UNASSIGNED: Secondary syphilis is well-known for its protean cutaneous manifestations and therefore very easy to be misdiagnosed.
UNASSIGNED: The current study was to observe the frequency of histopathological features characterizing secondary syphilis, and summarize the diseases most likely to be misdiagnosed.
UNASSIGNED: In this study a total of 129 pathological specimens from 114 patients with biopsy-proven secondary syphilis were retrospectively analysed and categorized according to clinicopathologic characteristics. The frequency of histopathological features characterizing secondary syphilis were analysed by comparison with clinical features.
UNASSIGNED: We found that in a single sample there is at least one feature or at most 13 features exist concurrently, and most demonstrated between 5 and 9 diagnostic features. Plasma cells (97.6% overall vs. 94.0% ≤ 6 features), endothelial swelling (86.8% vs. 74.0%), epidermis hyperplasia (73.6% vs. 62.0%) especially irregular acanthosis, lymphocytes infiltration (71.3% vs. 52.0%) and interstitial patterns (69% vs. 72.0%) were the most common findings in all cases as well as in cases with ≤ 6 features. Granulomatous inflammation is an uncommon histopathologic pattern in secondary syphilis (12.4%). The rash morphologies of our biopsies mainly manifesting as macules and maculopapules were more likely to have 6 or fewer features, which were not only easily misdiagnosed for pityriasis rosea, tinea and erythema multiforme, but also mostly taken from the trunk and genitalia. Atypical morphologies can be combined with plasma cell infiltration and T. pallidum immunohistochemical stain to confirm the diagnosis.
UNASSIGNED: In this study plasma cells from superficial and deep perivascular distribution to nodular infiltration were a crucial clue for diagnosis of secondary syphilis.

Glomerular endotheliosis is the pathognomonic glomerular lesion in pre-eclampsia that has also been described in those taking tyrosine kinase inhibitors for cancer treatment. Ibrutinib is a Bruton\'s tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia (CLL). We report the first known case of glomerular endotheliosis on kidney biopsy in a patient on ibrutinib monotherapy.
The patient presented with acute on chronic kidney disease, proteinuria, low C3 and C4 and a high rheumatoid factor titer. A kidney biopsy was performed to confirm a preliminary diagnosis of membranoproliferative glomerulonephritis (MPGN), the most common glomerular disease in patients with CLL. Unexpectedly, the kidney biopsy showed pre-eclampsia-like lesions on light and electron microscopy: occlusion of glomerular peripheral capillary lumens by swollen reactive endothelial cells. Findings of glomerulonephritis were not seen, and there were no specific glomerular immune deposits by immunofluorescence or electron microscopy.
CLL is known to cause glomerular lesions, mainly MPGN. There is increasing evidence that ibrutinib, a major treatment for CLL, can cause kidney disease, but the precise pathology is not characterized. We present a patient with CLL on ibrutinib with signs of glomerular endotheliosis. Based on the absence of CLL-induced kidney pathologies typically seen on the kidney biopsy and the non-selectivity of ibrutinib, we attributed the glomerular endotheliosis to ibrutinib. In pre-eclampsia, increased soluble fms-like tyrosine kinase 1 (sFlt1) levels induce endothelial dysfunction by decreasing vascular endothelial growth factor (VEGF). Ibrutinib has been demonstrated to have non-selective tyrosine kinase inhibition, including inhibition of VEGF receptor (VEGFR) and epidermal growth factor receptor (EGFR). VEGFR and EGFR inhibitors have recently been described in the literature to cause hypertension, proteinuria, and glomerular endotheliosis. Kidney biopsy should be performed in CLL patients on ibrutinib that present with acute kidney injury (AKI) or proteinuria to determine whether the clinical picture is attributable to the disease itself or a complication of the therapy.

BACKGROUND: To date, very few studies on clinical-histopathological correlations of cutaneous disorders associated with COVID-19 have been conducted.
METHODS: The Case 1 was a 90-year-old man, who tested positive for SARS-CoV-2 from a nasopharyngeal swab. Two days later, he was hospitalized and after eleven days transferred to Intensive Care Unit. A chest CT showed bilateral ground-glass opacities. Just that day, an erythematous maculo-papular rash appeared on trunk, shoulders and neck, becoming purpuric after few days. Histological evaluations revealed a chronic superficial dermatitis with purpuric aspects. The superficial and papillary dermis appeared edematous, with a perivascular lympho-granulocytic infiltrate and erythrocytic extravasation. At intraepithelial level, spongiosis and a granulocyte infiltrate were detected. Arterioles, capillaries and post-capillary venules showed endothelial swelling and appeared ectatic. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Regrettably, due to severe lung impairment, he died. The Case 2 was a 85-year-old man, admitted to Intensive Care Unit, where he was intubated. He had tested positive for SARS-CoV-2 from a nasopharyngeal swab two days before. A chest RX showed bilateral atypical pneumonia. After seven days, a cutaneous reddening involving trunk, upper limbs, neck and face developed, configuring a sub-erythroderma. Histological evaluations displayed edema in the papillary and superficial reticular dermis, and a perivascular lymphocytic infiltrate in the superficial dermis. The patient was treated with hydroxychloroquine, azithromycin, lopinavir-ritonavir and tocilizumab. Sub-erythroderma as well as respiratory symptoms gradually improved until healing.
CONCLUSIONS: The endothelial swelling detected in the Case 1 could be a morphological expression of SARS-CoV-2-induced endothelial dysfunction. We hypothesize that cutaneous damage could be initiated by endothelial dysfunction, caused by SARS-CoV-2 infection of endothelial cells or induced by immune system activation. The disruption of endothelial integrity could enhance microvascular permeability, extravasation of inflammatory cells and cytokines, with cutaneous injury. The Case 2 developed a sub-erythroderma associated with COVID-19, and a non-specific chronic dermatitis was detected at histological level. We speculate that a purpuric rash could represent the cutaneous sign of a more severe coagulopathy, as highlighted histologically by vascular abnormalities, while a sub-erythroderma could be expression of viral hematogenous spreading, inducing a non-specific chronic dermatitis.

BACKGROUND: Secondary syphilis is a sexually transmitted infection, which is referred to as \"the great imitator\" and has a wide spectrum of clinical manifestations. As a result, it is essential to identify potential secondary syphilis patients with ambiguous clinical manifestation through pathology.
OBJECTIVE: We sought to analyze the pathological features of secondary syphilis.
METHODS: We analyzed 59 biopsy specimens from 56 patients with secondary syphilis. Cases were classified according to the histological characteristics and clinical features.
RESULTS: Necrotic keratinocytes could be observed in 39 of 59 (66.1%) secondary specimens. Plasma cells (86.4%) were the most common finding overall. The presence of Treponema pallidum was detected mostly at the dermal-epidermal junction. There was no statistical significance between pathological features and age, HIV status, or RPR titer.
CONCLUSIONS: Necrotic keratinocytes are one of the characteristics of secondary syphilis. The combination of plasma cells, irregular acanthosis, elongated rete ridges, and endothelial swelling should increase the likelihood of syphilis.

BACKGROUND: Secondary syphilis has a wide spectrum of clinical and histologic manifestations.
OBJECTIVE: We sought to determine the frequency of histopathological features characterizing secondary syphilis, and which are most common in specimens displaying few diagnostic findings.
METHODS: In a multicenter, retrospective analysis of biopsy-proven secondary syphilis, cases were subcategorized by the number of histologic characteristics present.
RESULTS: The 106 cases mostly had 5 to 7 of the features studied. Many features were scarcer in cases with 5 or fewer features, including endothelial swelling (87.7% overall vs 72.4% ≤5 features), plasma cells (69.8% vs 48.3%), and elongated rete ridges (75.5% vs 27.6%). Specimens with 5 or fewer features were more likely to be truncal (61.1% vs 34.4% overall), demonstrate rete ridge effacement (44.8% vs 19.8%), and have pityriasis rosea (33.3% vs 17.2%) or drug eruption (33.3% vs 10.9%) in the clinical differential. An interstitial inflammatory pattern was the most common characteristic of specimens with 5 or fewer features (75.9%).
CONCLUSIONS: This was a retrospective review.
CONCLUSIONS: The independent value of many histologic features of syphilis may be overestimated. Combinations of endothelial swelling, interstitial inflammation, irregular acanthosis, and elongated rete ridges should raise the possibility of syphilis, along with the presence of vacuolar interface dermatitis with a lymphocyte in nearly every vacuole and lymphocytes with visible cytoplasm.