International Journal of Surgical Pathology

Aims. To identify the most common reasons for consultation to a large specialty breast pathology service at a major institution. To provide insight into the overall challenges in practicing breast pathology. Methods. The anatomic pathology database at one institution was searched for all breast consultations received in 2021, excluding in-house patients and patients who were transferring care. Results. A total of 553 patients met the criteria (n = 553) from a variety of academic and private practices. For each patient, the paperwork from the submitting institution was reviewed to identify the specific question, and subsequently classified into 14 categories. The reason for the consultation request was not provided for 78 (14%) patients, and a review of the outside diagnoses, where applicable, was performed. In summary, the top 5 reasons for consultation were: (1) assistance with classification of atypical intraductal epithelial proliferations (32%); (2) evaluation for the presence of (micro-)invasive carcinoma (14%); (3) evaluation of fibroepithelial (12%), (4) papillary (11%), and (5) spindle cell lesions (7%). Conclusion. We show an ongoing educational and practice gap for pathologists who most commonly struggle with classifying atypical precursor lesions, specifically when these are small and focal, or bordering on intraductal carcinoma (32%, 177/553). The second most common reason for consultation was classifying invasive carcinomas as microinvasive and subtypes (total of 20.4%, 113/553). As such, our data supports the continued need for rigid and clear criteria for diagnosing threshold lesions (namely atypical hyperplasias) and intraductal carcinoma of the breast.

The diagnosis of primary leiomyosarcoma (LMS) of bone is generally established based on integrative findings of morphologic features, immunohistochemical staining, and clinical and radiological findings. There are no specific genetic alterations that can be used to confirm the diagnosis of LMS in challenging diagnoses of bone sarcomas with myogenic differentiation. In this study, we assessed the utility of a DNA methylation-based classifier as an ancillary diagnostic tool for subclassifying bone sarcomas with myogenic differentiation. DNA methylation profiling using the Deutsches Krebsforschungszentrum classifier system was performed on 5 patients with available formalin-fixed paraffin-embedded tissue blocks. The original diagnosis of LMS was retained in 2 of 5 patients. Three patients were reclassified as having malignant giant cell tumor of the bone, malignant peripheral nerve sheath tumor, or undifferentiated pleomorphic sarcoma/myxofibrosarcoma after integrating the results of the DNA methylation-based classifier with the clinicopathologic, immunohistochemical, and radiologic findings. While a DNA methylation-based classifier can serve as a useful ancillary tool for refining the subclassification of primary bone sarcomas with myogenic differentiation, especially for diagnostically challenging tumors, integrating clinical, histopathological, and radiological findings is essential for obtaining a final diagnosis.

Objectives. To determine the accuracy of grading pancreatic well-differentiated neuroendocrine tumors (PanNETs) on endoscopic ultrasound-guided fine needle biopsy (EUS-FNB). Methods. Fifty-three (53) PanNETs from 52 patients with EUS-FNB and subsequent resection were included, including 1 patient with 2 synchronous tumors biopsied separately. Grade (G) was assigned as per the 2019 World Health Organization criteria. The concordance of grade between EUS-FNB and resection was measured using kappa statistic. Clinicopathologic features were compared between specimens with concordant or discordant grading. Results. Two-thirds of patients were male, and the median age was 62 years (range 27–85). Four received neoadjuvant therapy. 89% were nonfunctional, whereas 11% were functional. Concordance of grade between EUS-FNB and resection was moderate (kappa = 0.45). Precisely 25% (13 out of 51) of G1 or G2 specimens were discordant. G2 tumors were frequently undergraded on EUS-FNB (11 out of 18; 61%), whereas G1 tumors were only rarely overgraded (2 out of 33; 6%). Two G3 tumors were concordant. There was no correlation between concordance and other clinicopathologic features, except for perineural invasion. Conclusions. The concordance of PanNET grading between EUS-FNB and resection was moderate, and G2 tumors were frequently undergraded on EUS-FNB. Knowledge of this is important to recognize and acknowledge, as this could potentially impact treatment decisions in some patients.

IgG4-related disease (IgG4-RD) is an autoimmune disease of unknown cause. RUNX1 is a transcription factor involved in immune responses, and its dysfunction leads to uncontrolled immune responses. We performed, to our knowledge, the first RUNX1 methylation analysis in type 1 autoimmune pancreatitis (denoted simply as AIP), a representative IgG4-RD. We conducted methylation array analysis on AIP samples using the Illumina Infinium MethylationEPIC array. We identified a potentially important RUNX1 methylation abnormality in AIP, which was further confirmed using the quantitative SYBR green methylation-specific polymerase chain reaction (QSG-MSP) method. Using immunohistochemistry, we analyzed RUNX1 expression in lymphocytes in 11 lymph nodes with AIP (LN-AIP) and 20 lymph nodes with pancreatic ductal adenocarcinoma (PDA; LN-PDA). LN-AIP and LN-PDA refer to lymph nodes from patients with AIP and PDA, respectively. All selected PDA patients lacked lymph node metastases. By array analysis, RUNX1 was more highly methylated in LN-AIP than in LN-PDA (P = 0.0275). RUNX1 was also more highly methylated in LN-AIP than in LN-PDA by QSG-MSP validation (P = 0.0331). Immunohistochemical analysis indicated that RUNX1 expression was significantly lower in LN-AIP than in LN-PDA (P = 0.0250). Aberrant RUNX1 methylation and reduced expression may be characteristic of AIP. Further validation is warranted.

Background. Metastasis of alveolar soft part sarcoma (ASPS) to the adrenal gland is infrequent, with only eight patients reported in the literature. Here we present an ASPS in an adolescent girl presented as a hypervascular adrenal incidentaloma along with a review of the available literature. This study aims to serve as a reference to aid in the pre-operative radiological and histopathological diagnosis of this rare entity. Case presentation. A 17-year-old adolescent girl presented to the Department of Urology after the detection of a hypervascular left adrenal incidentaloma on follow-up PET-CT, five months post-surgery for frontal bone ASPS. The radiological differential diagnoses were adrenocortical carcinoma, pheochromocytoma, and metastatic ASPS. The post-operative adrenalectomy specimen, on gross examination, revealed a solid, variegated tumor replacing the entire normal adrenal parenchyma. Haematoxylin and eosin-stained sections showed a tumor with cells dispersed in nests separated by large fibrovascular septae. The tumor cells were large, polygonal with abundant clear to eosinophilic cytoplasm and prominent nucleoli. Occasional mitotic figures, foci of necrosis, dystrophic calcification, and sinusoidal and vascular invasion were noted. Histopathological differential diagnoses were metastatic ASPS, a primary adrenocortical carcinoma, and local infiltration/metastases from renal cell carcinoma. Ancillary studies including immunohistochemistry, fluorescent in situ hybridization (FISH), and ultrastructural examination helped to confirm the diagnosis of alveolar soft part sarcoma metastatic to the adrenal gland. Conclusion. ASPS presenting as a hypervascular incidentaloma is rare and is likely to be misdiagnosed, especially as adrenocortical carcinoma, pheochromocytoma, and renal cell carcinoma. The differential diagnosis is further complicated by an overlap of pathological features among these entities. A relevant clinical history and ancillary tests are mandatory to diagnose these tumors. Early detection can help timely therapeutic intervention that can improve patient outcome.

Objective. The presence of high tumor budding in colorectal carcinomas is a significant pathological feature indicative of a high potential for lymph node metastasis. Our aim was to investigate the prognostic impact of tumor budding in ampullary carcinomas. Materials and methods. We conducted a cohort of 101 consecutive ampullary carcinoma resections to evaluate tumor budding, macroscopic and microscopic subtypes, lymphatic/vascular/perineural invasions, and other histopathological parameters. Results. High tumor budding was observed in 49 (49%) of the tumors, and multivariate survival analysis evaluating the overall survival of these patients found tumor budding to be an independent poor prognostic indicator (p = 0.013). Conclusion. Tumor budding should be reported in ampullary carcinomas as it serves as an independent predictor of a poor outcome.

Mesonephric-like adenocarcinoma (MLA) is a newly recognized type of carcinoma that occurs in the uterus and ovaries. MLA exhibits distinct morphological and immunophenotypical features similar to those of mesonephric carcinoma of the cervix or vagina, with the majority of reported tumors containing KRAS mutations. MLA is exceedingly rare and appears to be associated with aggressive clinical behavior. Literature regarding the clinical behavior of MLAs remains limited. Here, we report four additional MLA patients with detailed morphological and immunophenotypical analysis, as well as clinicopathological and follow-up information. Additionally, molecular study was conducted on the ovarian MLA tumor and one uterine MLA tumor. Our findings support the observation that MLA is associated with an aggressive clinical course and poor clinical outcomes. Out of four tumors presented, 2 (50%) were at an advanced clinical stage, 3 (75%) presented with metastasis (including 2 (50%) with lung metastasis), and 2 (50%) patients died of the disease. MLA is often misdiagnosed as other types of gynecological carcinoma, as indicated in the literature and evidenced in our study, where 2 (50%) were initially misdiagnosed as low-grade endometrioid carcinoma in biopsy. Therefore, an integrated approach, including careful evaluation of the morphological and immunophenotypical features of the tumor, preferably with molecular confirmation, is critical for accurate diagnosis of this aggressive malignancy.

Lung adenocarcinomas often contain multiple histological components. This study discusses the role of minor components in the progression of the disease. A retrospective evaluation was conducted on 108 patients with lung adenocarcinoma who underwent surgery at our center between 2013 and 2018, with tumor sizes less than 3 cm. The patients were categorized into four groups based on the presence of lepidic (L) and micropapillary/solid (MP/S) patterns at a minimum threshold of 5% (“L+, MP/S-”, “L+, MP/S+”, “L–, MP/S–”, “L-, MP/S+”). The groups were compared in terms of standard uptake value, pleural invasion, lymphovascular invasion, perineural invasion, spread through air spaces, N1-N2 station lymph node metastasis, recurrence, and survival. No tumors of perineural invasion, spread through air spaces, or lymph node metastasis was observed in the “L+, MP/S–“ group, and lymphovascular invasion was found to be significantly lower compared to other groups (p = 0.040). The standard uptake value levels in groups containing the lepidic pattern were significantly lower than in other groups (p = 0.006). The time to recurrence in the “L+, MP/S–“ group was 121.5 ± 10.9 months, with a median survival time of 110.9 ± 10.6 months, which was longer compared to the other groups (86.2 ± 5.9 and 77 ± 13.4 months). In lung adenocarcinomas, prognosis estimation should be based not only on the dominant component but also on the presence of histological components such as lepidic and micropapillary/solid, even if they are minor.

The proliferation of recognized neoplasms related to related to rearrangements involving kinase genes, arising in diverse somatic tissue lineages, poses an increasing challenge in surgical pathology. For instance, ALK rearrangements have been observed in diverse neoplasms of epithelial, connective tissue, and hematolymphoid lineages, many of which are associated with overexpression of ALK by immunohistochemistry as a useful biomarker. An even higher order challenge and pitfall would be the scenario where a tumor without an ALK rearrangement nonetheless overexpresses the protein, thereby simulating an ALK-defined neoplasm. Herein, we present this exact scenario, where an angiomatoid fibrous histiocytoma, exhibiting the recently-described phenomenon of its overexpression of ALK, clinically, histologically, and immunophenotypically simulated ALK-positive histiocytosis.

Nodular fasciitis is a benign, usually self-limiting myofibroblastic proliferation with a predilection for the upper extremities, trunk, and head and neck, and almost all of which harbor the USP6::MYH9 fusion. Since nodular fasciitis is not widely recognized to arise within the joints, it may therefore cause diagnostic confusion in this uncommon setting. We report an unusual tumor of an 11-year-old patient who presented with a 6-month history of right elbow swelling and pain. Histology revealed that the tumor was composed solely of proliferating bland spindle cells with osteoclast-like giant cells and scattered foam cells. There was only a focal area of immature granulation-like myxoid change, which suggested nodular fasciitis. Molecular analysis using next-generation sequencing revealed gene rearrangement involving USP6 and MYH9, supporting the diagnosis of nodular fasciitis within the elbow joint. This is the first of intraarticular nodular fasciitis within the elbow joint in which USP6::MYH9 gene fusion was identified by molecular analysis.

Intrahepatic cholangiocarcinoma is a primary liver malignancy with poor prognosis and limited treatment options. Lymphoepithelioma-like intrahepatic cholangiocarcinoma is an exceedingly rare variant of intrahepatic cholangiocarcinoma that histologically resembles nasopharyngeal carcinoma, previously known as lymphoepithelioma. It was first reported by Hsu et al in 1996 and they were able to show the presence of Epstein-Barr virus in tumor cells. Even though several risk factors for the development of intrahepatic cholangiocarcinoma have been identified, the association between Epstein-Barr virus and intrahepatic cholangiocarcinoma is relatively rare. This article aims at discussing a female patient's lymphoepithelioma-like intrahepatic cholangiocarcinoma tumor and summarizing the existing literature on Epstein-Barr virus-positiveLymphoepithelioma-like intrahepatic cholangiocarcinoma, including the clinical features, pathogenesis, diagnostic challenges, treatment approaches, prognosis, and histopathologic description.

Hemosiderotic fibrolipomatous tumor (HFLT) and myxoinflammatory fibroblastic sarcoma (MIFS) are rare, locally aggressive soft tissue tumors with a predilection for distal extremities of middle-aged adults. Hybrid tumors (HFLT-MIFS) demonstrate overlapping features of both and share recurrent translocation (1;10) (p22; q24). We describe a tumor with high-grade sarcomatous transformation of a hybrid HFLT-MIFS, with a novel ADAMTS12::TERT gene fusion, presenting as a right foot soft tissue mass in an 85-year-old woman. Histologically, the tumor showed a high-grade sarcoma with areas of hybrid HFLT-MIFS in subsequent resection. The patient was treated surgically with a below-knee amputation and interval radiation therapy. On RNA-based next-generation sequencing, the tumor harbored a novel ADAMTS12::TERT gene fusion. In addition to reporting a novel gene fusion in a rare example of hybrid HFLT-MIFS with high-grade sarcomatous transformation, we also discuss relevant morphological features of sarcomatous HFLT and provide a brief review of reported neoplasms with TERT gene fusions.

Primary intracranial sarcoma, DICER1-mutant, included as a new diagnostic entity in the 2021 WHO Classification of Central Nervous System Tumors, is a rare, but aggressive neoplasm generally identified in the supratentorial forebrain. The prognostic implications of these uncommon tumors and optimal treatment strategy remain unclear. A 19-year-old woman was found unresponsive after reporting a severe headache. CT demonstrated an intra-axial, mass-like hemorrhage in the left temporal lobe which was subsequently resected. A review of the electronic medical record, histologic characterization by hematoxylin and eosin-stained sections and a targeted panel of immunohistochemical stains, and molecular characterization was pursued. The tumor was pleomorphic and demonstrated varying cellularity. The tumor cells had hyperchromatic nuclei with a spindled to round appearance. Numerous mitoses, interspersed islands of mature hyaline cartilage, and scattered eosinophilic globules associated with cells with marked nuclear atypia were noted. The tumor cells were positive for desmin, myogenin, and SMSA (focal) and negative for other lineage markers, suggestive of a mesenchymal neoplasm with myogenic differentiation. Next-generation sequencing revealed DICER1 (E1705K and P1805fs) and KRAS (Q61H) variants; the composite methylation profile prompted a final diagnosis of primary intracranial sarcoma, DICER1-mutant. This lesion underscores the histologic and immunophenotypic variability of these rare tumors. Notable features include prominent cartilaginous islands, retained H3K27me3 expression, prominent expression of desmin, and the presence of the unique DICER1 P1805fs variant, which has not previously been reported in this tumor type. We compile the molecular and immunohistochemical findings of all primary intracranial sarcomas, DICER1-mutant to date.

Secretory carcinoma is a rare breast tumor driven by ETV6::NTRK3 fusion. It has characteristic morphologic features and identification of these tumors is critical as these patients may benefit from TRK inhibitors. Morphologic shift upon treatment has not been reported in secretory carcinoma or other NTRK-driven tumors. Herein we describe a patient with secretory carcinoma showing transdifferentiation into metaplastic carcinoma (spindle cell and squamous cell carcinoma) at the metastatic site following treatment. Identification of these morphologic shifts is crucial for accurate classification and identification of potential resistant mechanisms.

Combined ganglioneuroma-schwannoma is an exceedingly rare tumor that has only been described in isolated case reports. We document a 64-year-old man with an incidentally discovered combined ganglioneuroma-schwannoma of the retroperitoneum that was intimately associated with sympathetic ganglia. We highlight the morphological and immunohistochemical findings of this rare tumor, and show evidence of its origin from sympathetic ganglia.

Although more than 90% of pancreatic tumors represent primary tumors, specifically ductal adenocarcinomas, metastatic tumors are not infrequent at this site. Metastasis of salivary gland tumors to the pancreas is exceedingly rare, with only a few cases reported in the English-language medical literature. Here, we report a patient with metastatic adenoid cystic carcinoma to the pancreas, 24 months following the initial diagnosis, and review the available literature on secondary tumors located in the pancreas with an emphasis on tumors of salivary gland origin.

Isocitrate dehydrogenase (IDH) mutant gliomas are classified as astrocytoma or oligodendroglioma based on the recent application of ATRX mutation, TP53 mutation, and 1p/19q co-deletion. Astrocytomas classically show ATRX and TP53 mutations, whereas oligodendrogliomas are defined by 1p/19q co-deletion. However, there are reports of gliomas that harbor both astrocytoma and oligodendroglioma morphologically and molecularly. Here we present a patient of a 29-year-old woman who presented with a headache and underwent gross total excision. Magnetic resonance imaging showed a right frontal space-occupying lesion with T2 fluid-attenuated inversion recovery mismatch. Histology showed 2 distinct areas of morphology compatible with oligodendroglioma and astrocytoma. Immunohistochemistry showed both components being positive for IDH R132H. Alpha thalassemia/mental retardation syndrome X-linked (ATRX) showed loss of nuclear expression and p53 was strongly positive in the morphologic astrocytoma component, whereas ATRX was retained and p53 was negative in the morphologic oligodendroglioma component. Fluorescence in situ hybridization showed 1p/19q co-deletion in the oligodendroglioma component while co-deletion was absent in the astrocytoma component. TERT mutation was present in the oligodendroglioma component, whereas it was absent in the astrocytoma component. Although rare, gliomas harboring both oligodendroglioma and astrocytoma components in a single tumor exist and show genetically distinct areas.

Fibromatosis-like metaplastic carcinoma (FLMC) is a rare subtype of metaplastic carcinoma of the breast. Diagnosing this entity poses significant challenges, particularly in core biopsies due to limited sampling and overlap with benign spindle cell lesions such as nodular fasciitis and fibromatosis. We present an example of FLMC in an asymptomatic middle-aged woman. As her breast imaging revealed an irregular lobulated mass, a core biopsy was performed which showed benign breast tissue with fibrosis. However, this was discordant with her imaging findings, hence a subsequent vacuum-assisted biopsy was done which revealed low-grade spindle cell proliferation, consistent with FLMC. This report emphasizes the necessity of a triple assessment and highlights the potential pitfalls in diagnosing FLMC, particularly the risk of misinterpretation due to its histological similarities with benign entities. Understanding these challenges will be crucial to avoid diagnostic delays of this rare breast cancer subtype.

Mammary-like anogenital glands are considered a normal constituent of the anogenital area. These glands can have epithelial components with eccrine or apocrine features. They often undergo transformation into mammary-like lesions, including lactational changes that occur during pregnancy and the breastfeeding period. When they form mass lesions they are referred to as lactating adenomas. Their appearance can clinically be mistaken for other more common benign and malignant entities in the vulva. We describe a vulvar lesion in a 26-year-old woman. The lesion was excised and determined by histologic examination to be a benign lactating adenoma. Subsequent immunohistochemistry was performed. The epithelial cells were positive for GATA3 and estrogen receptor while negative for PAX8, supporting mammary-like differentiation. The myoepithelial markers p63 and calponin were positive at the periphery of the ducts, supporting the benign nature of this lesion.

Isolated osseous involvement without lymphadenopathy is a rare manifestation of Rosai-Dorfman disease. It clinically and radiologically mimics infections and primary bone tumors. The present report describes a 9-year-old girl with multifocal monomelic osseous involvement as an isolated manifestation. She presented with lytic lesions in the left proximal phalanx of the great toe and head of the second metatarsal unaccompanied by disease elsewhere. She was treated outside as chronic osteomyelitis. After 9 months, the swelling recurred, and a repeat biopsy was suggestive of Rosai-Dorfman disease. This report highlights the diagnostic challenges in patients with extra nodal isolated bone involvement, especially on small biopsies.

Smooth muscle and adenoma-like renal tumor (SMART) is a biphasic tumor composed of cytologically bland stromal and epithelial components. It has many histopathological mimickers. A 57-year-old man presented with a left renal mass. The left radical nephrectomy showed a 13.5 cm tumor involving the entire kidney. The microscopic examination showed an unencapsulated, well-circumscribed biphasic tumor composed predominantly of intersecting bundles of smooth muscle, admixed with focal epithelial components arranged in cystic, tubular, tubulopapillary, nests, and cords. Both the components lacked nuclear atypia. Using immunohistochemistry, the spindle cells were positive for SMA and desmin, focally positive for CD10, and negative for ER, PR, and HMB45. The epithelial cells were positive for PAX8 and keratin 7 and negative for CD10. We report an additional example of SMART with a literature review. Knowledge about this recently described entity would lead to a better understanding of the clinicopathological features and histogenesis of this tumor.

The persistence of fetal vitelline structures may occur. The primary intestinal arterial supply development happens normally in this scenario, but a vitelline vascular remnant (VVR) persists. A 13-year-old boy with a history of severe and intermittent abdominal pain since early infancy presented to the Emergency Department with clinical, analytical, and ultrasonographic findings suggestive of acute appendicitis. There was no evidence of intestinal obstruction. Surgical treatment was indicated. A thick fibrovascular band from the umbilicus to the terminal ileum's mesentery was identified during laparoscopy. A gangrenous cecal appendix was also identified. A regular appendectomy and surgical excision of the band was performed. The histopathological study confirmed that it was a persistent right vitelline artery (VVR) and that the patient had acute gangrenous appendicitis. The patient evolved favorably and is currently asymptomatic and under follow-up. The literature on VVR is scarce. The present manuscript reviews the main characteristics of this embryological insult based on the preceding literature. Standardization of terminology regarding VVR will help better understand this pathology in the future.

NR1D1::MAML1/L2 fusion-positive sarcomas constitute an emerging subtype of undifferentiated sarcomas, histopathologically composed of epithelioid and spindle cells. We describe two NR1D1exon6::MAML2exon2 fusion-positive sarcomas occurring in the occipital region of a 53-year-old female patient and the left shoulder of a 25-year-old male patient. Histopathologically, the former tumor comprised spindle and polygonal-shaped/epithelioid cells, while the latter comprised epithelioid cells. Immunohistochemically, the cells of the first tumor were positive for keratin cocktail (AE1/AE3), EMA, and p40. The other tumor lacked any epithelial marker immunoexpression and showed SATB2 positivity. Both the tumors were SMARCB1 proficient. While the former tumor was initially diagnosed as a sarcomatoid carcinoma, the latter was diagnosed as an undifferentiated sarcoma. Both patients underwent surgical resection as the primary treatment. One patient received adjuvant radiotherapy, whereas the other received ifosfamide and doxorubicin-based therapy. However, both the patients developed progressive disease, with one developing lung metastasis during relapse. There was a suboptimal response to chemotherapy in both patients. This study highlights the clinicopathological features of two rare and emerging sarcomas. It further emphasizes the value of high-throughput molecular testing, such as next-generation sequencing in the undifferentiated epithelioid, and spindle-cell sarcomas to identify the prognostic subtypes and differentiate these neoplasms from their histopathological mimics.

DEK::AFF2 squamous cell carcinoma is a recently recognized entity characterized by a non-viral-related non-keratinizing squamous cell carcinoma with chromosomal rearrangement between DEK on 6p22.3 and AFF2 on Xq28. This neoplasm is associated with an aggressive clinical behavior, particularly regarding local recurrences and distant metastases even with its deceptively bland histomorphology. In this article, we report on 2 patients with DEK::AFF2 squamous cell carcinomas, which were only diagnosed at the time of recurrence. Patient #1 was originally misdiagnosed with inverted papilloma. This occurred 3 years previously, and at second presentation the tumor was recurrent in the nasal cavity and paranasal sinuses. Patient #2 was identified at second recurrence of a “nasopharyngeal carcinoma,” initially diagnosed in the nasopharynx 5 years earlier, with a subsequent recurrence in the middle ear 2 years later, involving the mastoid process. The immunophenotypic and molecular work-up, as well as the management of these patients, are discussed. In our review of the English-language literature on DEK::AFF2 squamous cell carcinomas, we identified 41 patients, including our 2 patients. Of these, 26 had information on their clinical course. Sixty-nine percent of patients reported a history of locoregional recurrence, and 19% reported a history of distant metastases, with an average follow-up duration of 36 months after multimodality therapies. Given our improved understanding of DEK::AFF2 squamous cell carcinoma as an aggressive tumor, it is crucial to differentiate this neoplasm from other potential histomorphologic mimickers to ensure early and accurate diagnosis.

Keratin positive giant cell rich tumor is a rare mesenchymal tumor first described in 2020. It can occur in both soft tissue and bone and predominantly affects young women. The tumor's biological behavior remains uncertain despite its low-grade classification. Characterized by keratin expression and a HMGA2::NCOR2 gene fusion, keratin positive giant cell rich tumors resemble conventional giant cell tumors but lacks H3-3A gene mutations. This article presents a 31-year-old woman with a keratin positive giant cell rich tumor in the pelvic bone, detailing her clinical presentation, diagnostic process, treatment, and postoperative recovery. Histological examination revealed numerous osteoclast-like giant cells within a mononuclear stroma, with RNA sequencing confirming the HMGA2::NCOR2 fusion. The patient's management included surgical resection, with no recurrence at six months follow-up. The discussion emphasizes the need for further research to understand keratin positive giant cell rich tumors pathogenesis and explore potential targeted therapies.

Osteoid osteoma is a benign bone tumor commonly affecting young individuals, with a rare occurrence in older adults. It typically presents with night pain relieved by nonsteroidal anti-inflammatory drugs and is characterized radiographically by a small, radiolucent nidus surrounded by reactive sclerosis. We present a 70-year-old female patient with persistent right hip pain, initially diagnosed as arthritis, who underwent total hip arthroplasty. Preoperative imaging findings were inconclusive, showing edema and degenerative changes without a definitive lesion. Histopathological examination of the arthroplasty specimen revealed a nodule consistent with osteoid osteoma. This report highlights the diagnostic challenge of osteoid osteoma in elderly patients, where symptoms may be atypical and overlap with other conditions like osteoarthritis.

Median mandibular cyst is defined as an odontogenic cyst in a rare midline location. In spite of this definition, there have been two reports of a peculiar lesion, so-called “ciliated” median mandibular cyst associated with vital teeth, the origin of which cannot be explained in terms of odontogenic epithelium multipotentiality. We describe a thorough profile of an additional example. On the basis of the cone-beam computed tomography images of a wide open cavity in the midline of the lingual bone, the surgical findings of no association with the vital incisor roots, the immunophenotypes of the excretory duct epithelium and the absence of oncogenic mutations, the present “ciliated” median mandibular cyst associated with vital teeth may be an artifact caused by impingement of the lingual bone due to pedicled extension from an extra-glandular salivary duct cyst in the anterior mouth floor. Awareness of this ectopic presentation is of clinical importance for the differential diagnosis of radiolucencies in the median mandible.

STK11 adnexal tumors are recently named tumors of the female adnexal region, associated with Peutz-Jeghers syndrome (PJS). There is a lack of studies on the clinical phenotypes of PJS concerning the pathology and molecular characteristics of STK11 adnexal tumors. We searched for 781 relevant studies through PubMed and Web of Science, and preliminary statistical and grouping comparisons were made using the screened study data combined with our patient. A total of 25 patients with STK11 adnexal tumors (excluding tumors with no detectable STK11 alterations) were reported in 4 studies. The tumors were most common in middle-aged women (mean age of 39 years) and typically located at paratubal sites (76%). Nearly half of patients (45%) had PJS manifestations or molecular changes. Compared with sporadic (non-PJS) STK11 adnexal tumors, PJS-associated STK11 adnexal tumors were slightly larger in diameter (mean 12.6 cm vs 8.9 cm) and had a longer interval between first recurrences (median 19 months vs 7 months). Primary tumors with pelvic recurrence had a reduced keratin 7 positive rate and tended to grow in non-paratubal sites. However, overall, the clinicopathological characteristics of PJS-associated tumors and sporadic tumors were similar, as was the immunohistochemical expression of primary and recurrent tumors. More specimens and studies are needed to support these observations and further delineate the characteristics of STK11 adnexal tumors.

Phaeohyphomycotic agents causing central nervous system (CNS) infection is rare and is known to affect immunocompetent individuals. We present a patient with a CNS phaeohyphomycotic abscess that had developed within a temporal lobe glioma. Magnetic resonance imaging (MRI) performed two months prior to the surgery showed only the presence of a neoplasm. However, a repeat MRI in the immediate pre-operative period revealed an additional, likely fungal, lesion. During this interval of 2 months, the patient had received a short course of steroids for suspected encephalitis. The steroid therapy and the CNS tropism of the fungi could have contributed to the CNS mycosis. The intratumoral localization of the fungi could be attributed either to the altered tumour vasculature or to a mere coincidence. Occurrence of CNS mycosis within a high grade glioma is exceedingly rare. A majority of such patients reported in the literature had received chemotherapy for the glioma.

Merkel cell carcinoma (MCC) is an uncommon aggressive neoplasm, usually arising in sun-exposed skin of the head and neck. By immunohistochemistry, KRT20 and MCPyV positivity are found in about 90% and 80% of MCCs, respectively. Noteworthy, viral status in lip/oral cavity MCCs is poorly known. A 78-year-old male was referred presenting a tumor mass on the right maxilla four months ago. Computed tomography revealed an extensive osteolytic lesion in the right maxillary sinus extending into the orbit and nasal cavity and crossing the midline. Microscopy revealed large necrotic areas admixed by sheets of small, round cells with hyperchromatic nuclei exhibiting a '“salt and pepper” chromatin pattern, which showed immunopositivity for pan-KRT AE1/AE3, EMA, CD56, CD99 (weak), CD138, S100 (focal), vimentin (focal), synaptophysin, FLI1, INSM1, MCPyV, SATB2, and Ki-67 (MKI67 [40%]). Moreover, intact RB1 and wild-type p53 expression were observed. Relevantly, KRT20, KRT5/6, chromogranin A, p40, p63, HMB45, NF, TTF1, TDT (DNTT), PAX5, p16, KIT, as well as high-risk HPV and EBER1/2 (both by ISH), were negative. This report illustrates that a detailed immunohistochemical study, including STAB2 and MCPyV markers, as well as a careful clinical workup, are essential to adequately classify high-grade neuroendocrine carcinomas, especially KRT20-negative MCC.

Extra-skeletal Ewing sarcoma is a rare tumor, most commonly occurring in the paravertebral region, extremities, retroperitoneum, and very rarely in visceral locations. We present two primary visceral Ewing sarcomas confirmed at the molecular level: one located in the stomach and the other in the bladder. Both tumors demonstrated strong and diffuse membranous CD99 expression, accompanied by variable KIT immunoreactivity. Additionally, we provide a review of the literature on primary gastric and bladder ES, including an analysis of differential diagnoses for gastric and bladder tumors exhibiting CD99 and KIT expression.