Hamazaki‐Wesenberg bodies in two patients with no history of sarcoidosis

Patient A

A 76‐year‐old woman underwent a left nephrectomy for a retroperitoneal angiomyolipoma, which was contacting and displacing the spleen and left kidney. Intraoperative frozen sections of a periportal lymph node revealed brown pigment within the sinuses. Permanent sections of this specimen demonstrated a reactive lymph node with lipogranuloma formation, prominent histiocytes, and ovoid, dark‐brown to yellow structures located within the sinuses, associated with the prominent histiocytes. These structures ranged from 0.25–1.0 times the size of a lymphocyte nucleus and were primarily extracellular, with only occasional examples noted within histiocytes.

Patient B

A 55‐year‐old man underwent a right hemicolectomy for a tubulovillous adenoma of the ascending colon. Preoperative CT scan revealed mildly enlarged retroperitoneal lymphadenopathy, but no other evidence of metastasis. Eleven lymph nodes were located within the pericolic adipose tissue of the specimen, all negative for malignancy. Three of the eleven nodes demonstrated ovoid, dark‐brown structures within the subcapsular sinuses, as well as lipogranuloma formation in one node. As in case 1, these structures were 0.25–1.0 times the size of a lymphocyte nucleus and were primarily extracellular, associated with histiocytes within the subcapsular sinuses.

Discussion

Hamazaki‐Wesenberg bodies (alternatively termed yellow‐brown bodies, yellow bodies, Hamazaki corpuscles) are structures of unknown significance, which have been periodically documented in the sinuses of lymph nodes in numerous anatomic locations and myriad medical conditions, including appendicitis, cirrhosis, lymphoid tumours, colon carcinoma and numerous others, most famously sarcoidosis.¹,²,³,⁴,⁵,⁶ Initially described by Hamazaki in 1938 in mesenteric lymph nodes,⁶ and later noted by Menne in 1952 in 70% of mesenteric lymph nodes removed during appendectomies,¹ there was renewed interest in these formations in the 1960s when it was hypothesised that these bodies were specific for sarcoidosis.⁴,⁷

Subsequent research has demonstrated Hamazaki‐Wesenberg bodies to be no more prevalent in sarcoidosis than in other conditions; likewise, theories proposing a mycobacterial aetiology have been similarly discounted.³ Whereas the precise origins of these phenomena remain elusive, mistaking these structures for pigmented fungal organisms, particularly in cases where patients are immunocompromised and the threshold for infectious diagnoses is very low,² is a diagnostic pitfall with severe consequences. Recognising Hamazaki‐Wesenberg bodies can be complicated by the variable size and close proximity of such bodies to one another, which can mimic budding yeast,⁸ and positive staining with both Gomori methenamine silver (GMS) and predigested periodic acid‐Schiff (PASD), both of which are commonly used for fungi.²

Accurate diagnosis of Hamazaki‐Wesenberg bodies thus relies on the diagnosing pathologist meticulously examining the morphology of any potential fungal organisms located on H&E stained slides, and maintaining this diagnostic vigilance when examining any additional stains ordered. While these bodies typically show a yellow‐brown colouring on H&E, this can vary substantially; therefore, supplementary stains may be of assistance (fig 1). Since both Hamazaki‐Wesenberg bodies and numerous fungal organisms react with GMS and predigested PAS, stains such as the Fontana‐Masson silver or acid‐fast staining for ceroid may be helpful in differentiating a fungus from a viceroy.² The ceroid nature of Hamazaki‐Wesenberg bodies has been postulated by Sieracki and Fisher, and acid‐fast staining for ceroid (long Ziehl‐Neelson acid fast) has been shown to react with the bodies, whereas standard Ziehl‐Neelson acid‐fast technique may be weakly positive or negative.²,³,⁹ The Fontana‐Masson silver stain may be particularly useful in such diagnostic dilemmas given that, with the exception of Cryptococci, fungi are generally non‐reactive to this stain whereas Hamazaki‐Wesenberg bodies do react.²

Figure 1 (A) H&E stained section at 60× magnification demonstrating numerous, variably sized, yellow‐brown structures associated with histiocytes within the subcapsular sinus. Multiple bodies in close proximity can simulate budding yeast (arrow). (B) Fontana‐Masson silver (FMS) stain emphasises the Hamazaki Wesenberg bodies, colouring them black, though there can be artifact from debris associated with this stain. (C) Gomori methenamine Silver (GMS) likewise accents these bodies, darkly staining them against a green background. (D) Periodic acid‐Schiff with an amylase digest (PAS‐D) highlights the bodies, imparting on them a bright red colour.

Take‐home message

Hamazaki‐Wesenberg bodies can be found in lymph nodes in many diverse disease processes and supplementary stains can help differentiate them from fungi, sparing patients unnecessary exposure to antifungal medications.