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BACKGROUND: Currently the clinicopathologic significance of psammoma bodies in cytology specimens are not completely understood, including types of cytology specimens and pathologic conditions frequently associated with this unique cytologic feature. In this study, we undertook a retrospective approach to review the specimen types, cytology preparations, patient characteristics, organs or tissues involved and differential diagnoses in cytology specimens with the finding of psammoma bodies. METHODS: Cytology cases with the finding of psammoma bodies from January 2004 to December 2022 were retrieved from our institution's pathology databases, and their clinicopathological features were reviewed. RESULTS: A total of 78 cytology specimens with the finding of psammoma bodies were recorded in our CoPath system. The mean age at diagnosis was 59 years. The patient group showed female gender predominancy (90%). FNA specimens comprised about 38.5% of total cases. Other common specimen types were body cavity fluids (38.5%), including pleural effusion and peritoneal fluid, and about 20.5% of the cases were pelvic washing performed during gynecologic surgeries. Most cytology cases with psammoma bodies had a malignant diagnosis (69%). About 18% of the cases were in the indeterminate diagnostic categories, with 12% suspicious for malignancy and 6% of the cases with atypical cells. About 5% of cases were placed in the neoplastic category, while 8% of cases were negative for malignancy. About 79% of peritoneal cytology with psammoma bodies were neoplastic and mostly gynecologic tumors. Pleural fluids with psammoma bodies were very likely to be malignant and involved by serous carcinoma (15 of 16 cases, 94%). Papillary thyroid carcinoma was the second most common malignancy in our series, present in about 53% of thyroid cytologies with the finding of psammoma bodies. CONCLUSION: Our study showed that psammoma bodies in cytology preparations were more often associated with malignancies in our study of 78 cytology specimens (69%). The most sampled location in our study was peritoneal cavity, followed by pleural cavity, thyroid, lymph nodes, neck masses, and omentum. The clinicopathologic value of psammoma bodies in predicting malignancy varies depending on locations and specimen types.

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Odontogenic keratocysts (OKCs) are locally aggressive cysts that exhibit typical histopathological features and have a propensity for recurrence. Though histological variations are observed in OKCs, hard tissue formation and metaplastic changes are rare, and the underlying pathogenesis is not well understood. This study aimed to characterize stromal calcifications and analyze their association with odontogenic components in non-syndromic and syndrome-associated cases of OKCs. We analyzed 153 cases of OKCs from healthcare institutes in India and Japan. The epithelial and stromal features were evaluated, and the relationship of calcifications with odontogenic rests was determined. Immunohistochemistry for cytokeratin-19 and special stains including Masson Trichrome and Van Gieson, were used for identification of odontogenic rests and calcifications respectively. Stromal calcifications were observed in 29.41% OKCs. The calcification patterns included irregular dystrophic, dentinoid with linear or calcospherite-type mineralization, and psammoma calcifications. Psammoma and dentinoid calcifications were found in the proximity of cytokeratin-19-positive odontogenic rests or satellite cysts, whereas majority cases with dystrophic calcifications did not exhibit co-localization with stromal odontogenic components. Distinct patterns of calcifications were observed in OKCs. Calcifications found in proximity of the odontogenic rests were possibly indicative of an inductive or host-mediated response.

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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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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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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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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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Tenosynovitis with psammomatous calcifications is a rare condition primarily affecting female patients in the distal extremities. This case report presents a unique instance of tenosynovitis with psammomatous calcification in a 31-year-old man presenting with wrist pain. Initial misdiagnosis and unsuccessful steroid injections prompted further investigation, leading to the discovery of an extra-articular calcified mass. Arthroscopic resection was attempted but found to be unnecessary because the lesion was located outside the joint. Histopathological examination confirmed the diagnosis of tenosynovitis with psammomatous calcification. After mass removal, the patient experienced relief from wrist pain and resumed work within a month. Subsequent follow-ups at 9 months showed no recurrence of pain, with full range of wrist motion and no grip power weakness. This case highlights the importance of differentiating tenosynovitis with psammomatous calcification from intra-articular lesions, particularly in atypical presentations, and demonstrates the effectiveness of surgical intervention in resolving symptoms.

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Objective: Punctate echogenic foci (PEF)/microcalcifications are thought to represent psammoma bodies (PB) in histopathology. However, there are few and contradictory data on this. Different types of sonographic echogenic microfoci (EMF) are seen in papillary thyroid carcinoma (PTC), and their histopathological equivalents are not clearly known. There is also conflicting data on the interobserver agreement between the sonographers on EMF. Methods: We prospectively collected US video records of PTC nodules with and without EMF in two large thyroid centers. All video recordings were independently interpreted by three blinded, experienced sonographers. EMF were classified as true microcalcifications (punctate echogenic foci (PEF) ≤1 mm long), linear microechogenities (>1 mm long, posterior acoustic enhancement of the back wall of a microcystic area), comet-tail artifacts/reverberations or linear microechogenities with comet-tail artifacts/reverberations, non-shadowing coarse echogenic foci (>1 mm nonlinear areas) and unclassifiable. Histopathological evaluation was performed by two blinded, qualified pathologists. Results: A total of 114 malignant nodules were included. The average Cohen's kappa (κ) of three sonographers for the EMF presence was 0.775, indicating substantial agreement. A substantial agreement for PEF with 0.658 κ, only fair agreement for other types of EMF with 0.052 to 0.296 κ were detected. EMF were significantly associated with PB and papillae. PEF had an evident relationship with PB in multivariate analysis. There was a strong positive correlation between the amount of PEF and PB (r = 0.634, P < 0.001). Conclusions: PEF in PTC mainly correspond to PB on histopathology. Although observation of EMF varies among sonographers, this inconsistency can be reduced by classifying EMF into subgroups and keeping the term 'PEF' only for true microcalcifications.

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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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Concentric calcifications, also known as psammoma bodies, are a relatively frequent finding in certain types of tumors, particularly papillary thyroid carcinoma (PTC). In the thyroid, they have been assigned a significant role in the diagnosis of PTC and in distinguishing between these tumors and other types of thyroid neoplasms. Concentric calcifications have also less commonly been noted in other processes in the thyroid, such as in tumors characterized by cells containing abundant oxyphilic cytoplasm (i.e., Hürthle cells). We have studied 12 patients with oncocytic thyroid follicular tumors that contained scattered psammomatous calcifications that led to difficulties in diagnosis. The patients were 9 women and 3 men, aged 34 to 63 years. 10 cases corresponded to benign, non-invasive oncocytic tumors and 2 cases were minimally invasive follicular carcinomas of oncocytic (so called Hürthle cell) type. The psammomatous calcifications were randomly scattered throughout the lesions and were present as a focal, incidental finding in 8 cases and were diffuse in 4 cases. They were composed of concentrically laminated deposits of dense basophilic material closely resembling psammoma bodies, often associated with more homogeneous deposits of lightly eosinophilic material without concentric lamination that were interpreted as precipitated thyroglobulin. Seven patients with clinical follow-up, including one with minimally invasive carcinoma, were alive and well between 5 and 12 years after diagnosis. Concentric laminated calcifications may be encountered in oncocytic (Hürthle cell) follicular tumors and should not be interpreted as indicative of PTC in the context of oncocytic neoplasms of the thyroid.

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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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A unique subtype of biphasic renal cell carcinoma (RCC) was recently described and termed biphasic hyalinizing psammomatous RCC (BHPRCC). This tumor shows a dual population of larger cells and small cells surrounding basement membrane-like materials and invariably has papillary features, hyalinized stroma, and psammoma calcifications. The biphasic pattern in BHPRCC may resemble that of RCC associated with TFEB gene fusion or t (6;11) RCC. However, all reported BHPRCCs had no TFEB alterations and all were associated with neurofibromin 2 (NF2) mutations. Herein, we present three biphasic RCCs encompassing the reported BHPRCC morphologies. One RCC showed solid, nested, papillary, and tubular growths, with biphasic pattern of larger cells surrounding clusters of smaller cells arranged around basement membrane-like materials, and harbored NF2 mutation consistent with BHPRCC. This patient developed bone metastasis 59 months after surgery. The two other biphasic RCCs showed morphologic overlap to BHPRCC, but in addition had other features not seen in BHPRCC, such as lack of papillary pattern, having large tubules containing mucinous to collagenous spherules (mucicarmine and collagen IV positive) bordered by a single layer of small cells with occasional central targetoid psammoma bodies, and with widespread nuclear grooves. Interestingly, these two tumors also did not show alterations in NF2 or TFEB including translocation or amplification. In conclusion, we report another example of the novel BHPRCC that had metastasized and two biphasic RCCs not associated with NF2 or TFEB alterations; the latter two shared additional distinct morphological features and may represent a unique biphasic RCC distinct from the novel BHPRCC.

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The consistency of spinal meningiomas is important to consider when performing tumor removal surgery. This study evaluated the correlations between spinal meningioma consistency and both preoperative computed tomography (CT) values and histopathological subtypes. Fifteen consecutive patients who underwent surgical resection of spinal meningioma at our institution were identified, and preoperative CT values and the signal intensity of T2-weighted magnetic resonance images of the tumor were determined retrospectively. The consistency of the spinal meningioma was defined based on the ultrasonic surgical aspirator output during tumor debulking. Patients were assigned to 2 groups: a soft group (n=4) and a hard group (n=11). The T2 signal intensity was significantly higher in the soft group than in the hard group (p=0.001). While the CT values were considerably higher in the hard group, the difference was not significant (p=0.19). Regarding the histopathological subtypes, psammomatous meningioma exhibited significantly higher CT values than meningothelial meningioma (p=0.019); however, there was a higher frequency of hard tumors in meningothelial meningioma cases than in psammomatous meningioma cases. Although neither robust correlations between tumor consistency and CT values nor a relationship between tumor consistency and histopathological subtype has been established, these results might help with the perioperative manegement of spinal tumors.

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PURPOSE: To quantify calcification in spinal meningiomas using Hounsfield unit (HU) values on CT, and to analyze the characteristics of cases with and without calcification and with different histologic subtypes. METHODS: The subjects were 53 patients who underwent surgical resection of spinal meningioma between January 1999 and December 2019. Clinical and surgical data were collected, and all patients were examined neurologically preoperatively and at final follow-up using the modified McCormick scale and the American Spinal Injury Association scale. Calcification was quantified on CT of the spine prior to surgery. A HU value >60 was considered to indicate calcification. RESULTS: The 53 patients (11 males, 42 females) were aged 62.4 ± 14.3 (range 19 to 91) years at surgery, and had a symptom duration of 10.8 ± 9.0 (1-36) months. The histological type was meningothelial in 35 cases, psammomatous in 13, and others in 5. The mean tumor volume was 1166 ± 350 (593-2176) mm3, and the mean HU value was 212.2 ± 192.8 (43-648). Forty cases (75%) had calcification (HU value > 60). HU values were significantly related to duration of symptoms (R = 0.590, p < 0.05) and significantly higher in psammomatous cases (p < 0.05). Cases with calcification had longer operative times and greater blood loss, and a significantly lower rate of neurological improvement. CONCLUSION: CT was effective for detecting calcification based on HU values. Detection of a HU value > 60 in spinal meningioma may be useful to narrow the differential diagnosis, evaluate the difficulty of resection, and improve intraoperative management, all of which may improve outcomes.

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