Abstract
A 60-year-old man presented with persistent dysphagia and weight loss of 2-months duration. An upper GI endoscopy revealed mycotic oesophagitis and chronic gastritis with two ulcers of the gastric body and antrum. Repeat endoscopy was performed after medical treatment failed, and histological examination on new biopsy samples led to a diagnosis of Kaposi sarcoma of the stomach. HIV infection was not known at this time; however, the patient was tested after the diagnosis of Kaposi sarcoma was made and found to be HIV positive. An adequate biopsy sampling was required for histological diagnosis and the use of immunohistochemical markers, especially human herpesvirus 8 (HHV8) antibodies, supplied valid diagnostic support. This case underlines the importance of an accurate evaluation of vascular proliferation in gastrointestinal biopsies even in patients without clinical evidence of HIV-related pathology.
BACKGROUND
Kaposi sarcoma (KS) of the gastrointestinal (GI) tract was very rare before the AIDS epidemic. GI involvement can precede, be synchronous, or develop without the appearance of the skin lesions. Typically, GI KS is asymptomatic, but may present with gastric outlet obstruction, intussusceptions or bleeding.1,2 However, dysphagia caused by gastric KS as the presenting symptom of AIDS is exceptional.
CASE PRESENTATION
A 60-year-old man was admitted to the Gastroenterology unit of our hospital with a 2-month history of persistent dysphagia for liquid and solid foods. The patient smoked 10 cigarettes a day, drank moderate quantities of alcohol and his medical history was unremarkable. Oesophagogastroduodenoscopy revealed pseudomembranes throughout the length of the oesophagus and two ulcerative lesions with thickened borders in the gastric body and antrum (fig 1). Multiple biopsy samples were taken on the distal oesophagus and on the borders of the gastric ulcers. Histological analysis at that time revealed mycotic oesophagitis and acute gastritis with ulceration. After medical therapy with a proton pump inhibitor and itraconazole, the patient showed improvement but no disappearance of the symptoms. Clinical evaluation ruled out diabetes mellitus and the use of immunosuppressive drugs. A repeat endoscopy showed no macroscopic changes of the gastric ulcers, and further biopsy samples were obtained from the base and ulcer margins. Histopathologically, the lesions consisted of spindle cell and capillary sized vascular proliferation (fig 2). These findings were consistent with KS of the stomach.
Figure 1.
Endoscopic image of ulcerative lesion in the gastric antrum. The gross appearance shows the haemorrhagic central area surrounded by thickened mucosal borders.
Figure 2.
Kaposi sarcoma of the stomach. The tumour is composed of spindle-shaped cells, forming slit-like spaces with infiltration between glands accompanied by a variably mixed mononuclear inflammatory cell infiltrate. EE, extravasated erythrocytes.
The patient was subsequently tested for HIV infection and found to be positive.
INVESTIGATIONS
Sections (3 μm) from buffered, formalin fixed, paraffin embedded tissues were created and stained with H&E. Perls and periodic acid–Schiff (PAS) stainings were also performed. Immunohistochemical studies were performed using the avidin-biotin-peroxidase system (ABComplex, Dako, Glostrup, Denmark). The reagents are listed in table 1.
Table 1.
Antibodies for immunohistochemical study
| Antibodies | Clone | Supplier | Dilution |
| CD34 | QBEnd/10 | Lab Vision Corporation | Ready to use |
| Actin smooth muscle | 1A4 | Lab Vision Corporation | 1:100 |
| S100 | Polyclonal | Dako | Ready to use |
| CD117 | Polyclonal | Dako | 1:40 |
| HHV8-LNA1 | 13B10 | Novo Castra | 1:25 |
| Fli-1 | Polyclonal | Lab Vision Corporation | 1/20 |
| D2-40 | D2-40 | Signet | 1:40 |
Fli-1, Friend leukaemia virus integration 1; HHV8, human herpesvirus 8; LNA1, latent nuclear antigen 1.
The histological picture of the oesophageal mucosa showed a severe oesophagitis with numerous yeast and pseudohyphal fungal forms that were positive on PAS staining. The gastric lesions of the first sample showed chronic gastritis with an exudative component. In the gastric specimens of repeat endoscopy both ulcerative lesions consisted of spindle cell proliferation (fig 2) with slit formation and markedly dilated capillary proliferation accompanied by extensive red blood cell extravasation and moderate lymphocytic and plasma cell infiltrate with deposition of brown haemosiderin-like pigment (fig 3). Infiltration of the gastric glands by spindle cells was observed. Some tumour cells presented PAS-positive (fig 4) hyaline globules. On immunohistochemistry, the tumour tested positive for CD34 (fig 5), factor VIII, D2-40, Friend leukaemia virus integration 1 (Fli-1) and latent nuclear antigen 1 (LNA1) (fig 6), and negative for S100 and α smooth muscle actin.
Figure 3.
The spindle cells in some areas with the appeared of fibroblasts packed the lamina propria. The nuclei are elongated and plump. Note the extravasated erythrocytes (EE) within the neoplastic cells.
Figure 4.
Some neoplastic cells showed periodic acid–Schiff (PAS) positive hyaline globules intracytoplasmatically.
Figure 5.
The lesional cells display immunoreactivity for the CD34. The glandular cells are negative (arrow) (DAB).
Figure 6.
Immunohistochemistry. All tumour cells display strong nuclear immunoreactivity for human herpesvirus 8 (HHV8)-latent nuclear antigen 1 (LNA1) antibody (DAB).
DIFFERENTIAL DIAGNOSIS
On clinical grounds KS of the stomach has to be differentiated from peptic ulcers and gastric cancer. Microscopically, KS can mimic benign lesions such as granulation tissue and bacillary angiomatosis, and malignant neoplasms such angiosarcoma, spindle cell melanoma and gastrointestinal stromal tumour (GIST).
DISCUSSION
GI involvement with KS is frequent in patients with advanced HIV disease.5–7 In our case the HIV infection was not known at the time of presentation and the patient’s GI symptoms were not associated with other symptoms that could lead to the suspicion of AIDS. In typical cases of gastric KS upper endoscopy reveals red–purple nodules,1 whose sampling does not need particular precautions.1,8 However, occasionally the endoscopic findings are more similar to common benign lesions, such as peptic ulcer.9 In cases like the one we have described, the adequacy of the sampling is critical to reach a diagnosis. Sampling limited to the borders of the ulcer, which is generally sufficient to differentiate peptic lesions from carcinoma, may fail in the diagnosis of stromal proliferation.10,11 Accurate evaluation of vascular proliferation is essential to differentiate reactive vascular hyperplasia from KS. The key histological features are the presence of “slit-like” vascular spaces, atypical endothelial cells and extravasated red blood cells, which are normally absent in granulation tissue. Moreover, while both conditions are CD34 positive, the latter is human herpesvirus 8 (HHV8) negative on immunohistochemistry.9 Immunohistochemistry is also useful to differentiate KS from other stromal lesions that may mimic the clinical and morphological appearance of GI KS. These include spindle cells melanoma, inflammatory pseudotumours, leiomyosarcomas and GIST, which are all negative for endothelial cell markers.4,7,12
HHV8 is known to be a initiator and a promoter as well of all forms of KS.3,4 The nuclear positivity with the monoclonal antibody LNA1, which binds HHV8, is very sensitive and specific, and confirms the aetiological link between human HHV8 and KS.12–14 Antibodies to CD34 and HHV8 are the minimally-required immunohistochemical markers for KS diagnosis. Other supportive investigations have been used to better define the lesion.
Previous studies demonstrated KS of internal organ localisation, in absence of the cutaneous form, in 37% of patients who are HIV positive.10 Therefore, in the presence of gastric ulcers and clinical signs of immunodeficiency, a diagnosis of KS of the stomach should be considered in the differential diagnosis.7
In our case the diagnosis of primary gastric KS was the first sign of HIV infection.
LEARNING POINTS
Gastrointestinal Kaposi sarcoma (KS) may have been the source of a diagnostic mistake.
Adequate biopsy sampling and immunohistochemical positivity for CD34 and, in particular, for human herpesvirus 8 (HHV8) antibodies are the minimally-required investigation for the diagnosis.
This case underlines the importance of an accurate evaluation of vascular proliferation in gastrointestinal biopsies even in patients without clinical evidence of HIV-related pathology.
Footnotes
Competing interests: None.
Patient consent: Patient/guardian consent was obtained for publication.
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