Significance of adenosquamous proliferation in breast lesions.

Adenosquamous proliferation (ASP), characterised by ductal structures with a dual glandular and squamous phenotype within desmoplastic stroma, is essentially a hallmark of various sclerosing lesions of the breast (SL) and breast lesions with sclerosis (BLWS), not including sclerosing adenosis. In radial scar/complex sclerosing lesion (RS/CSL), clonality has been previously demonstrated in microdissected ASP. SL/BLWS encompass a diverse range of pathological entities that historically have an equally diverse list of names, often for histologically alike or identical lesions at different anatomical locations. In common they are comprised of one or more components of fibrocystic or proliferative breast disease and papillomata, which become distorted and even obliterated by a sclerosing process that appears to be associated with and/or secondary to ASP, which in an individual lesion may be inconspicuous at the time of biopsy. The histological overlap of various SL/BLWS with RS/CSL, in which a nidus containing ASP is pathognomonic of early lesions, also supports a common element of ASP across various SL/BLWS. SL/BLWS show an interesting association with low-grade metaplastic carcinoma, particularly low-grade adenosquamous carcinoma (LGASC) with which, they appear to form a histological and possible biological spectrum because ASP and LGASC share similar histological and immunophenotypical characteristics. The presentation of ASP in various SL/BLWS will be discussed.

Atypical presentation of oncocytic parathyroid adenoma masquerading as metastatic carcinoma.

Parathyroid carcinoma is the rarest endocrine malignancy. Definitive diagnosis is challenging as it is difficult to distinguish malignant from benign disease. A 71-year-old man presented with weight loss and hypercalcaemia. CT scans revealed multiple lung nodules and lytic bone lesions that were consistent with metastatic dissemination. Technetium-99m-sestamibi-single-photon emission computed tomography scan showed an abnormal uptake in the right thyroid lobe. Fine-needle aspiration (FNA) was performed on three occasions. The patient underwent parathyroidectomy with ipsilateral hemithyroidectomy without postoperative complications. Microscopic examination showed a parathyroid neoplasm with fibrosis and intravascular tumour on a background of unremarkable thyroid parenchyma. This resulted in an initial impression of parathyroid carcinoma. Further review by two independent pathologists provided a final diagnosis of oncocytic parathyroid adenoma. This case highlights the subjectivity and interobserver variation with endocrine histological examination. FNA can induce changes that mimic parathyroid carcinoma on histology. An index of suspicion for benign parathyroid adenomas should be maintained.

Next generation sequencing of the nidus of early (adenosquamous proliferation rich) radial sclerosing lesions of the breast reveals evidence for a neoplastic precursor lesion.

We sought to determine if adenosquamous proliferation of early cellular radial sclerosing lesions of the breast harbours hot spot mutations and to help clarify its relationship to low-grade adenosquamous carcinoma as a potential form of early neoplasia. Four low-grade adenosquamous carcinomas, early radial sclerosing lesions from 13 individuals, and 4 benign proliferative breast lesions were microdissected and assessed with a 50-gene Hot-spot cancer panel. Early radial sclerosing lesions were selectively microdissected concentrating on their adenosquamous proliferation (nidus). Hot spot mutations in PIK3CA were detected in ten (77% of) radial sclerosing lesions, in one low-grade adenosquamous carcinoma, and in usual ductal hyperplasia and apocrine adenosis. Over three quarters of individuals with cellular (adenosquamous proliferation rich) early radial sclerosing lesions tested harboured somatic mutations in PIK3CA suggesting that adenosquamous proliferation is a clonal lesion. Its relationship to low-grade adenosquamous carcinoma remains unclear in view of the small sample size and unmatched radial sclerosing lesions and low-grade adenosquamous carcinomas.

Rosai-Dorfman-type histiocytes occur in eosinophilic chronic rhinosinusitis and potentially play a role in disease initiation and persistence.

AIMS: We recently identified the presence of Rosai-Dorfman-type histiocytes (RDH) in sinonasal tissue removed from individuals with eosinophilic chronic rhinosinusitis (ECR). We sought to determine their clinical significance. METHODS AND RESULTS: Sinonasal biopsies from 10 individuals (index cases) with classical features of ECR and the additional finding of RDH were collected during a two-and-a-half-year period. Twenty-one sinonasal biopsies with a diagnosis of ECR accrued during a 6-month period were reviewed at one institution to assess the presence of this phenomenon in archived material. Five of the 10 index cases were recurrent; in four of these in which archival material was available, three had RDH on review. Of the 21 review cases, 52% contained RDH. Six of the review cases represented recurrent disease and in five of these RDH were demonstrable. Archival material was available from five cases that recurred, RDH being demonstrable in three. RDH were seen to persist across multiple recurrences. CONCLUSIONS: The presence of RDH within ECR samples is associated highly with recurrence. RDH have properties of antigen-presenting cells and may play a hitherto unrecognized role in the initiation and persistence of ECR.

An atypical presentation of small bowel obstruction and perforation secondary to sporadic synchronous intra-abdominal desmoid tumours.

INTRODUCTION: Desmoid tumours (DTs) are rare, soft tissue tumours which account for 0.03% of all neoplasms. They are characteristically locally invasive but do not metastasize. There is frequent association with females of reproductive age, a history of abdominal surgery or trauma and a family history of fibromatoses. Intra-abdominal DTs are infrequently sporadic and more commonly associated with inherited disorders such as familial adenomatous polyposis (FAP), attenuated FAP and Gardener's syndrome. PRESENTATION OF CASE: The authors report a rare case of small bowel obstruction and perforation secondary to sporadic, synchronous intra-abdominal DTs in a 54-year old man with atypical symptoms and no risk factors or family history. DISCUSSION: Intra-abdominal DTs have a worse prognosis as they can cause intestinal bleeding, obstruction and perforation. Due to the rarity of these tumours there are no clear guidelines on their management and this is instead based on small case series from specialist centres. In the non-acute setting patients with sporadic intra-abdominal DTs should be managed in a specialist sarcoma unit by a multidisciplinary team. In the presence of FAP or other polyposis syndromes patients with DTs should be managed at a specialist colorectal unit. Emergent presentations require emergency surgery in suitable candidates. CONCLUSION: In non-emergency presentations of DTs, it is essential to exclude FAP, AFAP and other hereditary polyposis syndromes since this affects treatment and subsequent follow-up.

Adenosquamous proliferation of the breast and low grade adenosquamous carcinoma: a common precursor of an uncommon cancer?

Low grade adenosquamous carcinoma (LGASC) is rare but commonly reported to arise in association with benign proliferative and sclerosing breast lesions which themselves may show associated sclerosing or 'adenosquamous proliferation' (ASP) resembling LGASC, but are often derided as reactive mimics or attributed to earlier biopsy. Among other benign lesions, radial sclerosing lesion (RSL) may be associated with LGASC, yet attention is typically focused on its relationship to more common forms of mammary carcinoma. This study aimed to assess the presence and extent of ASP in the context of RSL in a small cohort of 20 cases and its similarity to LGASC.Twenty consecutive breast excisions that had a principal or incidental diagnosis of RSL were reviewed. RSLs that displayed foci of ASP were further examined with immunohistochemical markers for p63, calponin, cytokeratin 5/6, oestrogen and progesterone receptors.Sixty percent of excisions contained ASP either associated with a RSL or a concurrent papilloma, which morphologically and immunohistochemically were indistinguishable from the neoplastic ducts of LGASC. RSL with and without ASP broadly corresponded to accepted definitions for 'early' and 'late' lesions, respectively. ASP corresponded to the characteristic compact branching ducts of the core or nidus of a RSL.The morphological and immunophenotypic similarity of the ASP found in RSL and papillomata to LGASC warrants serious consideration that they are a potential precursor to LGASC, which may most commonly involute given the rarity of clinically apparent LGASC. Further study including micro-dissection of foci of ASP to compare its molecular genetic profile to that of LGASC is required.