Progressive nodular histiocytosis (PNH) is a rare condition characterized by progressive eruption of multiple yellowish-brown papules and nodules on the skin and mucous membranes. We present the case of a 37-year-old Caucasian man with gradually increased appearance of nodular lesions on the forehead and right temple. These lesions were initially diagnosed as xanthomas and did not respond to intralesional injections of triamcinolone. Additional biopsy revealed an intense dermal infiltrate of foamy mononuclear epithelioid cells with a minor admixture of plasma cells, lymphocytes, and scattered multinucleated giant cells. On immunohistochemical staining, the lesional cells were positive for CD163 and CD68 and negative for CD1a, thus confirming a mononuclear-macrophage lineage. The clinical presentation and the histological impression lead to the diagnosis of PNH. This condition could be challenging, mimicking microscopically similar lesions of the non-Langerhans cell histiocytosis group. Although uncommon, PNH stands out due to its clinical and microscopic features and should be taken into consideration in the differential diagnosis of cutaneous histiocytoses.
Progressive nodular histiocytosis (PNH) is a rare normolipemic cutaneous xanthogranulomatous disorder that belongs to the group of mucocutaneous non-Langerhans cell histiocytoses [
A 37-year-old Caucasian male presented with a history of multiple persistent lesions on his forehead and right temple. His past medical history was essentially noncontributory and included premature atrial contractions controlled with propafenone and escitalopram. His labs showed normal triglycerides and borderline elevated cholesterol (total 5.41 mmol/L; LDL 3.38 mmol/L).
The patient initially reported 2-3 lesions that gradually increased in number in the following months. All lesions looked identical and described as moderately painful pink violaceous papules and nodules with irregular borders (Figure
Clinical photograph showing multiple nodules on the patient’s forehead.
Histologic evaluation of the recurrent/persistent lesions revealed an intense dermal infiltrate of foamy tissue macrophages with a minor admixture of plasma cells, lymphocytes, and scattered multinucleated giant cells (see Figures
Micrograph of the forehead lesions demonstrating intense dermal-based infiltrate of foamy macrophages with sparing of skin adnexa. H&E ×40.
Higher-power view revealed predominantly foamy tissue macrophages with a minor admixture of plasma cells, lymphocytes, and scattered multinucleated giant cells. H&E ×100.
A close up of a different field shows a predominance of spindled cells with prominent extracellular collagen deposition.
CD163 immunohistochemical study highlights the tissue macrophages. ×100 magnification.
Since Taunton et al. described the first case of progressive nodular histiocytoma (subsequently renamed progressive nodular histiocytosis) in 1978 [
PNH most commonly affects young to middle-aged adults who present with nonpainful, nonpruritic, widely disseminated, randomly distributed red-brown cutaneous papules and nodules [
The superficial papules, deep nodules, and mucosal polyps of PNH span a histologic continuum. The superficial lesions show a diffuse infiltrate of foamy tissue macrophages. Fibrosis in the deeper lesions imparts a spindled appearance to the lesional cells, which are often arranged in a storiform pattern. Scattered multinucleated Touton giant cells and a modest infiltrate of lymphocytes and plasma cells are encountered in both types of lesions. The lesions of PNH may show focal infiltration of proximate structures like skeletal muscle, but nuclear/cytologic pleomorphism, hyperchromasia, necrosis, mitotic figures, or other features of malignancy are characteristically absent [
The various mucocutaneous non-LCH histiocytoses share some light microscopic features [
Elevated serum/plasma lipid levels help to differentiate PNH from eruptive histiocytoses that sometimes occur in association with hyperlipidemia [
Ever so often, the clinicopathologic features of histiocytoses manifest “shades of gray” rather than clear-cut clarity. Lesions with overlapping features have been described. Entities with JXG and PNH overlap are on record [
Comparison of clinicopathologic features of the different entities in the differential diagnosis of progressive nodular histiocytosis.
Clinicopathologic feature | PNH | BCH [ | JXG [ | AXG [ | GEH [ | XD [ | SRH/MRH [ | Dermatofibroma [ |
---|---|---|---|---|---|---|---|---|
Age at onset | Middle-aged to older adults | Typically in the first year of life | Childhood | Adulthood | Adults and children can be affected | Most before 25 years of age | Median age 35 years | Most common in the 20s to 40s |
Pattern of cutaneous manifestation | Multiple, widespread cutaneous papules and nodules | Multiple papules most commonly on the head and neck | Solitary cutaneous or subcutaneous nodules in up to 83% of cases | Solitary nodule in up two-thirds of cases | Dozens to hundreds of papules over the trunk and extremities | Multiple and widespread papules | Cutaneous papule(s) or nodule(s) | Usually solitary with predilection for the extremities |
Mucous membrane involvement | Yes | Rare | Yes | No | Rare | Yes | No (SRH); yes (MRH) | Yes (benign fibrous histiocytoma) [ |
Visceral involvement | Not usual | No | Yes, in up to 10% of cases | Not usual | Not usual | Yes | No (SRH); yes (MRH) | No |
Association with systemic disease | No | Not usual [ | Can occur | No | Not usual | Yes, 50% of cases associated with diabetes insipidus | MRH may be associated with systemic vasculitis [ | No |
Histology | Spindled lesional cells in the dermis | Demarcated infiltrates of tissue macrophages in the reticular dermis | Foamy and spindled mononuclear cells, Touton giant cells | Foamy and spindled mononuclear cells, Touton giant cells | Dermal collection of spindled cells and scattered Langhans giant cells | Macrophages with scalloped nuclei and foamy cytoplasm, as well as Touton and foreign body-type giant cells | Circumscribed aggregate(s) of oncocytic epithelioid cells in the upper and middermis | Poorly circumscribed dermal proliferation of spindled and epithelioid cells |
Clinical course | Usually progressive and unremitting | Frequently undergoes spontaneous regression | Spontaneous regression is common in children but less so in adults [ | Spontaneous regression is uncommon | Frequently undergoes spontaneous regression | Most frequently persistent; spontaneous regression is rare | Does not undergo spontaneous regression | Spontaneous regression is uncommon |
Recurrence | Yes | No | No | No | No | No | No | No |
PNH: progressive nodular histiocytosis; BCH: benign cephalic histiocytosis; JXG: juvenile xanthogranuloma; AXG: adult xanthogranuloma; GEH: generalized eruptive histiocytosis; XD: xanthoma disseminatum; SRH: solitary reticulohistiocytosis; MRH: multicentric reticulohistiocytosis.
Surgical excision remains the mainstay of treatment of PNH [
In summary, we present the case of a 37-year-old man with sudden onset of multiple cutaneous papules and nodules of PNH. The diagnosis of PNH is greatly dependent on clinicopathologic correlation. The unrelenting nature of the disease and its resistance to therapy makes it critical to distinguish PNH from several close mimics that, in many cases, follow a less relentless clinical course.
The authors declare no conflict of interest.
All authors have read and agreed to the published version of the manuscript.