Cutaneous mastocytosis with atypical mast cells and giant cytoplasmic granules.

A 12-year-old male presented with an 8-year history of five firm cream colored papules on the right vertex of the scalp. A biopsy showed a dense infiltrate of monomorphous mast cells involving the dermis and extending into the subcutis. A relatively well-circumscribed cluster of larger cells showed pleomorphic nuclei with bilobed and multilobed morphology. Both mast cell populations had an eosinophilic cytoplasm filled with granules ranging in size from small to giant forms. By immunohistochemistry, the cells expressed CD117, tryptase and CD68, and were negative for AE1/AE3, CD1a, CD2 and CD25. S-100 staining revealed only faint cytoplasmic positivity and myeloperoxidase had an inhomogeneous patchy pattern, with an overall staining of less than 5% of the cells. A diagnosis of cutaneous mastocytosis was made and after 6 months follow-up, no progression observed. Clinical correlation and awareness of these unusual morphologic features as being part of the spectrum of cutaneous mastocytosis are important to avoid an erroneous diagnosis of malignancy. Although pleomorphic, multilobed nuclear morphology and giant cytoplasmic granules have not been associated with an aggressive behavior or systemic mastocytosis, close clinical observation is warranted in this context.

CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer.

INTRODUCTION: Tumor infiltrating lymphocytes may indicate an immune response to cancer development, but their significance remains controversial in breast cancer. We conducted this study to assess CD8+ (cytotoxic T) lymphocyte infiltration in a large cohort of invasive early stage breast cancers, and to evaluate its prognostic effect in different breast cancer intrinsic subtypes. METHODS: Immunohistochemistry for CD8 staining was performed on tissue microarrays from 3992 breast cancer patients. CD8+ tumor infiltrating lymphocytes were counted as intratumoral when in direct contact with tumor cells, and as stromal in adjacent locations. Kaplan-Meier functions and Cox proportional hazards regression models were applied to examine the associations between tumor infiltrating lymphocytes and breast cancer specific survival. RESULTS: Among 3403 cases for which immunohistochemical results were obtained, CD8+ tumor infiltrating lymphocytes were identified in an intratumoral pattern in 32% and stromal pattern in 61% of the cases. In the whole cohort, the presence of intratumoral tumor-infiltrating lymphocytes was significantly correlated with young age, high grade, estrogen receptor negativity, human epidermal growth factor receptor-2 positivity and core basal intrinsic subtype, and was associated with superior breast cancer specific survival. Multivariate analysis indicated that the favorable prognostic effect of CD8+ tumor infiltrating lymphocytes was significant only in the core basal intrinsic subgroup (Hazard ratio, HR = 0.35, 95% CI = 0.23-0.54). No association with improved survival was present in those triple negative breast cancers that lack expression of basal markers (HR = 0.99, 95% CI = 0.48-2.04) nor in the other intrinsic subtypes. CONCLUSIONS: CD8+ tumor infiltrating lymphocytes are an independent prognostic factor associated with better patient survival in basal-like breast cancer, but not in non-basal triple negative breast cancers nor in other intrinsic molecular subtypes.

Prognostic significance of CD8+ T lymphocytes in breast cancer depends upon both oestrogen receptor status and histological grade.

AIMS: Results of previous studies on the influence of tumour infiltrating lymphocytes on prognosis of women with breast cancer have been mixed. This study re-evaluates the role of tumour-infiltrating lymphocytes as a prognostic marker in women with breast cancer. METHODS AND RESULTS: Immunochemistry staining of CD8(+) T cells was performed on a tissue microarray of 1953 breast carcinomas. When all tumours were considered, no association between the lymphocyte count and patient survival was found. In univariate analysis, there was a reduced disease-specific survival for women with oestrogen receptor (ER)-positive tumours with high intraepithelial lymphocyte count (P=0.004). In those with ER-negative tumours, the disease-specific survival was improved when the intraepithelial, stromal and total lymphocyte counts were high, the total lymphocyte count also being an independent prognostic marker on multivariate analysis (P=0.031). When stratified by histological grade, on univariate analysis, the previously observed inferior outcome in women with high lymphocyte count and ER-positive tumours remained significant only if tumours were also of low grade, and the superior outcome in those with ER-negative tumours remained significant if tumours were also of high grade. CONCLUSIONS: Our results raise the possibility of different immune-tumour interactions based on ER status and histological grade.

Testicular vasculitis: a series of 19 cases.

OBJECTIVES: Because of limited reported cases, it is unknown how often testicular vasculitis represents isolated or systemic disease. METHODS: We report 19 cases (15 consultation; 4 in-house cases) of localized testicular infarction with associated vasculitis spanning 24 years. RESULTS: All were orchiectomy specimens; detailed clinical information was available in 16 cases. Mean age was 38 years. Clinical presentation was testicular pain in 13 and mass in 3 patients. Preoperative impression was testicular cancer in 13 cases. In all cases, localized testicular infarction associated with vasculitis was present and in none was tumor identified. Most cases (n = 14) showed polyarteritis nodosa (PAN)-like features with transmural necrotizing inflammation of small-medium arteries. In 4 cases, vasculitis was granulomatous (2 necrotizing; 2 non-necrotizing) and in 1 case was lymphocytic. An infectious etiology was excluded clinically and by special stains. Four patients were subsequently confirmed with systemic vasculitis: one with PAN, one with Wegener vasculitis, one with vasculitis not otherwise specified and one with subclinical systemic vasculitis. Two of those 4 patients had testicular PAN-like vasculitis and 2 had granulomatous vasculitis. CONCLUSIONS: Testicular vasculitis can cause localized infarction that clinically mimics cancer. Although testicular vasculitis is an isolated finding in most patients an associated systemic vasculitis is not a rare event (4/16, or 25%), especially if the vasculitis is granulomatous (50% in this series). All patients should be clinically investigated for systemic disease.