

1. Well-Differentiated Adenocarcinoma (Most Common)

2. Moderately Differentiated Adenocarcinoma

• Cell clusters with some acinar formation plus scattered isolated malignant cells
• Nuclear pleomorphism moderate to marked
• Focal tumor necrosis present
• Tumor giant cells may appear
• Intracellular and extracellular mucin seen
• Background: dirty with necrosis and inflammatory exudate ("tumor diathesis")

3. Poorly Differentiated Adenocarcinoma

• Predominantly dyscohesive (dissociated) tumor cells - few clusters/acini
• Abundant necrosis and inflammatory exudate in background
• Many tumor giant cells
• High N:C ratio with moderate to marked nuclear pleomorphism
• Multiple prominent nucleoli
• Stippled (salt-and-pepper) chromatin
• Few or no mucin-containing fragments

FNAC Features by Histological Type (WHO Classification)

Key Diagnostic FNAC Features - Summary

MALIGNANT GALLBLADDER MASS ON FNAC:

1. CELLULARITY
   └── Usually high (moderately to highly cellular smear)

2. ARCHITECTURAL PATTERNS
   ├── Acinar / glandular arrangements (most specific)
   ├── Papillary clusters (papillary subtype)
   ├── Sheets and irregular clusters
   └── Dyscohesive single cells (poorly diff.)

3. NUCLEAR FEATURES (MALIGNANCY CRITERIA)
   ├── Nuclear enlargement + pleomorphism
   ├── Coarse/clumped or stippled chromatin
   ├── Prominent macronucleoli (single or multiple)
   ├── Irregular nuclear membrane
   ├── High N:C ratio
   └── Nuclear molding (small cell type)

4. CYTOPLASMIC FEATURES
   ├── Intracytoplasmic mucin vacuoles
   └── Signet ring cells (mucinous/signet ring type)

5. BACKGROUND
   ├── Extracellular mucin
   ├── Necrotic / dirty background (tumor diathesis)
   ├── Inflammatory exudate
   └── Tumor giant cells (poorly diff.)

FNAC Procedure Notes

• Needle size: 22G for cytology; 18G for histological core
• Guidance: US-guided (most common), CT-guided, or EUS-guided (preferred if resectable candidate - lower seeding risk)
• Sensitivity: ~62% for extrahepatic bile duct tumors; higher (~96.8%) for gallbladder mass in dedicated series
• Complication rate: <0.2% overall (bleeding, bile leak, pancreatitis, infection each <0.08%)
• Needle track seeding: ~0.05% - therefore percutaneous biopsy is avoided if surgical resection is planned; EUS-FNA preferred in such cases
• Biliary brushings: ~55% sensitivity; helpful if positive

Differential Diagnosis on FNAC

Immunocytochemistry (IHC) Profile

• CK7+, CK19+ (biliary type)
• CK20 - variable
• CEA - positive
• CA 19-9 - positive
• EMA - positive
• Negative for: HepPar-1, CD56 (except NE tumors), S100