Kaposiform Hemangioendothelioma: clinicopathological characteristics of 8 cases of a rare vascular tumor and review of literature.

BACKGROUND: Kaposiform Hemangioendothelioma (KHE) is a rare vascular tumor of intermediate malignant potential which shows locally aggressive growth but only rarely metastasizes. It is mostly considered to be a tumor of pediatric population but its occurrence in the adults is not uncommon as once considered. Histologically, KHE can mimic other soft tissue neoplasms of different behaviors (e.g. Kaposi Sarcoma, hemangioma) and establishing the correct diagnosis is important for appropriate treatment. Herein, we describe the clinicopathological features of 8 cases of KHE which will be helpful in making their diagnosis. METHODS: We reviewed pathology reports, microscopy glass slides and obtained follow up information about 8 cases of KHE which were diagnosed at our institution from January 2008 till June 2020. Immunohistochemical stain for HHV8 was also performed. RESULTS: Age ranged from 7 months to 25 years. Seven patients were less than 20 years of age and one patient was 25 years old. Equal gender distribution was observed. Extremities were the most common sites of involvement, followed by head and neck, pancreas and ischiorectal region. 2 cases were resection specimen and all others were incisional biopsies. The largest tumor size was 5.5 cm in one of the resections. The incisional/fragmented tissues were all less than 5 cm in aggregate. Most cases showed predominance of nodular growth and a minor component of spindle cell population along with lymphangiomatosis like vascular channels, with evidence of microthrombi in 2 cases. Few multinucleated giant cells were observed in 2 cases. None of the cases exhibited significant nuclear atypia or mitotic activity. One of the cases arising in dermis showed underlying bone involvement. HHV8 was negative in 7/7 cases. CONCLUSIONS: KHE can also involve adult population and it should always be considered in the differential diagnoses of a vascular lesion. Presence of multinucleated giant cells is a rare finding. Knowledge about histological features and potential mimics is helpful in avoiding misdiagnosis.

Intravascular Colonization of Kaposi Sarcoma: Expanding the Spectrum of Specific Infiltrates of B-Cell Chronic Lymphocytic Leukemia.

B-cell chronic lymphocytic leukemia (CLL), a low-grade malignancy consisting of CD5(+), CD23(+), and CD43(+) small B lymphocytes, is the most frequent leukemia in the western world. Patients with CLL may exhibit skin changes characterized by histopathologic evidence of infiltration by atypical B lymphocytes, also known as "specific cutaneous infiltrates of CLL"; in addition, CLL is known to be associated with an increased risk of second cancers, including Kaposi sarcoma (KS). The combination of KS and CLL within the same cutaneous biopsy specimen has only rarely been described. We report a peculiar case of KS occurring in a patient with CLL, in which histopathological evaluation of KS lesions revealed prominent accumulation of CLL lymphocytes within neoplastic vascular spaces. We believe that our findings represent a novel example of intravascular colonization of vascular neoplasms by neoplastic lymphoid cells, further expanding the evergrowing spectrum of specific cutaneous infiltrates of CLL.

Anaplastic Kaposi's Sarcoma of the Adrenal in an HIV-negative Patient With Literature Review.

Kaposi's sarcoma (KS) is a peculiar tumor of viral etiology, with the HHV8 rhadinovirus playing a fundamental role in its development. Several epidemiological categories of KS have been identified, of which the sporadic, endemic, iatrogenic, and the epidemic are the main ones. Several histologic disease morphologies have been described, such as inflammatory, angiomatous, spindle cell, mixed, and the anaplastic (sarcomatous) subtypes. The skin of the limbs is most commonly affected, but any other organ or site may be involved. Microscopically KS may enter the differential diagnosis with several different entities, and for this purpose the immunohistochemical detection of the viral latent nuclear antigen-1 (LNA-1) may be crucial. Sporadic KS is usually benign, but rarely it may be aggressive. Anaplastic histology heralds an ominous course in any clinical context. We report a case of anaplastic retroperitoneal KS, occurring in an HIV-negative adult man. This patient presented with a huge left suprarenal mass, which was totally resected, and initially diagnosed as inflammatory leiomyosarcoma, because of the monomorphic spindle cell tumor morphology. After 12 years the tumor recurred locally as an unresectable mass, which was biopsied and examined. At the time of recurrence, the histologic slides of the primary tumor were reviewed, and the previous diagnosis was changed to that of atypical KS. Histologically the recurrent tumor showed both spindle cell and epithelioid appearances. Strongly diffuse HHV8/LAN-1 immunopositivity was documented in both tumors. The final diagnosis for the entire case was anaplastic KS. Then, the patient died in a few months.

mTOR, VEGF, PDGFR, and c-kit signaling pathway activation in Kaposi sarcoma.

Kaposi sarcoma (KS) is a locally progressive, intermediate-grade vascular neoplasm with no known cure, high recurrence rates, and potential for wide dissemination. Low efficacy and high toxicity limit current therapeutic options for advanced disease. Activation of mammalian target of rapamycin (mTOR), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and c-kit signaling pathways has been implicated in KS pathogenesis and may suggest a role for targeted inhibitors. KS cases were retrospectively retrieved (N=274), most (90%) associated with human immunodeficiency virus. Tissue microarray slides were stained with human herpes virus-8, Friend leukemia integration 1 transcription factor, CD117 (c-kit), phospho-S6 (pS6), PDGF receptor-ß, VEGF, and phospho-mTOR. Both intensity and extent of staining were scored. Multiplying these scores for each core yielded total staining H-scores. Human herpes virus-8 was positive in 87% and Friend leukemia integration 1 transcription factor in 95.7% of cases. Most were also VEGF+ (97.6%), pS6+ (95.7%), CD117+ (92.5%), and PDGFRB+ (87.4%). Approximately half (55.6%) were phospho-mTOR+. There was no significant difference in staining among patients with low (<500 cells/mm3) or preserved CD4 T-cell counts. Immunohistochemistry confirms upregulation of the mTOR, PDGF, VEGF, and c-kit pathways in a large cohort of KS samples. Of proteins tested, pS6, downstream of mTOR, demonstrated the highest proportion of strong positivity (67.1%). These results support the possibility of using targeted inhibitors in KS. Overexpression was independent of CD4 count, suggesting that even patients with low counts may be targeted therapy candidates.

Successful Everolimus Treatment of Kaposiform Hemangioendothelioma With Kasabach-Merritt Phenomenon: Clinical Efficacy and Adverse Effects of mTOR Inhibitor Therapy.

Kasabach-Merritt phenomenon (KMP) is a life-threatening consumptive coagulopathy associated with underlying kaposiform hemangioendothelioma (KHE) in infancy. We describe the case of a 3-month-old girl with KHE complicated by KMP who responded dramatically to treatment with everolimus, a mechanistic target of rapamycin (mTOR) inhibitor. Immunohistochemical expression of mTOR was found in the KHE biopsy specimens, which may explain the improvement of KMP and reduction in KHE tumor size with mTOR inhibitor treatment. This effective use of everolimus may shed light on the emerging role of mTOR signaling in the development and pathogenesis of KHE and KMP.

Variability of HHV8 LNA-1 Immunohistochemical Staining Across the 3 Histologic Stages of HIV-Associated Mucocutaneous Kaposi Sarcoma: Is There a Relationship to Patients' CD4 Counts?

The histologic diagnosis of Kaposi sarcoma (KS) can be confirmed with human herpes virus 8 (HHV8) latency-associated nuclear antigen (LNA)-1 immunohistochemistry, which may show variability in distribution and intensity. This retrospective study was aimed at addressing the factors that may contribute to this variability. All cases of mucocutaneous KS diagnosed in a 5-year period at the histopathology department at a tertiary hospital in South Africa with available patients' CD4 counts and HHV8 LNA-1 immunohistochemically stained slides were reviewed, and the biopsy stages of KS (patch/plaque/nodular), CD4 counts, immunohistochemistry staining method (manual vs. automated), and distribution (diffuse/focal) and intensity (strong/weak) of HHV8 LNA-1 staining were recorded. A total of 127 cases were reviewed. No relationship was demonstrated between the median CD4 count and the histologic stages of KS (P = 0.701) or the intensity and distribution of HHV8 immunohistochemical staining using either staining method. Multivariate analysis showed that method of immunohistochemical staining was a significant predictor of distribution (P = 0.006) and intensity (P = 0.044) of staining, and that stage was a significant predictor of distribution of staining (P = 0.033).

Disseminated Kaposi sarcoma in a HIV negative patient.

Kaposi sarcoma (KS) is a neoplasm of the endothelial cells. It often manifests with multiple vascular nodules on the skin and other organs. It is a systemic, malignant and multifactor disease and has a variable course. We describe an elderly Chinese man who had a rapidly growing maroon nodule on his right foot, both arms and cheekbones. KS in HIV-negative patients has only been reported sporadically.

Acute upper gastrointestinal bleeding secondary to Kaposi sarcoma as initial presentation of HIV infection.

Despite our decades of experience with Kaposi Sarcoma its true nature remains elusive. This angioproliferative disease of the vascular endothelium has a propensity to involve visceral organs in the immunocompromised population. There are four variants of the disease and each has its own pathogenesis and evolution. While the common sources of upper gastrointestinal bleeding are familiar to surgeons and critical care physicians, here we present the exceedingly rare report of upper gastrointestinal bleeding attributable to this malady, explore its successful management, and review the various forms of Kaposi Sarcoma including the strategies in regard to their management.

Kaposiform hemangioendothelioma complicated by Kasabach-Merritt phenomenon: ultrastructural observation and immunohistochemistry staining reveal the trapping of blood components.

Kaposiform hemangioendothelioma (KHE), a borderline tumor of endothelial origin, is associated with Kasabach-Merritt phenomenon, characterized by profound thrombocytopenia and consumptive coagulopathy resulting from the localized intravascular coagulation (LIC) in the tumor. Previous studies have suggested that the trapping of blood components, including platelets, may underlie the LIC in KHE. However, more evidence is needed to support this hypothesis. In this study, one case of a Chinese infant with a KHE in the left arm was complicated by Kasabach-Merritt phenomenon. The tumor was partially resected and the sample was used for ultrastructural observation and immunohistochemistry staining of Glut-1. Ultrastructural observation found the trapping of erythrocytes, platelets, macrophages, and lymphocytes in the slit-like channels of the tumor nodules, and phagocytic vesicles in the cytoplasm of neoplastic cells. Immunohistochemistry staining further showed numerous Glut-1(+) erythrocytes in the channels. In conclusion, our results provided compelling morphological evidence of the trapping of blood components in KHE, which may interpret the LIC in the tumor and subsequent consumptive coagulopathy.

Diagnostic value of endothelial markers and HHV-8 staining in gastrointestinal Kaposi sarcoma and its difference in endoscopic tumor staging.

AIM: To clarify the diagnostic values of hematoxylin and eosin (HE), D2-40, CD31, CD34, and HHV-8 immunohistochemical (IHC) staining in gastrointestinal Kaposi's sarcoma (GI-KS) in relation to endoscopic tumor staging. METHODS: Biopsy samples (n = 133) from 41 human immunodeficiency virus-infected patients were reviewed. GI-KS was defined as histologically negative for other GI diseases and as a positive clinical response to KS therapy. The receiver operating characteristic area under the curve (ROC-AUC) was compared in relation to lesion size, GI location, and macroscopic appearances on endoscopy. RESULTS: GI-KS was confirmed in 84 lesions (81.6%). Other endoscopic findings were polyps (n = 9), inflammation (n = 4), malignant lymphoma (n = 4), and condyloma (n = 2), which mimicked GI-KS on endoscopy. ROC-AUC of HE, D2-40, blood vessel markers, and HHV-8 showed results of 0.83, 0.89, 0.80, and 0.82, respectively. For IHC staining, the ROC-AUC of D2-40 was significantly higher (P < 0.05) than that of HE staining only. In the analysis of endoscopic appearance, the ROC-AUC of HE and IHC showed a tendency toward an increase in tumor staging (e.g., small to large, patches, and polypoid to SMT appearance). D2-40 was significantly (P < 0.05) advantageous in the upper GI tract and for polypoid appearance compared with HE staining. CONCLUSION: The diagnostic value of endothelial markers and HHV-8 staining was found to be high, and its accuracy tended to increase with endoscopic tumor staging. D2-40 will be useful for complementing HE staining in the diagnosis of GI-KS, especially in the upper GI tract and for polypoid appearance.

Histopathological analysis of vesicular and bullous lesions in Kaposi sarcoma.

BACKGROUND: In this study, the clinical and morphological features of vesiculobullous lesions observed in Kaposi sarcoma are analyzed, and the features of bullous Kaposi sarcoma cases are emphasized. METHODS: A total of 178 biopsy materials of 75 cases diagnosed as classic-type cutaneous Kaposi sarcoma were reviewed. Twenty-five cases showing vesiculobullous features were included in the study. Tumor, epidermis, dermis, and clinical data regarding these cases was evaluated. RESULTS: Vesicular changes were observed in 21 (12%) out of 178 lesions of the 75 cases, while bullous changes were present in only 4 (2%). In all cases where vesicular and bullous changes were detected, tumor, epidermis, and dermis changes were similar. All cases were nodular stage KS lesions, whereas hyperkeratosis and serum exudation in the epidermis, marked edema in the dermis, and enlarged lymphatic vessels and chronic inflammatory response were observed. CONCLUSIONS: Our findings suggest that changes in vascular resistance occurring during tumor progression are the most important factors comprising vesiculobullous morphology. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1646397188748474.

Computational analysis predicts the Kaposi's sarcoma-associated herpesvirus tegument protein ORF63 to be alpha helical.

The innate immune response provides our first line of defence against infection. Over the course of evolution, pathogens have evolved numerous strategies to either avoid activating or to limit the effectiveness of the innate immune system. The Kaposi's sarcoma-associated herpesvirus (KSHV) contains tegument proteins in the virion that contribute to immune evasion and aid the establishment of viral infection. For example, the KSHV tegument protein ORF63 modulates inflammasome activation to inhibit the innate immune response against the virus. Understanding the likely structure of proteins involved in immune evasion enables potential mechanisms of action to be proposed. To understand more fully how ORF63 modulates the innate immune system we have utilized widely available bioinformatics tools to analyze the primary protein sequence of ORF63 and to predict its secondary and tertiary structure. We found that ORF63 is predicted to be almost entirely alpha-helical and may possess similarity to HEAT repeat containing proteins. Consequently, ORF63 is unlikely to be a viral homolog of the NLR protein family. ORF63 may inhibit the innate immune response by flexibly interacting with its target protein and inhibiting the recruitment of protein co-factors and/or conformational changes required for immune signaling.

Clinical, histological and immunohistochemical findings in oral Kaposi's sarcoma in a series of Mexican AIDS patients. Comparative study.

BACKGROUND: The origin of spindle cells (SC) in oral Kaposi's sarcoma (OKS) is still an intriguing aspect. Thus the aim of the present study was to compare the clinical, histological and immunohistochemical characteristics of OKS and oral pyogenic granuloma (OPG), in order to contribute to the knowledge of the cells involved in Kaposi's sarcoma pathogenesis. METHODS: In this retrospective, observational and comparative study, 39 OKS and 30 OPG cases were included. Immunohistochemical studies were performed for vimentin, alpha SMA, desmin, C-kit, CD34, D2-40 and LANA-1 [human herpesvirus-8(HHV-8)]. Statistical comparisons were done using the chi-square and Wilcoxon-Mann-Whitney rank sum tests. RESULTS: Fourteen (35.9%) OKS cases also affected the skin, and 83.8% involved the palate. All OKS and OPG were positive for vimentin and CD34. OKS samples were positive for alpha SMA, and 25.6% expressed C-kit. All OKS cases were positive for HHV-8, and the number of positive cells increased significantly from early / intermediate to late histological stage. D2-40 was expressed in the cellular component and vascular walls of all OKS cases, but it was negative in OPG. HHV-8 expression was increased in late histological stages of OKS lesions. CONCLUSIONS: The expression of D2-40 marker in the vascular walls and SC supports the view of a lymphatic differentiation in neoplastic cells of OKS. Desmin, alpha SMA, D2-40, C-kit and HHV-8 were the main markers differently expressed in OKS and OPG.

An "anaplastic" Kaposi's sarcoma mimicking a Stewart-Treves syndrome. A case report and a review of literature.

Cutaneous angiosarcoma (AGS) developing in a lymphedematous arm, after lymphadenectomy in the context of breast cancer, is the definition of the classical Stewart-Treves syndrome. Like AGS, many tumors such as Kaposi's sarcoma (KS) could develop in chronic lymphedema. We describe the case of a 50-year-old woman who presented with several nodules on the left lymphedematous arm evocative of a Stewart-Treves syndrome, 2 years after a left mastectomy and a homolateral lymphadenectomy. The histological examination revealed an atypical vascular proliferation suggesting AGS, but endothelial atypical cells nuclei were strongly stained by herpes human virus 8 antibody. The final diagnosis was an "anaplastic" KS mimicking a Stewart-Treves syndrome. The total regression of the lesion was obtained by elastic contention and intradermic liposomal doxorubicin. "Anaplastic" KS is a rare histological form of nodular KS, which mimics a cutaneous AGS but classically expresses herpes human virus 8. It is essential to know about this entity, particularly in a lymphedematous arm, to avoid aggressive treatment such as amputation.

Intestinal Kaposi's sarcoma may mimic gastrointestinal stromal tumor in HIV infection.

Diffuse intestinal Kaposi's sarcoma shares macroscopic and histopathologic features with gastrointestinal stromal tumors. Correct diagnosis may pose a clinical challenge. We describe the case of a young HIV-1-infected African lady without advanced immunodeficiency, who presented with a diffuse spindle cell tumor of the gut. Initial diagnosis was of a gastrointestinal stromal tumor, based on endoscopy and histopathology. Further evaluation revealed evidence for human herpesvirus 8 (HHV8) and the diagnosis had to be changed to diffuse intestinal Kaposi's sarcoma. Antiretroviral triple therapy together with chemotherapy was commenced, and has led to the rapid remission of intestinal lesions. With a background of HIV infection, the presence of HHV8 as the causative agent of Kaposi's sarcoma should be determined, as distinct treatment is indicated.

Conjunctival Kaposi's sarcoma in a nonimmunocompromised patient.

CASE REPORT: We report a case of conjunctival Kaposi's sarcoma (KS) in a nonimmunocompromised patient. The resected tumour recurred locally. No additional lesion was seen 20 months after the second surgery. COMMENTS: Before onset of AIDS, few reports described primary conjunctival KS, although it has been described in other immunocompromised disease stages, i.e. systemic KS.

Classic Kaposi's sarcoma presenting first with gastrointestinal tract involvement in a HIV-negative Inuit male--a case report and review of the literature.

Kaposi's sarcoma (KS) is a multicentric low-grade vascular malignancy. In North America, it is usually seen in AIDS and solid organ transplant populations. Classic KS is a subtype that traditionally occurs in elderly HIV-negative males of Mediterranean, Eastern European, and Jewish descent. Patients with classic KS characteristically present with skin lesions in the distal extremities. Involvement of the viscera is uncommon in classic KS, but may occur in the late stages of the disease. We report the first case of classic KS presenting in the gastrointestinal tract of an elderly HIV-negative Inuit male from Northern Quebec, Canada.