What is the clinical significance of a low‑back excision pathology report showing superficial and deep mixed lymphohistiocytic and eosinophilic inflammatory infiltrate?

Clinical Significance of Mixed Lymphohistiocytic and Eosinophilic Inflammatory Infiltrate in Low Back Excision

This pathology report describes a nonspecific inflammatory pattern that requires immediate clinical correlation to exclude histiocytic neoplasms (particularly Langerhans cell histiocytosis, Rosai-Dorfman disease, or Erdheim-Chester disease), cutaneous lymphoproliferative disorders, and reactive inflammatory processes.

Immediate Diagnostic Considerations

The presence of mixed lymphohistiocytic and eosinophilic infiltrate in superficial and deep tissue is not pathognomonic for any single entity and represents a pattern seen across multiple disease categories 1.

Primary Differential Diagnosis

Histiocytic Neoplasms:

• Langerhans cell histiocytosis (LCH) characteristically shows intermixed eosinophils that are commonly numerous, along with histiocytes displaying nuclear grooves 1, 2
• Rosai-Dorfman disease (RDD) demonstrates an inflammatory background with numerous plasma cells, lymphoid follicles, and neutrophilic infiltrates alongside histiocytes 1
• Cutaneous RDD presents as slow-growing, painless nodules or plaques and can occur as isolated cutaneous disease without lymphadenopathy 1

Cutaneous Lymphoproliferative Disorders:

• Lymphomatoid papulosis (LYP) Type A shows scattered CD30+ tumor cells intermingled with numerous inflammatory cells including small lymphocytes, neutrophils, eosinophils, and histiocytes 1
• This pattern can mimic reactive processes, making immunohistochemistry essential 1

Reactive/Inflammatory Processes:

• Drug-induced hypersensitivity reactions demonstrate marked mixed inflammatory cell infiltrates with neutrophils, lymphocytes, plasma cells, and eosinophils 1
• Inflammatory pseudotumor shows polymorphous reactive cellular infiltrate with lymphocytes, plasma cells, and histiocytes 3, 4, 5

Required Immediate Actions

Essential Immunohistochemical Panel

The pathology specimen must be stained with the following panel to establish a definitive diagnosis 1:

• CD163 or CD68 (histiocytic markers)
• S100, CD1a, and Langerin (CD207) (to identify LCH)
• Factor XIIIa (histiocytic differentiation)
• CD30 (to exclude lymphoproliferative disorders) 1
• IgG and IgG4 (to exclude IgG4-related disease) 1
• CD20 and light chains (to exclude B-cell lymphoma) 1

BRAF V600E mutation testing by immunohistochemistry or molecular methods is mandatory if histiocytic neoplasm is suspected, as this mutation is present in over 90% of LCH cases 2, 1.

Critical Clinical Correlation Required

Obtain the following clinical information immediately 1, 2:

Constitutional symptoms:

• Fever, night sweats, weight loss (suggest systemic histiocytic disease or lymphoproliferative disorder) 1
• Bone pain (60% of LCH patients have skeletal involvement) 2

Endocrine symptoms:

• Polyuria/polydipsia suggesting diabetes insipidus (present in 50-70% of LCH patients) 2, 1

Skin examination:

• Presence of other cutaneous lesions, papules, nodules, or plaques 1
• History of recurrent self-healing papulonodular lesions (suggests LYP) 1

Medication history:

• Recent initiation of immune checkpoint inhibitors or molecular targeted therapies (can cause drug-related inflammatory infiltrates with eosinophils) 1

Smoking history:

• Active smoking in context of respiratory symptoms (LCH has 50-60% pulmonary involvement in smokers) 2

Staging Evaluation if Histiocytic Neoplasm Confirmed

If immunohistochemistry confirms a histiocytic neoplasm, the following staging must be completed 2, 1:

• Full-body FDG PET-CT (preferred over technetium-99m bone scan for simultaneous bone and soft tissue evaluation) 2
• Brain MRI with gadolinium contrast (to evaluate CNS involvement) 2
• High-resolution chest CT (to assess pulmonary involvement) 2
• Complete blood count with differential (to identify concomitant myeloid neoplasm, present in 10% of histiocytic cases) 1, 2
• Comprehensive metabolic panel, LDH, and C-reactive protein 2
• Complete endocrine assessment: morning urine and serum osmolality, FSH/LH with sex hormones, corticotropin with morning cortisol, TSH and free T4, prolactin and IGF-1 2

Management Algorithm Based on Final Diagnosis

If Langerhans Cell Histiocytosis (CD1a+, Langerin+, S100+):

• Solitary cutaneous lesion: Observation or surgical excision with close surveillance 2
• Multisystem disease: Systemic therapy with consideration of BRAF inhibitors (vemurafenib) if BRAF V600E mutation present 2
• Long-term endocrine surveillance mandatory as diabetes insipidus can develop years after initial diagnosis 2

If Rosai-Dorfman Disease (S100+, CD68+, CD1a-):

• Isolated cutaneous disease: Often self-limited; observation or local excision 1
• Multisystem involvement: Prognosis correlates with number of extranodal systems involved 1

If Lymphoproliferative Disorder (CD30+):

• Lymphomatoid papulosis: Expectant management as lesions are self-healing 1
• Primary cutaneous ALCL: Complete surgical excision when feasible 1

If Reactive/Drug-Induced:

• Discontinue offending agent if drug-related 1
• Corticosteroids may be required for severe drug reactions 1

Critical Pitfalls to Avoid

Do not accept "nonspecific inflammation" as a final diagnosis without immunohistochemistry, as classic histopathologic features are not always present and may demonstrate only nonspecific inflammation and fibrosis 1.

Do not assume benign reactive process based solely on morphology, as the presence of large atypically appearing cells with inflammatory infiltrate is seen in both reactive and neoplastic conditions 1.

Ambiguous cases require re-evaluation at centers with histiocytosis expertise, particularly when histopathologic findings show atypical histiocytic infiltrates in the appropriate clinical context 2, 1.

Negative BRAF V600E immunohistochemistry should be confirmed with molecular testing (PCR or next-generation sequencing), as immunohistochemistry may have insufficient sensitivity 2.