Cytologic Atypia Research Articles

Primary Intraosseous Solitary Fibrous Tumor of the Mandible: Report of a Diagnostically Challenging Case with NAB2::STAT6 Fusion and Review of the Literature.

Solitary fibrous tumor (SFT) represents an uncommon mesenchymal neoplasm affecting primarily the extremities and deep soft tissues with, overall, benign but locally aggressive biologic behavior and an underlying pathognomonic NAB2::STAT6 fusion. Intraosseous SFTs are infrequent, and involvement of the jawbones is exceedingly rare. A 54-year-old woman presented with an asymptomatic, well-demarcated, multilocular radiolucency of the left posterior mandible featuring focally irregular borders, root resorption and lingual cortex perforation. The lesion had shown progressive growth over a 6-year period. Microscopically, a proliferation of predominantly ovoid and spindle-shaped cells with indistinct cell membrane borders, elongated, plump or tapered, hyperchromatic nuclei, and lightly eosinophilic cytoplasm was noted. Marked cytologic atypia, pleomorphism and mitoses were absent. A secondary population of epithelioid cells exhibiting ovoid or elongated vesicular nuclei, and abundant, pale eosinophilic or vacuolated cytoplasm was also present. The supporting stroma was densely fibrous with areas of marked hyalinization and variably-sized, ramifying, thin-walled vessels. By immunohistochemistry, lesional cells were strongly and diffusely positive for STAT6 and CD99, and focally immunoreactive for MDM2 and SATB2. Ki-67 was expressed in less than 5% of lesional cells, while most interspersed epithelioid cells were positive for the histiocyte marker, CD163. Molecular analysis disclosed a NAB2::STAT6 fusion confirming the diagnosis of SFT. The patient underwent segmental mandibulectomy. Herein, we report the first case of primary intraosseous SFT of the mandible with complete documentation of its characteristic immunohistochemical and molecular features. Diagnosis of such unusual presentations may be further complicated by the challenging histomorphologic diversity of SFT.

Clear cell stromal tumor of the lung: Report of 3 cases with emphasis on multifocal tumors.

We describe 3 patients with clear cell stromal tumor (CCST) of the lung, all of whom presented with multifocal disease. The patients were 2 men and 1 woman aged 47-58 years (mean, 54 years). Two patients had evidence of autoimmune disease and their pulmonary disease was an incidental finding; one patient presented with non-specific respiratory symptoms. Radiologic imaging revealed multiple pulmonary nodules in all patients. Histologically, the tumors were solid-cystic and composed of cytologically bland, medium-sized ovoid to spindle cells with eosinophilic to clear cytoplasm arranged in a subtle nested pattern. These tumor cells were set in a highly vascularized stroma. Occasional cytologic atypia with multinucleated tumor cells was noted but mitotic activity was low. An infiltrate of mixed inflammatory cells was apparent in all tumors. Immunohistochemical analysis demonstrated diffuse expression of vimentin and TFE3 in all cases. Next generation sequencing revealed the presence of YAP1::TFE3 fusion in 1/1 case. All patients have remained alive albeit with stable or progressive disease, 24-66 months after diagnosis. These cases highlight the existence of multifocal pulmonary CCST and seem to support the notion that multifocality in CCST may be associated with more protracted clinical course. Awareness of the existence of multifocal pattern is important for patient management and prognosis.

Comprehensive pathological evaluation of risk factors for metastasis after endoscopic resection of superficial esophageal squamous cell carcinoma.

Esophageal cancer is a major cause of cancer mortality worldwide. Endoscopic resection (ER) is a curative treatment for esophageal squamous cell carcinoma (ESCC). Predicting risk of metastasis is crucial for post-ER management. In this study, we aimed to identify predictors of metastasis by examining endoscopically resected specimens. The cohort of this retrospective multicenter study comprised 422 patients who had undergone ER for ESCC from 1994 to 2017. Inclusion required a histological diagnosis of pT1a-muscularis mucosa or pT1b-submucosa (SM) cancer. Central pathological review comprehensively evaluated depth of invasion, lymphovascular invasion (LVI), droplet infiltration (DI), infiltrative growth pattern, histological differentiation, intraductal and intraglandular involvement, solitary nest, resected margin, and other factors. Logistic regression was used to identify predictors of metastasis. Metastases were identified in 103 patients. Univariate analysis identified LVI, depth of invasion, and DI as significant predictive factors. Multivariate analysis identified LVI, depth of invasion pT1b-SM2 (odds ratio 2.72) and indeterminate (positive vertical margin) (odds ratio 3.63) compared with the reference category of pT1b-SM1 as independent predictors of metastasis. Conversely, there were no significant associations between metastasis and lesion size, differentiation, cytological atypia, or infiltration pattern. Subgroup analysis showed that both the number and layer of LVI were associated with metastasis risk. In addition, four or more foci of DI was an independent predictor of LVI. LVI and depth of invasion were significant predictors of metastasis in ESCC. Detailed pathological evaluation and standardized criteria are essential for accurately assessing risk of metastasis and guiding post-ER treatment strategies.

Pigmented Syringomatous Carcinoma/Sweat Gland Carcinoma of the Vulva With Melanocytic Colonization: An Uncommon Presentation of a Rare Sweat Gland Neoplasm

Abstract: Primary vulvar carcinomas are rare and constitute a diverse group of neoplasms. These primary tumors are typically classified based on their presumed tissue of origin or histological characteristics. Among these, carcinomas of sweat gland origin are particularly significant. They closely resemble similar malignancies in nonvulvar skin, including various cutaneous adnexal-type cancers such as apocrine and eccrine adenocarcinomas. Syringomatous carcinoma of the vulva is a rare malignant sweat gland neoplasm known for its infiltrative growth and tendency for local recurrence. Typically, these malignancies manifest as nonulcerated nodules or plaques, primarily in the head and neck region. The occurrence of syringomatous carcinoma in the vulvar region is exceptionally rare. Herein, we present a unique case of a 35-year-old woman with a dark mole measuring 1.5 × 1.0 cm on the vulva. Complete excision was performed to exhibit an infiltrative haphazard proliferation of elongated ductules and tubules, displaying significant cytologic atypia characterized by irregular nuclear contours and variably prominent nucleoli. Extensive melanocytic pigment deposition and stromal fibrosis were also observed. Immunohistochemical staining demonstrated positive expression of epithelial markers, including keratins (AE1/AE3) and epithelial membrane antigen, supporting the diagnosis of syringomatous carcinoma. CK7 and carcinoembryonic antigen were negative, whereas SOX10 and pan melanin highlighted admixed, cytologically bland melanocytes within the epidermis and neoplastic nests. This case represents a highly unusual presentation of syringomatous carcinoma associated with melanocyte colonization. Due to limited data on the optimal management strategies, a multidisciplinary approach involving gynecologic oncologists, dermatopathologists, and radiation oncologists is essential for treatment decisions. Long-term follow-up is crucial, considering the potential for local recurrence and metastatic spread, emphasizing the importance of comprehensive clinical management for favorable patient outcomes of this rare malignancy.

CIC‐DUX4 Sarcoma of the Skin: A Rare Case Report and Literature Review

ABSTRACTCIC::DUX4 fusion sarcoma represents a rare and aggressive subtype of undifferentiated small round blue cell tumors. We report on a 23‐year‐old African male who developed a rapidly enlarging inferolateral left buttock nodule with ulceration. After debulking excision of the lesion, histologic sections demonstrated sheets and lobules of atypical round blue cells with significant cytologic atypia. Prominent foci of atypical mitotic figures and tissue necrosis were present. Tumoral cells stained strongly and diffusely using MDM2, vimentin, WT1 and CD99 immunohistochemical (IHC) markers. Molecular testing was performed and highlighted CIC::DUX4 gene fusion positivity, making the diagnosis of a CIC::DUX4 sarcoma (CDS). Post‐surgical excision, the patient showed no disease on imaging and underwent five cycles of adjuvant chemotherapy with no recurrence observed at the eight‐month follow‐up. With fewer than 200 cases reported in the literature and somewhat nonspecific clinicopathologic characteristics, CIC::DUX4 sarcoma presents a diagnostic challenge. This case underlines the importance of molecular diagnostics in undifferentiated sarcomas and presents a rare primary cutaneous manifestation of CIC::DUX4 fusion sarcoma. Additionally, we provide a review of the literature to aid in recognition, diagnosis, and treatment of this rare entity.

Histopathological diagnosis of pulmonary sclerosing pneumocytoma in needle biopsy specimens

Objective: To investigate the diagnostic features of pulmonary sclerosing pneumocytoma (PSP) in needle biopsy specimens so as to improve the preoperative diagnostic accuracy and to prevent misdiagnoses. Methods: A total of 79 needle biopsy cases confirmed as PSP in surgical resection specimens were collected in the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China from January 2015 to January 2023. A retrospective analysis was conducted to investigate the clinical, pathological, and immunohistochemical characteristics of PSP. Results: Among the 79 cases, there were 8 males and 71 females, with an age range of 14 to 67 years (median 47 years). Among the 79 needle biopsy cases of PSP, 5 cases were initially misdiagnosed as adenocarcinoma and 1 as carcinoid preoperatively, while the remaining 73 cases were correctly diagnosed. 84.8% (67/79) of the PSP presented with well-defined, homogeneous, solitary solid tumors on chest imaging. Morphologically, 26.6% (21/79) of the PSP mainly showed a single histological component, 67.1% (53/79) contained two histological components, and 6.3% (5/79) contained three histological components. There were no cases containing all four histological components simultaneously. The tumor was composed of cuboidal cells on the surface and round cells in the stroma and lacked significant cytological atypia and mitotic figures. Some cases exhibited variations in histology and cellular morphology, such as glandular spaces (58.2%, 46/79), sclerotic papillae (46.8%, 37/79), hypercellularity (16.5%, 13/79), and cytological atypia (24.1%, 19/79). Immunophenotyping indicated that both tumor cell types expressed TTF1, EMA and β-catenin, while surface cells expressed pan-cytokeratin and Napsin A, and stromal cells expressed vimentin. In some cases, ER and PR were also expressed. Conclusions: When diagnosing PSP in needle biopsy specimens, the key to avoiding misdiagnosis is recognizing the presence of dual-cell populations within the tumor. The useful clues include presence of cellular papillae, mild cellular atypia, morphological diversity, interstitial foam-like cell aggregates, and prominent background hemorrhage and sclerosis. The characteristic immunophenotype and middle-aged female predilection are also helpful for the diagnosis of PSP.

Histopathologic Comparisons of Discoid Lupus Erythematosus and Folliculotropic Mycosis Fungoides in a Series of 43 Cases.

Folliculotropic mycosis fungoides (FMF) is a rare cutaneous malignancy that can be mistaken for inflammatory diseases, such as discoid lupus erythematosus (DLE), due to the variability of histopathological findings. This study aims to provide dermatopathologists with evidence-based histopathologic criteria to distinguish DLE from FMF by reporting overlapping and distinguishing microscopic features. Forty-three biopsies from patients with a confirmed diagnosis of DLE or FMF were graded for the presence or absence of 18 histopathologic features. The main histopathologic findings present in nearly all DLE and FMF biopsies were folliculocentric and folliculotropic patterns. Comedones, granulomas, and folliculitis were not prominent. Follicular hyperplasia, follicular plugging, interstitial mucin, lichenoid/interface dermatitis, and plasma cells were significantly more common in DLE biopsies, while follicular mucinosis and eosinophils were significantly more common in FMF samples. Cytologic atypia ranged from none to mild in DLE and mild to moderate in FMF. Rarely, both sets of biopsies contained epidermotropism, spongiosis, or peri-eccrine infiltration. While many histopathological features present in DLE overlap with features found in FMF, such as folliculocentrism and folliculotropism, significant differences do exist. Therefore, when diagnosing FMF, it is important to follow established criteria that differentiate this malignancy from inflammatory conditions such as DLE.

Assessment of P16 and Ki-67 Proteins Immunoexpressing in Oral Mucosa Among Saudi Smokers.

It is widely known that tobacco use significantly contributes to a variety of health problems, including mouth cancer. The proteins P16 and Ki-67 have a role in regulating the cell cycle and promoting cell growth. Analyzing the levels of these proteins can give us valuable information about the overall health of cells. This study aims to assess the cellular alterations and immunohistochemical expression of P16 and Ki-67 in the oral mucosa of Saudi smokers. From March to December 2023, a cross-sectional study scraped 500 samples from the buccal mucosa. Participants in the study were Saudi citizens of both genders. We selected a total of 300 individuals who smoked cigarettes and 200 individuals who did not smoke tobacco as the control group. The selection process involved two sample techniques: initially purposive sampling and subsequently snowball sampling. The samples underwent an immunohistochemical examination to determine the presence of P16 and Ki-67 protein overexpression. We evaluated the samples by assessing the proportion of cells that exhibited positive staining and the intensity of the staining. The data were examined utilizing SPSS. We identified categorical variables by calculating frequencies and percentages using the chi-squared test. A significance level of p < 0.05 was used to determine statistical significance. A total of 48% of cigarette users had abnormal results, compared to 20% of nonsmokers. These abnormalities included cytological atypia, inflammation, reverse cytological infection, and binucleated or multinucleated cells (p = 0.015). People who smoked had higher levels of P16 and Ki-67 expressions than people who did not smoke, 12% and 5%, respectively (p = 0.042). There were no important changes in P16/Ki-67 expression between participants of different ages (p = 0.68) or between men and women (p = 0.27). These results demonstrate the detrimental effects of smoking on cell health, underscoring the importance of quitting to reduce the risk of cytological abnormalities and related diseases. Smokers have higher levels of the proteins P16 and Ki-67, which shows how important these biomarkers are for understanding the risks to oral health.

A woman with mycosis fungoides, vitiligo, and a new hand nodule.

A 70-year-old African American female with a history of stage IV mycosis fungoides in remission presented with a gradually enlarging, red, ulcerated nodule on her right dorsal hand. The lesion was biopsied, and it showed intraepidermal proliferation with cytologic atypia and increased vasculature in the papillary dermis. Immunohistochemical staining indicated a yes-associated protein 1 (YAP1) rearrangement, confirmed by RNA sequencing, revealing a YAP1::MAML2 (mastermind-like transcriptional coactivator 2) fusion. The lesion was diagnosed as an eccrine porocarcinoma (EPC). The occurrence of EPCs following radiotherapy or trauma has been documented. This case highlights the importance of considering EPCs in patients with extensive skin treatments and immunosuppression history.

Osteoblastoma Recurring as High-grade Osteosarcoma

Abstract Introduction/Objective Osteoblastoma is a benign, bone-forming neoplasm that presents as a well-circumscribed lesion amenable to excision. The prognosis is good despite a 20% recurrence risk. Malignant transformation is very rare. Osteoblastoma-like osteosarcoma is a rare form of osteosarcoma that shares similar clinical, radiographic, and pathological characteristics Methods/Case Report A 24-year-old female presented with a large palpable mass in the posterior occiput. The lesion progressively enlarged over 2 years, finally becoming symptomatic. Magnetic resonance imaging demonstrated an extradural posterior fossa expansile skull mass measuring 6.0 x 5.7 x 4.7 cm that showed multiple fluid/fluid levels. The mass was resected. Pathology demonstrated a well-circumscribed neoplasm that was cellular and composed of large polyhedral osteoblasts with eccentric oval nuclei and abundant amphophilic cytoplasm. Tumor cells were intimately associated with numerous small interconnecting, irregular bony trabeculae. Scattered mitotic figures of normal configuration were noted. The findings were compatible with an epithelioid osteoblastoma with prominent secondary aneurysmal bone cyst-like changes. The patient was lost to follow-up but presented 3 years later with severe migraines. Imaging demonstrated a large heterogeneous enhancing mass centered about the occipital cranioplasty with both intracranial and extracranial components. Reexcision was performed. Sections showed a well- circumscribed tumor, delineated by a rim of subperiosteal reactive bone, with an epithelioid morphology. However, it also demonstrated areas of necrosis, extensive sheet-like growth, conspicuous mitoses, and cytological atypia not seen in the previous specimen. Therefore, diagnosis of osteoblastoma-like osteosarcoma was rendered after expert consultation. Results (if a Case Study enter NA) NA Conclusion This case highlights the exceedingly rare evolving nature of osteoblastomas and their high-grade transformation potential.

The diagnostic challenge of a Papillary lesion of the breast in a patient with Peutz-Jeghers syndrome

Abstract Introduction/Objective Peutz-Jeghers syndrome (PJS) is an autosomal dominant disorder with elevated risk of various neoplasms, including breast cancer. The incidence of cancer among PJS patients is estimated to be 15-fold higher than the general population. The spectrum of breast lesions in PJS varies from benign papillomas to invasive carcinomas, presenting significant diagnostic complexities. The case presented here revolves around a unique papillary lesion in a PJS patient. Methods/Case Report A 40-year-old African American female, with PJS presented with a palpable abnormality in the right subareolar region with sanguineous nipple discharge. Multiple prior biopsies revealed intraductal papillomas with no atypia. Imaging showed a 7.0 cm complex solid and cystic subareolar mass, which had increased in size by 42% within a short period. Given the rapid increase in size, malignant transformation was clinically suspected. The patient underwent bilateral mastectomy. Macroscopic examination showed a 9.0 cm tan firm subareolar nodule with solid and cystic components. Histopathology revealed areas consistent with intraductal papilloma, however, additional complexities, including epithelial and myoepithelial proliferations with mild cytologic atypia, squamous, apocrine, and sebaceous metaplasia made the diagnosis challenging. No necrosis or increased mitotic activity was identified. Immunostaining for CK5/6 and p63 highlighted the myoepithelial layer, while estrogen receptor demonstrated heterogeneous positive staining. This picture raised suspicion of adenomyoepithelioma, but there was a significant overlap with intraductal papilloma. A final diagnosis of intraductal papillary neoplasm with epithelial and focal myoepithelial atypia was rendered. Results (if a Case Study enter NA) NA Conclusion This case presented a complex diagnostic dilemma. The rapid growth of the lesion, coupled with cytological atypia, raised significant concern necessitating precise differentiation between adenomyoepithelioma and intraductal papilloma. Further research is imperative to explore the pathophysiology of breast lesions in PJS, their impact on surveillance, management, potential for malignancy, and prognosis. Investigating additional diagnostic modalities and molecular markers to aid in accurate differentiation between benign and malignant papillary neoplasms in PJS patients warrants consideration.

Retroperitoneal Myoepithelial Carcinoma with Heterologous Bone Formation and EWSR1::ZNF444

Abstract Introduction/Objective Soft tissue myoepithelial tumors are rare tumors that affect a wide age range and diverse tissue sites. Fewer than five cases have been reported in the retroperitoneum. Most tumors are benign with the only histologic criterion for malignancy being cytologic atypia. The morphology is broad ranging from spindled to epithelioid cells of varying cellularity in sclerotic to myxoid stroma. Heterologous differentiation may be present. These tumors usually express cytokeratin, EMA, S100, and GFAP and show EWSR1 and FUS rearrangements. Here we present an unusual case of retroperitoneal myoepithelial carcinoma. Methods/Case Report A 29-year-old female presented with rash and painless jaundice. CT and MRCP revealed a relatively circumscribed 3.7 cm mass in the porta hepatis. On fine needle aspiration, a possible gastrointestinal stromal tumor was considered due to DOG1 expression. The patient underwent a Whipple procedure with negative margins showing tumor in soft tissue adjacent to the common bile duct. The tumor was multinodular and consisted predominantly of mild to moderately pleomorphic epithelioid cells in fibromyxoid stroma with interspersed woven bone. Mitoses were not appreciated, and necrosis not seen. The tumor was focally positive for CK AE1/AE3, GFAP, and DOG1 and negative for S100, SOX10, p63, and CD117. INI1 was retained. NGS identified EWSR1::ZNF44 and a diagnosis of myoepithelial carcinoma was rendered. The patient received no adjuvant therapy and has not shown any evidence of metastasis or recurrence for 17 months. Results (if a Case Study enter NA) NA Conclusion Soft tissue myoepithelial carcinomas are aggressive tumors with approximately 40% recurrence and over 50% metastasis. Standard treatment is complete surgical resection. The efficacy of radiation and chemotherapy is not clear. EWSR1 fusions with various partners including POU5F1, PBX1/3, and ZNF44 have been identified. Due to their rarity and varying histology and immunohistochemical expression, identification of gene fusions can be invaluable in diagnosing soft tissue myoepithelial tumors, especially in unusual locations.

Clonal Bronchopulmonary B-Cell Proliferations of Indeterminate Malignant Potential in Patients with Common Variable Immune Deficiency (CVID) associated Granulomatous Lymphocytic Interstitial Lung Disease (GLILD)

Abstract Introduction/Objective Pulmonary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) is often challenging to distinguish from reactive nodular lymphoid hyperplasia, and assessing B-cell clonality in such cases is crucial in making the distinction. However, patients with common variable immune deficiency (CVID) can harbor clonal or oligoclonal lymphoid populations in their tissues, particularly in association with granulomatous lymphocytic interstitial lung disease (GLILD), making the distinction from MALT lymphoma extremely challenging. We report six cases of GLILD with clonal or oligoclonal B cell infiltrates in lung wedge resection specimens and describe their clinicopathologic characteristics, management, and outcomes. Methods/Case Report A retrospective review was performed to collect lung wedge resection specimens from patients with CVID showing atypical B-cell infiltrates associated with GLILD between 01/2015 and 08/2023. The clinicopathologic findings, management, and response to treatment were studied. Results (if a Case Study enter NA) A total of six GLILD cases were identified with variable degrees of architectural and cytologic lymphoid atypia. Clonality of the lymphoid infiltrate was assessed by kappa/lambda in situ hybridization staining in all six, flow cytometry in 3/6, and IGH gene rearrangement in 4/6 cases. The infiltrate showed frank lambda restriction in 1/6, lambda predominance in 1/6, polytypic expression in 1/6, and no significant plasmacytic component in 3/6 cases. Flow cytometry detected atypical light chain skewed B-cell populations in 3/3 of cases. IGH was positive for clonality in 3/4 and oligoclonal in 1/4 cases. Four patients received therapeutic intervention for GLILD, including one with Rituximab monotherapy, two with Rituximab+Azathioprine, and one with Rituximab+Mycophenolate leading to marked symptomatic and radiologic improvement in all four patients. The remaining two patients were observed to have stable disease. Conclusion Patients with CVID can harbor clonal B-cell populations due to their underlying immune dysfunction. Studies have shown that these can be transient and may not always progress to overt lymphoma. In the setting of GLILD, detecting these populations makes the distinction from MALT lymphoma very challenging. Given that the first- line therapy for both GLILD and MALT is anti-CD20 therapy, the malignant potential of these clones remains uncertain and can only be determined with long-term clinical follow-up.

Superficial angiomyxoma-like myxofibrosarcoma

Abstract Introduction/Objective Myxofibrosarcoma comprises a spectrum of malignant fibroblastic neoplasms with variably myxoid stroma, pleomorphism, and a distinctive curvilinear vascular pattern. Herein we describe a case of myxofibrosarcoma with unusual histological features that could be deceptive, mimic superficial angiomyxoma and make the diagnosis challenging Methods/Case Report A 74-year-old female presented with a right upper arm lesion that had been present for 10-12 months and had significantly increased in size over this time and became painful. There was no history of trauma. Examination demonstrated approximately 3 cm multinodular mass along the anterior aspect of the proximal arm. There were no overlying skin discolorations or ecchymosis. The patient underwent a shave biopsy and then resection. Grossly, the lesion was gray-white firm with an ill-defined border covered with a tan-white skin ellipse. Histologically, the lesion was located in the dermis extending to the dermal-epidermal junction. The lesion comprised mainly of myxoid stroma, arborizing, and plexiform thin-walled blood vessels, stellate to spindled cells with enlarged hyperchromatic nuclei, and eosinophilic cytoplasm in addition to the presence of stromal neutrophils and hyperplastic overlying squamous epithelium. The morphologic appearance elicited the differential diagnosis of superficial angiomyxoma and low-grade myxofibrosarcoma. While many features were more suggestive of superficial angiomyxoma, the degree of atypia and mitotic activity (12/10 HPF) was outside the realm of angiomyxoma and warranted the diagnosis of myxofibrosarcoma Results (if a Case Study enter NA) NA Conclusion Although rare, myxofibrosarcoma may rarely extend to the dermal-epidermal junction and mimic superficial angiomyxoma. The presence of cytologic atypia and increased mitotic activity favors myxofibrosarcoma

Leiomyoma with bizarre nuclei occurring post hysterectomy mimicking malignancy: a rare case report

Abstract Introduction/Objective Leiomyoma with bizarre nuclei (LBN), also known as symplastic leiomyoma, represents a rare subtype of benign uterine smooth muscle neoplasm. Histologically, it is characterized by significant cytological atypia in a typical leiomyoma background with rare mitoses and without tumor necrosis. Methods/Case Report We report a case of a 48-year-old woman, status post hysterectomy for symptomatic fibroids, with imaging showing multiple contiguous pelvic masses extending from the pelvis to the upper abdomen and displacing the colon laterally and small bowel posteriorly. The findings were highly suspicious for ovarian malignancy. A bilateral salpingo-oophorectomy and a partial colectomy were performed with tumor debulking and omentectomy. Grossly, multiple well-circumscribed soft masses ranging in size from 1.5-16 cm, in contiguity with pericolonic mesentery with a smooth fleshy cut surface and cystic changes were found. Bilateral ovaries were unremarkable. Microscopically the larger masses were composed of spindle cells with bizarre nuclei throughout, while smaller masses showed foci of bizarrely shaped-spindle cells with bizarre nuclei in a background of a typical leiomyoma. Mono- and multinucleated cells with smudged chromatin were also seen. The mitotic index was low confirmed with a low Ki-67 proliferation index (&amp;lt; 5%). Immunohistochemical stainings showed that the neoplastic cells were positive for desmin, SMA, and caldesmon; and negative for CD10, with a wild type p53 expression. Fumarate hydratase immunostain was retained. MDM2 amplification was not detected by FISH. The morphology and immunohistochemical findings were compatible with LBN. Results (if a Case Study enter NA) NA Conclusion In summary, this is a rare and challenging case of multiple LBN developed years post hysterectomy and clinically mimicking a malignancy.

ALK-Positive Histiocytosis and its Distinctive Manifestation in the Breast

Abstract Introduction/Objective ALK-positive histiocytosis (APH) is a rare histiocytic proliferation disease that harbors ALK rearrangements, often involving fusion with KIF5B. Primary cases in the unilateral breast are exceptionally uncommon, with only a few reported cases globally, characterizing it as a unique histiocytic proliferation disorder. Methods/Case Report In our study, we report a case of unilateral multifocal breast involvement of ALK-positive histiocytosis following bilateral breast core biopsies in a 56-year-old Hispanic woman who presented with bilateral breast masses. Right breast imaging demonstrated multiple nodular densities, further characterized on ultrasound as a hypoechoic region of 8 cm with increased vascularity. On right breast biopsy, prominent proliferation of histiocytes (lacking high-grade cytologic atypia) with chronic inflammation, few giant cells, and focal cholesterol clefts were identified. On immunohistochemical studies, the lesional cells were variably positive for histiocytic markers CD68, CD163, and PU.1 and were negative for S100 and pancytokeratin. ALK1 showed multifocal staining in the lesional cells as confirmed on repeat study; however, ALK (D5F3), GMS and acid fast studies were negative. The presence of focal cholesterol clefts, scattered giant cells, and chronic inflammation lead us to consider aberrant ALK expression in a reactive process. However, APH was definitively diagnosed through confirmation of clonal histiocyte proliferation, observed findings on morphology, immunophenotyping, and the presence of KIF5B-ALK gene fusion as detected by comprehensive solid tumor fusion panel testing. Results (if a Case Study enter NA) NA Conclusion It is noteworthy that ALK-positive histiocytosis can occasionally present alongside features of a reactive process in the breast. Therefore, considering any history of prior surgery or trauma at the lesion site is crucial. However, we recommend a comprehensive approach in most cases, which includes morphological, immunohistochemical, and molecular analysis on all suspected histiocytosis cases. This approach aims to increase awareness and detection of this rarely described entity and to precisely distinguish it from other diseases for prognostic and therapeutic purposes.

Giant pilomatricoma with atypical features: report of a case of aggressive pilomatricoma in an adult

Abstract Introduction/Objective Pilomatricoma, also known as pilomatrixoma or calcifying epithelioma of Malherbe, is a relatively common, benign tumor of the hair matrix. It typically presents as a small (~1cm), dermal based mass in the head and neck region of children and young adults (under 20 years) with predominance for males, but can occur in any age. In contrast, malignant pilomatricoma is typically larger (1 to 10 cm) and occurs later in life (50-60 years). Aggressive pilomatricoma is a variant of pilomatricoma that tends to occur in children and demonstrates atypical features such as increased matrical cells and nuclear atypia, but insufficient for a classification as pilomatrical carcinoma. Here, we presented a case of a large (14.5 cm) aggressive/atypical pilomatricoma that occurred in an adult. Methods/Case Report A 45 year-old-female presented to the emergency department with a posterior neck mass which has been slowly enlarging for years. Recently, it became painful with sanguineous discharge which prompted her to seek medical attention. CT scan revealed a lobulated, pedunculated mass with fat and fluid components. An excision was performed. Gross examination revealed an ulcerated mass measured 14.5 cm in greatest dimension. Scattered calcifications were present. Microscopically, nests of basaloid cells with scattered shadow cells are present consistent with matrical differentiation. A multinodular growth pattern with central necrosis was evident. Nuclear atypia characterized by prominent nucleoli and nuclear overlapping was identified. Results (if a Case Study enter NA) NA Conclusion Histopathologic criteria to reliably differentiate between benign and malignant pilomatrical tumors are not well-established. Tumor ulceration, asymmetry, irregular borders, multinodular growth pattern, marked cytologic atypia, prominent necrosis, lymphovascular invasion, and perineural invasion may be used in favor of malignancy. Our case showed focal confluent necrosis, ulceration, multinodular growth pattern, and cellular atypia but lacked other features that indicative of unequivocal malignancy. The resection margins were negative for tumor. Clinical followup was negative for signs of recurrence or metastasis after two years. We presented this case to show the large size that aggressive pilomatricoma can reach and to emphasize the difficulty in differentiating benign from malignant pilomatrical tumors in borderline cases.

Immunohistochemical Glutamine Synthetase As a Surrogate Marker for Beta Catenin (Exon 3 Deletion) in a Rare Case of Hepatic Adenomatosis with Early Malignant Transformation to Well Differentiated Hepatocellular Carcinoma

Abstract Introduction/Objective Hepatic adenomatosis (HA) is a rare entity defined by ≥ 10 hepatocellular adenomas (HCAs). About half of HA cases are asymptomatic and incidentally found. Compared to individual HCAs, HA carries a higher risk of complications including: tumor rupture, bleeding, and an approximate 4.2% overall frequency of malignant transformation. Methods/Case Report A 29-year-old woman presented to the emergency department (ED) requesting a CT scan. She was seen by a gastroenterologist days prior to her ED visit for ongoing sharp rectal pain for 2-3 months. After a recent rectal exam, she was recommended to have a CT abdomen/pelvis to rule out a potential abscess. CT did not show a perianal or perirectal abscess but instead identified a 9.1 cm right hepatic lobe mass. A liver MRI showed a 6.4 x 8.5 cm mass with arterial enhancement. The patient had a prior history of OCP use. She underwent robotic wedge resection of liver segment 6 with cholecystectomy. Gross examination showed a 6 cm tumor with many smaller nodules ranging in size from 0.5-2.2 cm. Our case was submitted entirely for histologic examination. Microscopy demonstrated well differentiated hepatocellular carcinoma (WDHCC) confirmed with positive immunohistochemical (IHC) staining for HepPar1 and Arginase. Tumor cells showed mild patchy cytological atypia, occasional pseudoglands, and architectural atypia with “nodule in nodule growth.” There was reticulin loss in multiple areas and CD34 showed strong diffuse sinusoidal staining. Glypican 3, CRP, and HAA were negative. Low Ki-67, LFABP retention, and absent nuclear staining of beta catenin (BC) were noted. Glutamine synthetase (GS) was diffuse and homogeneous. The gallbladder was unremarkable. Results (if a Case Study enter NA) NA Conclusion This case emphasizes that, despite negative nuclear BC staining, diffuse homogenous staining of GS is a quality surrogate marker for BC mutations (ex. exon 3 deletions). Thorough gross, microscopic, and molecular examination in HA cases is essential for identifying transformation to WDHCC.

Benign Cystic Mesothelioma of the Uterus: Myth or Reality?

Mesothelioma is a very rare tumor of mesodermal origin that covers the surface of body organs such as the peritoneum, pleura and pericardium. This tumour in the majority of cases presents in its malignant form where it represents some characteristics: increased cellularity, cytological atypia, papillary formations, even invasion. We report the case of Mrs AB, 37 years old, blood group A positive with no particular pathological history, nulli gesture nulli pare, consulted for pelvic pain and abdominal bloating. The clinical examination showed a distended bloated abdomen with a 20 centimetre pelvic mass with regular contours and painlessness. Abdominal and pelvic ultrasound showed a globular uterus increased in size by 200 millimetres with a multilocular cystic image intra myometrial (corporal anterior and fundial) of 188*79 millimetres. Intraoperatively, a globular uterus was found to be enlarged with a 15 centimetre parovascular cystic mass, dependent on the anterior aspect of the uterus, with a rock water fluid content, without any other associated abnormalities The postoperative course was simple. To conclude, Benign cystic mesothelioma of the uterus is a tumour of diagnostic value. This tumour is spleen. The preoperative evaluation allows the diagnosis to be suspected, especially by pelvic magnetic resonance imaging.

HMGA2-positive salivary gland neoplasms with prominent trabecular/canalicular morphology: a focus on carcinomas arising within this phenotype.

Pleomorphic adenoma (PA) with a prominent trabecular/canalicular morphology has consistent HMGA2 protein expression, and association with HMGA2 fusions. We report our experience with this subtype, with emphasis on the carcinomas that can arise in this context. A retro- and prospective review (2013-2024) of major salivary gland tumours with prominent trabecular/canalicular morphology was performed. Twenty-one parotid tumours met the criteria: 14 benign (66.7%), six carcinomas (28.6%), and one of uncertain behaviour (4.7%). HMGA2 immunohistochemistry (IHC) was performed on all cases. Next-generation sequencing was successfully performed on 18. Seven benign cases had a conventional PA component. In all cases, the tumour cells in these trabecular/canalicular areas demonstrated variable papillary thyroid carcinoma-like nuclear changes, including chromatin clearing, overcrowding, membrane irregularities, and intranuclear pseudoinclusions. Benign tumours were well-demarcated, whereas carcinomas demonstrated either a multinodular pattern of invasion or subtle infiltration. Two carcinomas showed increased cytologic atypia and architectural complexity and one had perineural invasion. By IHC, all were positive for HMGA2. In the trabecular/canalicular areas, there was consistent strong expression of CAM5.2, S-100, and SOX-10 and variable expression of p63 but negative p40. HMGA2 alterations were detected in 16 of 18 cases (89%). Follow-up was available on two carcinomas, with one being locally recurrent. While most HMGA2-positive salivary gland neoplasms with a prominent trabecular/canalicular growth pattern are benign, they, like traditional PAs, may give rise to carcinomas that can locally recur. These carcinomas can be deceptively bland, subtly infiltrative, or have a multinodular pattern of invasion.