The Great Mimicker Strikes Again

Hepatic Secondary Syphilis Can Cause a Variety of Histologic Patterns and May Be Negative for Treponeme Immunohistochemistry

“…15,16,24,25,28,30,37,43,45,[49][50][51]54,55,57 Erythrophagocytosis is rarely mentioned. 39 Central vein necroinflammatory activity, noted by Fehér et al 25 as "appear[ing] to be characteristic of syphilitic hepatitis," was only seen in 3 of our 14 cases. IHC for Treponema organisms could be considered a gold standard for diagnosing liver involvement by syphilis.…”

“…These nonspecific cases, as well as cases with a more defined pattern of injury, may include "supportive" findings seen in numerous cases in our study and others, which may help suggest the diagnosis of hepatic secondary syphilis but do not indicate a particular pattern of injury. These include prominent Kupffer cells (described in many studies in various patterns, 17,24,25,28,30,31,33,34,43,48,51,57 including 1 case with prominent sinusoidal histiocytes 39 ), poorly formed non-necrotizing granulomata 27,39,42,46,50,56,58 (which may rarely be the predominant finding 46 ), vessel wall inflammation, [25][26][27][28]39,51 sinusoidal inflammation, 9,28,29,39 and hepatic necrosis. 15,16,24,25,28,30,37,43,45,[49][50][51]54,55,57 Erythrophagocytosis is rarely mentioned.…”

“…Among the negative cases, 3 patients received treatment for syphilis shortly before biopsy, and the fourth was treatment-naive. Similarly, reported cases of hepatic syphilis in the literature include cases that were positive 9,17,[23][24][25][26][27][28][29]35,[39][40][41]45,46,50,59 and cases that were negative 9,15,16,18,20,25,28,30,31,33,34,38,[42][43][44][47][48][49]51,52,54,55,57 for spirochetes. Before the introduction of the IHC stain, the Warthin-Starry histochemical stain was used for this purpose, although this stain is notoriously difficult to interpret 61 and insensitive.…”

“…In 1984, Terry et al24 examined the liver of 22 patients with “early syphilis,” stating that 10 liver biopsies were normal, 9 showed mild/nonspecific changes (including Kupffer cell hyperplasia and necrosis), and 3 showed reactive hepatitis with portal inflammation and lobular necrosis. While these case series offered new data on hepatic secondary syphilis, a 1985 clinical review of liver involvement in early syphilis noted that “[t]he histologic appearances of the liver in reported cases had conflicting findings.”12 In the decades since, further histologic examination of secondary hepatic syphilis has been limited to case reports describing 1 to 3 cases, also with varied findings and no particular unifying themes,9,13–18,20,23,26,27,29–31,33–59 (see Table, Supplemental Digital Content 1, which summarizes histologic findings in these case reports and in the earlier case series, http://links.lww.com/PAS/B289). Some of these are included in a systematic review of clinical and pathologic findings in hepatic secondary syphilis by Huang et al,10 who noted that common findings included portal or lobular inflammation, necrosis, cholestasis, and granulomata; most cases included in that review did not undergo liver biopsy or describe histopathology.…”

“…These include prominent Kupffer cells (described in many studies in various patterns,17,24,25,28,30,31,33,34,43,48,51,57 including 1 case with prominent sinusoidal histiocytes39), poorly formed non-necrotizing granulomata27,39,42,46,50,56,58 (which may rarely be the predominant finding46), vessel wall inflammation,25–28,39,51 sinusoidal inflammation,9,28,29,39 and hepatic necrosis 15,16,24,25,28,30,37,43,45,49–51,54,55,57. Erythrophagocytosis is rarely mentioned 39. Central vein necroinflammatory activity, noted by Fehér et al25 as “appear[ing] to be characteristic of syphilitic hepatitis,” was only seen in 3 of our 14 cases.…”