Dysplastic follicular dendritic cells in hyaline-vascular Castleman disease: a rare occurrence creating diagnostic difficulty.

Follicular dendritic cell (FDC) proliferations and dysplastic FDCs can be seen in Hyaline-vascular Castleman disease (HVCD). The association between HVCD and FDC sarcoma is well-documented; dysplastic FDCs may be precursors to FDC sarcoma. Herein, we describe a case of HVCD with strikingly large and dysplastic FDCs, which raised the differential of Hodgkin lymphoma and other neoplasms. Scattered dysplastic FDCs were predominantly in germinal centers and mantle zones, and rarely in interfollicular areas. Although occasional germinal centers contained increased FDCs, no mass forming proliferations were present to suggest FDC sarcoma. Immunostaining demonstrated that the atypical FDCs expressed CD21, clusterin and CXCL13, but not CD23, S100, pankeratin or CD30; they aberrantly expressed epidermal growth factor receptor (EGFR). The present case demonstrates that dysplastic FDCs may be present as isolated cells that require immunophenotyping to distinguish them from malignant entities with similar morphologic features. A variety of FDC markers is required to confirm their origin as the expression of any single marker is not assured, as occurred in this case. Pathologists need be aware of FDC proliferations in HVCD because of their association with FDC sarcoma. Aberrant EGFR expression by dysplastic FDCs may indicate that they are pre-neoplastic and necessitate long-term patient follow-up.

Atypical apocrine adenosis of the breast: long-term follow-up in 37 patients.

CONTEXT: Atypical apocrine adenosis is a rare breast lesion in which the cellular population demonstrates cytologic alterations that may be confused with malignancy. The clinical significance and management of atypical apocrine adenosis are unclear because of the lack of long-term follow-up studies. OBJECTIVE: To determine the breast cancer risk in a retrospective series of patients with atypical apocrine adenosis diagnosed in otherwise benign, breast excisional biopsies. DESIGN: We identified 37 atypical apocrine adenosis cases in the Mayo Benign Breast Disease Cohort (9340 women) between 1967 and 1991 with a blinded pathology rereview. Breast cancer diagnoses subsequent to initial atypical apocrine adenosis biopsy were identified (average follow-up, 14 years). RESULTS: The mean age at diagnosis of atypical apocrine adenosis in the group was 59 years. Breast carcinoma subsequently developed in 3 women (8%) with atypical apocrine adenosis, diagnosed after follow-up intervals of 4, 12, and 18 years. The tumor from 1 of the 3 cases (33%) was ductal carcinoma in situ, contralateral to the original biopsy, and the other 2 cases (66%) were invasive carcinoma. Ages at the time of diagnosis of atypical apocrine adenosis were 55, 47, and 63 years for those that developed in situ or invasive carcinoma. CONCLUSIONS: (1) Atypical apocrine adenosis was a rare lesion during the accrual era of our cohort (<1% of cases); (2) women found to have atypical apocrine adenosis were, on average, older than were other patients with benign breast disease, however, there does not seem to be an association with age and risk for developing carcinoma in patients diagnosed with atypical apocrine adenosis, as previously suggested; and (3) atypical apocrine adenosis does not appear to be an aggressive lesion and should not be regarded as a direct histologic precursor to breast carcinoma.

ALK-1 protein expression and ALK gene rearrangements aid in the diagnosis of inflammatory myofibroblastic tumors of the female genital tract.

CONTEXT: Inflammatory myofibroblastic tumor is a predominantly benign, spindle cell, mesenchymal neoplasm with myxoid areas that occurs rarely in the female genital tract and may be confused with other spindle cell lesions, particularly leiomyosarcoma. OBJECTIVE: To investigate the utility of detecting anaplastic lymphoma kinase-1 protein expression and ALK gene rearrangements in the diagnosis of inflammatory myofibroblastic tumors in the female genital tract. DESIGN: Eight inflammatory myofibroblastic tumors arising in the female genital tract and seen in consultation (from 2004 to 2011) were reviewed. Immunohistochemistry for anaplastic lymphoma kinase-1 and fluorescence in-situ hybridization studies for ALK gene rearrangements were performed. RESULTS: The anatomic sites included myometrium (4 cases) and endometrium, fallopian tube, cervix, and a cervical polyp (1 each), with a patient age range from 25 to 52 years. Histologic features ranged from bland spindle cells to striking cytologic atypia, embedded in a prominent myxoid background. Anaplastic lymphoma kinase-1 immunohistochemistry was positive in 7 cases. Fluorescence in-situ hybridization studies detected ALK gene rearrangements in 5 cases. Five cases had both immunopositivity and fluorescence in-situ hybridization abnormalities, 2 cases had immunopositivity only, and 1 case was negative by both methods. CONCLUSIONS: This is the first report, to our knowledge, of ALK gene rearrangements in inflammatory myofibroblastic tumors in the female genital tract. If a myxoid background is appreciated in a spindle cell lesion of the female genital tract, especially if inflammatory cells are present, anaplastic lymphoma kinase-1 staining along with fluorescence in situ hybridization studies, for ALK gene rearrangements, may aid in distinguishing inflammatory myofibroblastic tumors from their malignant mimics.

Presence of c-KIT-positive mast cells in obliterative bronchiolitis from diverse causes.

CONTEXT: The mechanism of fibrosis is not clear in patients with obliterative bronchiolitis after a remote injury. Immune-mediated progression may be a reason. c-KIT (CD117)-positive mast cells have been associated with chronic fibrosing diseases and may potentially be treated with imatinib (Gleevec), a c-KIT blocker. OBJECTIVE: To evaluate the role of mast cells in fibrosis associated with obliterative bronchiolitis. DESIGN: Four cases of obliterative bronchiolitis (household cleaner exposure, ammonia exposure, idiopathic, and posttransplantation) were compared with asthma/emphysema. Small and large airways were stained for CD20, CD3, CD4, CD8, CD117, CD34, CD25, stem cell factor (c-KIT ligand) and with toluidine blue, hematoxylin-eosin, and trichrome. c-KIT (CD117)-stained slides were digitally scanned with Aperio ScanScope and stained cells within the epithelium and subepithelium of small and large airways were counted (per millimeter of basement membrane). RESULTS: Mast cells were concentrated within the involved subepithelium of small airways in obliterative bronchiolitis (122 cells/mm), unlike asthma/emphysema (25 cells/mm). Conversely, there were more mast cells in the epithelium in cases of asthma/emphysema than in obliterative bronchiolitis (7 cells/mm and 2 cells/mm, respectively). Mast cells were significantly increased around involved airways versus uninvolved airways (52 cells/mm vs 14 cells/mm). Large airways in either group had similar c-KIT (CD117) expression. Stem cell factor was not increased. CONCLUSIONS: Mast cells appear to be concentrated in the lesional small-airway subepithelium in obliterative bronchiolitis. The possible role of c-KIT inhibitors such as imatinib (Gleevec) in the progression of fibrosis preceding the development of obliterative bronchiolitis is discussed.