Spinal calcifying pseudoneoplasm of the neuraxis (CAPNON) associated with facet joint pathologies: CAPNON diagnostic and pathogenic insights.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumor-like fibro-osseous lesion that can develop anywhere in the neuraxis. Approximately a half of reported CAPNONs developed in the spinal region, mostly close to the facet joint (FJ). The diagnosis of spinal CAPNONs is challenging given the existence of mimics and associated pathologies including calcific degeneration of the FJ ligaments (DFJL) and synovial cysts (SCs). The pathogenesis of CAPNON remains elusive, although there have been a few hypotheses including degenerative, reactive, proliferative and immune-mediated processes. Our present study examined clinical, radiological and pathological features of 12 spinal CAPNONs in comparison to 9 DFJL foci, and diagnostic and pathogenic relationship between CAPNONs and FJ pathologies. On imaging, CAPNONs were all tumor-like and typically bigger than DFJL foci. All CAPNONs showed pathologically diagnostic features including characteristic cores, consistently identifiable core-surrounding/peripheral palisading of macrophages and other cells including multinucleated giant cells, variable infiltration of CD8+ T-cells, and multifocal immunopositivity of neurofilament light chain (NF-L). These features were absent or limited in the DFJL foci with statistically significant differences from CAPNONs, except calcifications. Spinal CAPNONs co-existed with DFJL foci in all cases; some had transitional foci with overlapping focal CAPNON and DFJL-like features. These findings, along with our previously reported relationship between CAPNONs and SCs, suggest that spinal CAPNONs may occur in association with or in transition from calcifying/calcified degenerative lesions of FJ ligaments and/or SCs when a reactive proliferative process is complemented by other pathogenic changes such as immune-mediated pathology and NF-L deposition/expression.

Rheumatoid nodules: a narrative review of histopathological progression and diagnostic consideration.

Rheumatoid nodules (RNs) are the most common extra-articular manifestation of rheumatoid arthritis and are also seen in patients with other autoimmune and inflammatory diseases. The development of RNs includes histopathological stages of acute unspecified inflammation, granulomatous inflammation with no or minimal necrosis, necrobiotic granulomas typically with central fibrinoid necrosis surrounded by palisading epithelioid macrophages and other cells, and likely an advanced stage of "ghost" lesions containing cystic or calcifying/calcified areas. In this article, we review RN pathogenesis, histopathological features in different stages, diagnostically related clinical manifestations, as well as diagnosis and differential diagnosis of RNs with an in-depth discussion about challenges in distinguishing RNs from their mimics. While the pathogenesis of RN formation remains elusive, it is hypothesized that some RNs with dystrophic calcification may be in transition and may be in coexistence or collision with another lesion in patients with RA or other soft tissue diseases and comorbidities. The diagnosis of typical or mature RNs in usual locations can be readily made by clinical findings often with classic RN histopathology, but in many cases, particularly with atypical or immature RNs and/or unusual locations, the clinical and histopathological diagnosis can be challenging requiring extensive examination of the lesional tissue with histological and immunohistochemical markers to identify unusual RNs in the clinical context or other lesions that may be coexisting with classic RNs. Proper diagnosis of RNs is critical for appropriate treatment of patients with RA or other autoimmune and inflammatory diseases.

Spinal calcifying pseudoneoplasm of the neuraxis (CAPNON) and CAPNON-like lesions: CAPNON overlapping with calcified synovial cysts.

Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare tumour-like fibro-osseous lesion in the neuraxis including the spine. It is diagnosed by the presence of the following histological features: granular amorphous to chondromyxoid fibrillary cores with calcification/ossification, peripheral palisading of spindle to epithelioid cells, variable fibrous stroma, and foreign body reaction with multinucleated giant cells, as well as positive NF-L immunostaining. Spinal CAPNON is sometimes named as tumoural calcinosis that is tumour-like dystrophic calcification usually in the periarticular tissue and also described in calcified synovial cyst (CSC). We examined clinical, radiological and pathological features of five spinal CAPNONs and 21 spinal CSCs including three recurrent lesions. The results demonstrated some radiological and pathological overlaps between these two entities, as well as distinct features of each entity to be diagnosed. All CAPNONs showed the diagnostic histological features with NF-L positivity mainly in lesion cores and variable CD8+ T-cells. In contrast, CSCs exhibited the synovial lining and variable degenerative/reactive changes with some CAPNON-like features, but mostly no to occasionally limited NF-L positivity and less CD8+ T-cells with statistically significant differences between groups of CAPNONs and CSCs. Four CSCs contained CAPNON-like foci with the CAPNON diagnostic features including prominent NF-L positivity, and some transitional features from CSC to CAPNON. As the pathogenesis of CAPNON is likely reactive/degenerative in association with an inflammatory/immunological process involving NF-L protein deposition, our findings suggest the link between spinal CAPNON and CSC, with possible transition from CSC to CAPNON or CAPNON developing in reaction to CSC.

Variation in breast cancer grading in 1,636 resections assessed using control charts and in silico kappa.

OBJECTIVE: Assess interpretative variation in Nottingham grading using control charts (CCs) and in silico kappa (ISK). METHODS: In house invasive breast cancer cases (2011-2019) at two institutions with a synoptic report were extracted. Pathologist interpretative rates (PIRs) were calculated and normed for Nottingham grade (G) and its components (tubular score (TS), nuclear score (NS), mitotic score (MS)) for pathologists interpreting >35 cases. ISKs were calculated using the ordered mutually exclusive category assumption (OMECA) and maximal categorical overlap assumption (MCOA). RESULTS: The study period included 1,994 resections. Ten pathologists each assessed 38-441 cases and together saw 1,636; these were further analyzed. The PIR medians (normed ranges) were: G1:24%(18-27%), G2:53%(43-56%) and G3:26%(19-33%). The MCOA ISK and the number of statistical outliers (p< 0.05/p< 0.001) to the group median interpretive rate (GMIR) for the ten pathologists was G1: 0.82(2/0 of 10), G2: 0.76(1/1), G3: 0.71(3/1), TS1: 0.79(1/0), TS2: 0.63(5/1), TS3: 0.66(5/1), NS1: 0.37(5/4), NS2: 0.60(4/3), NS3: 0.59(4/4), MS1: 0.78(3/1), MS2: 0.78(3/1), MS3: 0.77(2/0). The OMECA ISK was 0.62, 0.49, 0.69 and 0.71 for TS, NS, MS and G. CONCLUSIONS: The nuclear score has the most outliers. NS1 appears to be inconsistently used. ISK mirrors trends in conventional kappa studies. CCs and ISK allow insight into interpretive variation and may be essential for the next generation in quality.

Reactive Nodular Fibrous Pseudotumor Mimicking Metastatic Gastrointestinal Stromal Tumor to Perigastric Lymph Node: A Case Report and Review of the Literature.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal lesions of the gastrointestinal tract. Many are treated surgically with or without the use of adjuvant tyrosine kinase inhibitors. Metastases to lymph nodes are infrequent. In this article, we present a case of a perigastric nodule presenting 3 years postsurgical treatment for biopsy-proven GIST, clinically suspicious for a recurrent/metastatic GIST. The patient had also received adjuvant tyrosine kinase inhibitor therapy. Microscopic sections from the perigastric lesion showed a spindle cell nodule felt initially to represent a GIST with posttherapeutic changes. Together with morphology, immunohistochemical workup supported the myofibroblastic origin of the spindle cells, consistent with a reactive nodular fibrous pseudotumor, and definitively excluded metastatic GIST. This case highlights an important diagnostic pitfall and is the first known case of a GIST preceding a reactive nodular fibrous pseudotumor.