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Psammoma bodies in cervicovaginal cytology are a rare finding associated with malignant tumours. A 62-year-old woman was referred to our centre for cytology with nuclear atypia and psammomatous bodies suspicious of malignancy. A complete gynaecological examination was performed including colposcopy and ultrasound without significant changes. Hysteroscopy was performed to detect endometrial or endocervical malignancy, endometrial biopsy showed psammoma bodies and atrophic endometrium. Endocervical and cervical biopsies were negative for malignancy. Cervicovaginal cytology and human papillomavirus (HPV) testing were repeated. The result was suggestive of adenocarcinoma and negative for HPV. Laparoscopic hysterectomy with bilateral salpingo-oophorectomy was indicated due to two cervicovaginal cytologies with suspicion of malignancy. Low-grade peritoneal serous carcinoma was diagnosed on the surface of the uterus, ovaries and peritoneum. A second laparoscopy was performed to exclude other pelvic or abdominal lesions, and disease was found in the peritoneum of the pelvis, abdomen and omentum. Adjuvant treatment with six cycles of carboplatin and paclitaxel was indicated. Psammoma bodies in cervicovaginal cytology are a rare clinical situation, and it is mandatory to exclude malignancy.

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Papillary thyroid carcinoma (PTC) is the most common primary thyroid malignancy. PTC is diagnosed based on its hallmark nuclear characteristics, but a myriad of histological variants has been identified some of which can be diagnostically challenging due to its rarity and overlapping histomorphology with other entities. We report a rare variant of PTC with lymphoepithelial features which lacked association with Epstein-Barr Virus (EBV). In such cases, a thorough workup to rule out metastasis from other sites should be undertaken.

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Benign osseous tumors of mesodermal origin that are included within the group of fibro-osseous lesions include cemento-ossifying fibromas (COFs). The fibrocellular component of these diseases originates from the periodontal ligament, which deposits bone and cementum encased in fibrous tissue. It typically appears in the mandible and presents as a solitary, nonaggressive, slowly developing, asymptomatic, expansile lesion, rarely occurring in the maxilla. The only intervention that proved to be successful in producing excellent outcomes and that may be regarded as a final therapeutic option is the complete surgical removal of COFs. Presenting herein is a case report describing a painless and expansile mass in the left mandibular region, histopathologically diagnosed as COF.

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Pap smears play a role in detecting extrauterine serous tumours in asymptomatic women. Certain cytopathologic and histopathologic findings combined with relevant clinical and radiologic findings indicate the possibility of primary peritoneal serous tumours. Cellblock immunohistochemistry is a valuable confirmatory diagnostic tool.

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Pilocytic astrocytoma (PA), recognized as the most prevalent central nervous system (CNS) tumor, has long been associated with calcifications, a characteristic often attributed to benign or indolent growth patterns. In this study, we explored the calcified attributes in these tumors that beckon a deeper understanding. This is a retrospective study, on a set of seven cases, with a histopathological diagnosis of pilocytic astrocytoma with calcifications and psammoma bodies (PB). Despite an encouraging overall survival outcome, the recurrence in four cases cast some doubt on the conventional classification. The histological study of these cases revealed a spectrum of calcifications, varying in size and morphology, all of which exhibited positive reactivity to glial fibrillary acidic protein (GFAP), osteoconduction, and osteopontin. Notably, the immunohistochemistry showed hyaline bodies displaying an atypical immune profile, strikingly negative for vimentin and GFAP, and a robust positivity for epidermal growth factor receptors (EGFR), tumor necrosis factor-alpha (TNF-α), and interleukin 1 beta (IL-1ß). These results stimulated speculation that the identity of these calcified tumors may have extended and potentially embraced the realm of calcifying pseudoneoplasms of the neuraxis (CAPNON), underscored by intense pilot gliosis. This study transcends mere anatomical exploration; it delves into the intricacies of calcified tumors, casting a spotlight on the dynamic interplay between PA and CAPNON. As we traverse the frontiers of neuro-oncology, these findings pave the way for innovative avenues in the diagnostics and therapeutics of these tumors.

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Psammocarcinoma (PsC) represents a rare form of low-grade serous tumor of the ovary or peritoneum. Although ovarian cancer generally has a poor prognosis in its late stages, PsC seems to have a more indolent course. We present a patient with a history of unspecific abdominal pain for more than a year, with sudden acute onset of severe inguinal pain. On admission to the hospital, a computed tomography (CT) revealed a pelvic mass of suspected ovarian origin. Radical surgery was attempted but not achieved due to widespread tumor growth. Histopathological evaluation revealed estrogen receptor-positive stage III PsC. Tamoxifen treatment was thus initiated, still maintaining stable disease 10 years later. The patient has undergone extensive radiological work-up, including CT, chest X-ray, 18F-fluoro-deoxy-glucose positron emission tomography (PET)/CT, 99mTc- hydroxymethylene diphosphonate (HDP) bone scintigraphy, 18F-fluoro-thymidine (FLT) PET/CT, Tc-99m depreotide scintigraphy and magnetic resonance imaging. In conclusion, we demonstrate that PsC has characteristic radiological features and different imaging modalities can be suitable in different clinical situations. In contrast to most other ovarian cancers, PsC does not always warrant adjuvant chemotherapy, even in advanced stages. This emphasizes the need for a deeper knowledge of the biological behavior of this rare tumor, to select the optimal treatment strategy.

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The Odontogenic Keratocyst (OKC) is characterized by pathognomonic histomorphological features and rarely exhibits significant deviations. We present a case of OKC of mandibular posterior region in a 25-year-old female patient. In addition to the classical histopathological characteristics of OKC, the connective tissue near the juxta-epithelial area displayed numerous small round basophilic calcifications resembling psammomatoid ossicles. These calcifications displayed a focal distribution pattern, with round calcifications evenly spaced from each other. Some of these round calcified bodies bore a resemblance to Liesegang ring calcifications. The presence of psammomatoid ossicles in this specific OKC challenges established knowledge, emphasizing the necessity for more comprehensive investigations into these cystic variants especially related to their biological behavior.

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Ectopic calcifications are observed in many soft tissues and are associated with several diseases, including cancer. The mechanism of their formation and the correlation with disease progression are often unclear. Detailed knowledge of the chemical composition of these inorganic formations can be very helpful in better understanding their relationship with unhealthy tissue. In addition, information on microcalcifications can be very useful for early diagnosis and provide insight into prognosis. In this work the chemical composition of psammoma bodies (PBs) found in tissues of human ovarian serous tumors was examined. The analysis using Micro Fourier Transform Infrared Spectroscopy (micro-FTIR) revealed that these microcalcifications contain amorphous calcium carbonate phosphate. Moreover, some PB grains showed the presence of phospholipids. This interesting result corroborates the proposed formation mechanism reported in many studies according to which ovarian cancer cells switch to a calcifying phenotype by inducing the deposition of calcifications. In addition, other techniques as X-ray Fluorescence Spectroscopy (XRF), Inductively Coupled Plasma Optical Emission Spectroscopy(ICP-OES) and Scanning electron microscopy (SEM) with Energy Dispersive X-ray Spectroscopy (EDX) were performed on the PBs from ovary tissues to determine the elements present. The PBs found in ovarian serous cancer showed a composition comparable to PBs isolated from papillary thyroid. Based on the chemical similarity of IR spectra, using micro-FTIR spectroscopy combined with multivariate analysis, an automatic recognition method was constructed. With this prediction model it was possible to identify PBs microcalcifications in tissues of both ovarian cancers, regardless of tumor grade, and thyroid cancer with high sensitivity. Such approach could become a valuable tool for routine macrocalcification detection because it eliminates sample staining, and the subjectivity of conventional histopathological analysis.

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Prostate cancer is a heterogeneous disease with several well-recognized morphologic subtypes and histologic variants-subsets of which are enriched for or associated with specific genomic alterations. Herein, we report a cohort of 4 unique prostate cancers characterized by intratumoral psammomatous calcification-which we have termed prostate cancer with psammomatous calcification (PCWPC). Clinicopathologic review demonstrates that PCWPCs are high-grade (grade group ≥3) tumors that involve the anterior prostate, and integrative targeted next-generation sequencing reveals recurrent hotspot IDH1 mutations. This morphology-molecular correlation is independently confirmed in The Cancer Genome Atlas prostatic adenocarcinoma cohort, with 3 of the 5 IDH1-mutant prostate cancers showing psammomatous calcification (rφ = 0.67; Fisher exact test, P < .0001). Overall, these findings suggest that PCWPC represents a novel subtype of prostate cancer enriched for an anterior location and the presence of hotspot IDH1 mutations. Recognition of these unique morphologic features could help identify IDH1-mutant prostate cancer cases retrospectively and prospectively-facilitating future large research studies and enabling clinical trial enrollment and precision medicine approaches for patients with advanced and/or aggressive disease.

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AIMS: Renal cell carcinoma (RCC) with clear cells and psammoma-like calcifications would often raise suspicion for MITF family translocation RCC. However, we have rarely encountered tumours consistent with clear cell RCC that contain focal psammomatous calcifications. METHODS AND RESULTS: We identified clear cell RCCs with psammomatous calcifications from multiple institutions and performed immunohistochemistry and fluorescence and RNA in-situ hybridisation (FISH and RNA ISH). Twenty-one tumours were identified: 12 men, nine women, aged 45-83 years. Tumour size was 2.3-14.0 cm (median = 6.75 cm). Nucleolar grade was 3 (n = 14), 2 (n = 4) or 4 (n = 3). In addition to clear cell pattern, morphology included eosinophilic (n = 12), syncytial giant cell (n = 4), rhabdoid (n = 2), branched glandular (n = 1), early spindle cell (n = 1) and poorly differentiated components (n = 1). Labelling for CA9 was usually 80-100% of the tumour cells (n = 17 of 21), but was sometimes decreased in areas of eosinophilic cells (n = 4). All (19 of 19) were positive for CD10. Most (19 of 20) were positive for AMACR (variable staining = 20-100%). Staining was negative for keratin 7, although four showed rare positive cells (four of 20). Results were negative for cathepsin K (none of 19), melan A (none of 17), HMB45 (none of 17), TFE3 (none of 5), TRIM63 RNA ISH (none of 13), and TFE3 (none of 19) and TFEB rearrangements (none of 12). Seven of 19 (37%) showed chromosome 3p deletion. One (one of 19) showed trisomy 7 and 17 without papillary features. CONCLUSIONS: Psammomatous calcifications in RCC with a clear cell pattern suggests a diagnosis of MITF family translocation RCC; however, psammomatous calcifications can rarely be found in true clear cell RCC.

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The detection of psammoma bodies (PBs) in the thyroid gland is commonly associated to classic papillary thyroid carcinoma (PTC) and are frequently encountered in differnt subtypes of PTCs. Nonetheless, the evidence of PBs without a PTC may represent a diagnostic challenge. The general statement is that PBs represent a metastatic finding of PTC either when encountered inside the thyroid parenchyma or in the perithyroidal lymph nodes. The majority of authors assess that in presence of PBs, a search for an occult PTC is strongly encouraged and mandatory, especially if a lobectomy had been performed. In fact, it is not uncommon that a contralateral or ipsilateral tumor, mostly PTC, is found leading to the suggestion that the best recommendation is to submit the entire thyroid tissue. Nonetheless, when a cancer has not been found, the possibility of the rare evenience that PBs are likely to be associated with benign conditions should be considered among the differential diagnosis. Herein a short commentary and review of the literature on PBs detection and its diagnosis, based on our recent experience.

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Melanotic schwannoma (MS) is a rare peripheral nerve sheath tumor commonly found in the thoracic paraspinal region. It is present in an intracranial location rarely, with 18 out of 105 MS cases described in the literature. Trigeminal nerve was involved in only six of these cases. Fifty percent of psammomatous melanotic schwannoma (PMS) patients have Carney complex. Carney complex is an autosomal dominant disorder featuring peripheral nerve tumors (schwannomas), myxomas (heart, skin, and breast), skin pigmentation (lentigines and blue nevi), and endocrine tumors (adrenal, testicular, and pituitary). We present a case of left trigeminal nerve PMS as a part of Carney complex. Patient had diffuse lentiginosis. Magnetic Resonance Imaging revealed enhancing lesion along left trigeminal nerve with widened Meckel's cave and foramen ovale. Final diagnosis of PMS was derived on clinical, radiological, and histopathological findings with immunohistochemistry correlation. Key Message Trigeminal nerve can be rarely involved in melanotic schwannoma (MS). Knowledge of typical radiological features of MS is crucial for its diagnosis. Its association with Carney complex should be sought.

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Objective: Cervical lymph node metastasis (LNM) was found to be clinically significant prognostic factors of patients with papillary thyroid carcinomas (PTC). Ultrasound (US) characteristics of thyroid nodules and thyroid parenchyma may be used to predict LNM. To investigate the value of nodular US features as well as thyroid parenchymal microcalcifications on US in predicting LNM in patients with PTC. Methods: This prospective study was approved by the Institutional Review Board. From January 2018 to June 2019, 971 consecutive patients with solitary PTC who underwent preoperative neck US evaluation were included from six hospitals in China. The US features of thyroid nodules as well as thyroid parenchyma microcalcifications were carefully evaluated based on the static images and dynamic clips. Univariate and multivariate analyses were performed to determine independent predictors of LNM. Results: Of the 971 patients, 760 were female, 211 were male. According to the pathological examination, 241(24.82%) patients were found with cervical LNM (LNM positive group), while 730 (75.18%) patients were not (LNM negative group). Multiple logistic regression analysis showed that young age (<55 years old) (OR = 1.522, P = 0.047), large size (>10 mm) (OR = 1.814, P < 0.001), intratumoral microcalcifications (OR = 1.782, P = 0.002) and thyroid parenchyma microcalcifications (OR = 1.635, P = 0.046) were independent risk factors for LNM of PTC. Conclusions: Young age, large nodule size, intratumoral microcalcifications, as well as thyroid parenchyma microcalcifications on US are independent predictors of cervical LNM for patients with PTC.

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BACKGROUND: Pelvic washing specimens are relatively common and are submitted for patients undergoing gynecologic surgery to evaluate them for metastatic or occult disease. Psammoma bodies are a relatively uncommon finding in these specimens. To date, large-scale studies of their cytologic-histologic correlates and thus clinical significance have been limited. METHODS: A 10-year retrospective search for all pelvic washing specimens was performed, and all cases were reviewed for the presence of psammoma bodies. The findings for the corresponding surgical pathology specimens were then catalogued. RESULTS: Psammoma bodies were present in 138 cases (3.6% of 3840 total pelvic washings). More than half of the cases (n = 73 [53%]) were associated with benign processes, including mesothelial hyperplasia (n = 44), endosalpingiosis (n = 11), endometriosis (n = 11), and ovarian cystadenoma/cystadenofibroma (n = 7). Nineteen cases (14%) were associated with serous borderline tumors. Malignancies were noted in a third of the cases (n = 46 [33%]) and were most frequently low-grade serous adenocarcinomas (n = 15), high-grade serous adenocarcinomas (n = 11), or endometrioid endometrial carcinomas (n = 8). Patients found to have benign processes (median age, 50 years) or borderline disease (median age, 56 years) were significantly younger than patients with malignancies (median age, 65 years; P < .0001). In addition, the correlation of cytologic interpretation categories with concurrent histopathologic findings showed that cytologic analysis was highly sensitive and specific in determining the nature of underlying processes. CONCLUSIONS: The majority of psammoma bodies noted in pelvic washings were associated with benign processes or borderline tumors, with approximately a third of the cases associated with malignancies. Psammoma bodies in pelvic washings from younger patients were significantly more likely to be associated with benign processes or borderline tumors.

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Biomineralization of skeletal components (e.g., bone and teeth) is generally accepted to occur under strict cellular regulation, leading to mineral-organic composites with hierarchical structures and properties optimized for their designated function. Such cellular regulation includes promoting mineralization at desired sites as well as inhibiting mineralization in soft tissues and other undesirable locations. In contrast, pathological mineralization, with potentially harmful health effects, can occur as a result of tissue or metabolic abnormalities, disease, or implantation of certain biomaterials. This progress report defines mineralization pathway components and identifies the commonalities (and differences) between physiological (e.g., bone remodeling) and pathological calcification formation pathways, based, in part, upon the extent of cellular control within the system. These concepts are discussed in representative examples of calcium phosphate-based pathological mineralization in cancer (breast, thyroid, ovarian, and meningioma) and in cardiovascular disease. In-depth mechanistic understanding of pathological mineralization requires utilizing state-of-the-art materials science imaging and characterization techniques, focusing not only on the final deposits, but also on the earlier stages of crystal nucleation, growth, and aggregation. Such mechanistic understanding will further enable the use of pathological calcifications in diagnosis and prognosis, as well as possibly provide insights into preventative treatments for detrimental mineralization in disease.

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Melanotic schwannoma is a rare form of nerve sheath tumor composed of melanin-producing neoplastic Schwann cells. Less than 200 cases have been reported worldwide. The entity has been associated with Carney complex, a rare genetic disorder characterized by multiple benign tumors. A 38-year-old female presented to our unit with sudden-onset lower back pain and radiculopathy triggered by a mechanical injury. Imaging demonstrated a lesion within the left L5/S1 neural exit foramen with remodeling of bony architecture typical of a chronic, benign process. She proceeded for resection and histology revealed a psammomatous melanotic schwannoma. The patient recovered well with improvement in symptomology. Due to the aggressive nature of the disease, she remains under surveillance for local recurrence and distant metastasis. Clinicians should be aware of this malignant entity, despite its possible presentation with radiological features of a chronic, benign process. Unusual characteristics such as hemorrhage should be treated with a high index of suspicion.

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In thyroid cancer, calcification is mainly present in classical papillary thyroid carcinoma (PTC) and in medullary thyroid carcinoma (MTC), despite being described in benign lesions and in other subtypes of thyroid carcinomas. Thyroid calcifications are classified according to their diameter and location. At ultrasonography, microcalcifications appear as hyperechoic spots ≤ 1 mm in diameter and can be named as stromal calcification, bone formation, or psammoma bodies (PBs), whereas calcifications > 1 mm are macrocalcifications. The mechanism of their formation is still poorly understood. Microcalcifications are generally accepted as a reliable indicator of malignancy as they mostly represent PBs. In order to progress in terms of the understanding of the mechanisms behind calcification occurring in thyroid tumors in general, and in PTC in particular, we decided to use histopathology as the basis of the possible cellular and molecular mechanisms of calcification formation in thyroid cancer. We explored the involvement of molecules such as runt-related transcription factor-2 (Runx-2), osteonectin/secreted protein acidic and rich in cysteine (SPARC), alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteopontin (OPN) in the formation of calcification. The present review offers a novel insight into the mechanisms underlying the development of calcification in thyroid cancer.

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Calcification in lung nodules usually indicates a benign lesion. Here, we report the case of a 59-year-old male patient with a well defined 30 mm calcified nodule in his right upper lung lobe and calcified mediastinal lymph nodes. The mass was diagnosed as adenocarcinoma by transbronchial biopsy. He received systemic chemotherapy, followed by lobectomy and mediastinal lymph node dissection. During surgery, the lymph nodes were tightly adherent to the superior vena cava with invasion of the vascular wall. Pathological diagnosis confirmed acinar adenocarcinoma and psammoma bodies (PBs). Immunohistochemical analysis revealed tumor cells positive for parathyroid hormone-related proteins 1 and 2. Calcification of primary lung adenocarcinoma is rare. We report a calcified lesion where the secretion of parathyroid hormone by the tumor may have caused the accumulation of PBs. Calcification of metastatic lymph nodes may increase the risk of adhesion, requiring care during surgery. KEY POINTS: Significant findings of the study Lung adenocarcinoma with extensive calcification in primary and metastatic lymph node lesions is rare and the mechanism involved is poorly understood. Of significance, calcification in our case was related to parathyroid hormone-related proteins 1 and 2 secreted by the tumor. What this study adds This study suggests the potential role of parathyroid hormone-related proteins in lung tumor calcification. The implications for clinicians are that calcified metastatic lymph nodes and tumors might be tightly fused to tissues. Therefore, surgery should be conducted with care.

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Recently the knowledge of chemical composition of pathological mineralizations is an important topic extensively studied because it could give more in-depth information to understand pathologies themselves and to improve prevention methods. In this work, psammoma bodies (PBs) microcalcifications in thyroid cancer tissue are investigated by different and complementary analytical methods as: micro-Fourier transformed spectroscopy, X-ray fluorescence spectroscopy, Inductively Coupled plasma Optical Emission Spectroscopy (ICP-OES) and scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy imaging (EDX). For the first time the micro-FTIR analysis of the only inorganic phase isolated from PBs was reported. Signals of the recorded spectrum showed that the main component of the calcifications is the amorphous carbonated calcium phosphate, and the IR spectrum of thyroid PBs is strongly consistent with that of PBs in human ovarian tumors. The XRF and the ICP analysis detected also the presence of iron ad zinc in thyroid PBs. These results are validated by scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy imaging (EDX) carried out on tissue samples of the papillary thyroid carcinoma. By these analytical methods magnesium and sodium were detected within PBs while the presence of iron was confirmed by the Perls test. Summarizing the results of applied analytical methods, the main detected elements within the thyroid psammoma bodies are Ca, P, Mg, Na, Fe and Zn. Magnesium and sodium are found in malignant breast cancer microcalcifications, thus they seem correlated to neoplastic transformation. The Fe and Zn elements could give information about the origin of these pathological microcalcifications.

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Benign endometrial calcifications with or without bone fragments are uncommon clinicopathologic findings. They can be detected during pelvic ultrasonography or as incidental pathologic findings. They have been found to be associated with infertility and menstrual anomalies in young adult patients and in symptomatic postmenopausal women with endometrial atrophy and endometrial polyps. Its exact etiology is unknown, its pathogenesis is controversial, and its clinical importance is not fully validated. We performed a retrospective review study over 7 years and found 11 (0.4%) cases of benign endometrial calcifications. The mean patient age was 45.2 years (range = 20-66 years). All of the women complained of menstrual abnormalities and 4 complained of infertility. Six had a previous procedure of abortion, 2 had oral contraceptive pills, and 4 a course of progesterone therapy. Their size and morphology varied from heterogeneous microcalcifications of variable appearances, shattered glassy chunks to detached bones. Four cases were associated with endometrial polyps, 1 with a placental site nodule, 1 with chronic endometritis, and 1 with endometrial hyperplasia. Most showed secretory endometrial tissue and ciliated cell metaplasia. Two cases showed atrophic endometrium. Etiology and pathogenesis are multifactorial and miscellaneous. Progesterone may play a role. Heterogeneous histomorphologic patterns may carry potential pitfalls. Pathologic recognition is clinically important to reassure clinicians in symptomatic postmenopausal women, alert gynecologists to a treatable albeit rare cause of infertility in younger women, and assist in patients' counselling. We also included cases of calcifications associated with endometrial malignancies to compare and contrast malignant endometrial calcifications with benign endometrial calcifications.

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