International Journal of Surgical Pathology

The prognostic role of tumor cells in pancreatic ductal adenocarcinoma (PDAC) of the pancreatic head with direct microscopic infiltration (DMI) or in close proximity (≤1 mm) to the resection margin (RM) remains unclear. This single-center, retrospective study included specimens from 75 patients who underwent oncological resection of pancreatic head PDAC between February 2013 and July 2020. Two pathologists independently re-measured the distance between tumors and the multiple RMs. The impact of RM involvement for DMI, tumor cells within ≤1 mm, in general, and for individual RMs on overall survival (OS) and development of distant pulmonary (PM) and hepatic (HM) metastasis was analyzed. DMI of RMs was significantly associated with a shorter OS (median 5 vs 19 months, P = .02). The presence of tumor cells within ≤1 mm of RMs yielded a negative impact on OS with a trend toward significance (median 9 vs 21 months, P = .09). DMI and tumor cells within ≤1 mm of the pancreatic transection margin (PRM), individually, had a significant negative impact on OS (median 4 vs 19 months and 6 vs 19 months, P < .05), but not for any other individual RM. RM involvement of ≤1 mm of only the vascular circumferential resection margin (VCRM) resulted in a shorter time to HM development (P = 0.05). DMI of the posterior circumferential resection margin (PCRM) and VCRM, individually, showed shorter time to PM (P < .05). Potential clinical considerations include extended intraoperative evaluation of the PRM (1 mm) and intensified preoperative prediction of R1 resection as a basis for neoadjuvant therapy.

Introduction. The identification of mitotic figures is essential for the diagnosis, grading, and classification of various different tumors. Despite its importance, there is a paucity of literature reporting the consistency in interpreting mitotic figures among pathologists. This study leverages publicly accessible datasets and social media to recruit an international group of pathologists to score an image database of more than 1000 mitotic figures collectively. Materials and Methods. Pathologists were instructed to randomly select a digital slide from The Cancer Genome Atlas (TCGA) datasets and annotate 10-20 mitotic figures within a 2 mm² area. The first 1010 submitted mitotic figures were used to create an image dataset, with each figure transformed into an individual tile at 40x magnification. The dataset was redistributed to all pathologists to review and determine whether each tile constituted a mitotic figure. Results. Overall pathologists had a median agreement rate of 80.2% (range 42.0%-95.7%). Individual mitotic figure tiles had a median agreement rate of 87.1% and a fair inter-rater agreement across all tiles (kappa = 0.284). Mitotic figures in prometaphase had lower percentage agreement rates compared to other phases of mitosis. Conclusion. This dataset stands as the largest international consensus study for mitotic figures to date and can be utilized as a training set for future studies. The agreement range reflects a spectrum of criteria that pathologists use to decide what constitutes a mitotic figure, which may have potential implications in tumor diagnostics and clinical management.

Introduction. Tumors and tumor-like lesions of the uterine adnexa in children and adolescents are uncommon but may carry devastating consequences. Methods. We conducted an observational retrospective cohort study, to describe patients aged 0 to 19 years diagnosed with tumors and tumor-like lesions of the uterine adnexa at our institution between 2000 and 2018. Results. Eighty-nine patients with 105 adnexal lesions were included. Thirty-seven (42%) patients presented with benign tumors, 13 (15%) with borderline tumors, 25 (28%) with malignant tumors and 14 (16%) with tumor-like lesions. Germ cell tumors (n = 45|43%) were the most frequent, followed by epithelial tumors (n = 30|29%). No significant differences were found in the age distribution of the lesions by malignant potential or histologic group. Most patients (n = 80|90%) were treated primarily with conservative surgery, including cystectomy (n = 25|28%) and unilateral oophorectomy/adnexectomy (n = 54|61%). Thirty-four (38%) underwent surgical staging (partial omentectomy and peritoneal biopsies). Twenty (23%) patients with borderline and malignant tumors were submitted to chemotherapy. Four (5%) patients with borderline or malignant tumors relapsed, one of whom died from disease. Conclusion. Gynecological lesions in children and adolescents encompass a wide range of rare histological tumor subtypes, requiring evaluation by experienced pathologists. Most tumors were diagnosed at early stages, with low relapse and mortality rates. Conservative management, with fertility sparing surgery and limited use of adjuvant chemotherapy, is of utmost importance.

Comorbidities between tuberculosis and leprosy are expected in endemic regions. Pulmonary tuberculosis and cutaneous leprosy are the most prevalent coinfections. One of the common manifestations of tuberculosis is generalized lymphadenopathy. In contrast, leprosy is clinically less suspected to manifest as a generalized lymphadenopathy, and it is pathologically unusual to diagnose leprosy primarily in lymph nodes. Concomitant tuberculous and lepromatous lymphadenitis are unprecedented and clinically unexpected, particularly in nonendemic countries. This imposes diagnostic challenges. We report concurrent tuberculosis and leprosy that were diagnosed in a lymph node in 45-year-old man with generalized lymphadenopathy. The effaced lymph node was predominantly replaced by caseating epithelioid granulomas alternating with foamy histiocytes. Ziehl-Neelsen stain showed positive acid-fast bacilli in the necrotizing granulomas only. The initial differential diagnosis of the nodal foamy macrophages included fungal infections, leishmaniasis, and Whipple disease, for which the special stains were negative. The vacuolated macrophages were disregarded as nonspecific lipogranuloma. A modified acid-fast stain was not considered. The histopathologic clues to nodal lepromatous leprosy included the presence of intracytoplasmic globi, intermixed microabscesses, and lymphoplasmacytic infiltrate and involved pericapsular nerves. Wade-Fite stain was subsequently performed. It revealed numerous lepra bacilli within the foamy histiocytes. The final diagnosis was concurrent disseminated tuberculosis and leprosy. Nodal lepromatous leprosy could be missed when compounded by concurrent nodal tuberculosis, particularly in developed countries. The clinicians and pathologists should have a high index of suspicion, particularly in patients from or with history of travel from endemic regions. Certain histopathologic features are helpful clues to avoid pitfalls.

Sometimes non-neoplastic changes of the gastric mucosa mimic diffuse-type gastric carcinoma, specifically signet-ring cell adenocarcinoma. In fact, gastric epithelial cells undergoing signet-ring cell change have a cellular morphology that is almost identical to signet-ring cell adenocarcinoma, often leading to misdiagnosis. Accurate recognition of signet-ring cell change is essential to avoid overdiagnosis and overtreatment of signet-ring cell adenocarcinoma. Research on this topic is limited and clinicians lack formal diagnostic tools when signet-ring cells are detected in biopsy specimens. The aims of this study are 3-fold. Firstly, to increase the awareness of both clinicians and pathologists of this rare but highly significant entity. Secondly, to report 4 additional examples of signet-ring cell change and analyze them alongside signet-ring cell adenocarcinoma to compare their morphological and phenotypic features and their evolution over time. Finally, to highlight the potential utility of endoscopic resection to confirm the diagnosis. Cells in signet-ring cell change strongly express E-cadherin, show a wild-type p53 expression, and have a low Ki67 index. In contrast, cells in signet-ring cell adenocarcinoma strongly express p53, have high proliferation rates, and show either no or weak E-cadherin staining. Genetic analysis may be useful in identifying patients at risk of hereditary early diffuse gastric adenocarcinoma, which can mimic signet-ring cell change.

Background. Fixed drug eruption and Rowell syndrome stand as intriguing entities with overlapping clinical and pathological features. Case Presentation. A 32-year-old female patient presented with a tender and pruritic rash on the left upper chest for 3 days. Clinical examination revealed a flaring rash on the chest, under her left eye, tongue, and lips. The patient had a significant past medical history of systemic lupus erythematous with positive (ANA, Sm, dsDNA, ribosomalP, RNP) antibodies, hypocomplementemia, inflammatory arthritis, discoid lupus, leukopenia, thrombocytopenia, and immune thrombocytopenic purpura, and avascular necrosis affecting both hips and her right knee. At the time of presentation, the patient was on azathioprine 150 mg daily and hydroxychloroquine 200 mg twice daily. Skin biopsy of the left upper chest revealed interface dermatitis with necrotic keratinocytes at the dermal-epidermal junction. Superficial and, in some areas, deep perivascular and peri adnexal lymphocytic infiltrates were observed, accompanied by eosinophils. CD123 staining highlighted 16% of the inflammatory cells. Direct Immunofluorescence for IgG, IgA, IgM, C3, and fibrinogen revealed positive linear basement membrane staining for IgG and fibrinogen, with no significant staining for the remaining immunoreactants. Considering the patient's history of medicine usage, and negative SS-A and SS-B antibody, a fixed drug eruption was favored. Discussion. This article discusses the clinical presentations, pathophysiological mechanisms, and diagnostic criteria for fixed drug eruption and Rowell syndrome. Conclusion. Awareness of the distinct clinical and histopathologic features of fixed drug eruption and Rowell syndrome, particularly when sharing cutaneous manifestations, underscores the importance of a comprehensive diagnostic approach and laboratory testing.

The diagnosis of low-grade fibroblastic/myofibroblastic tumors of acral sites can be challenging. These tumors encompass a diverse group of neoplasms with a spectrum of biologic potential ranges from benign to overtly malignant. They often demonstrate significant clinical, radiologic, and immunophenotypic overlap, in which the molecular phenotype may play an important diagnostic role to arrive at the final diagnosis. Herein, we report a case of soft tissue mass lesion presented on the palm of an adult patient for four months. Histologically, the tumor consisted of primarily low-grade spindle cells expressing smooth muscle actin. Molecular testing revealed a novel SREBF1::USP6 fusion gene, confirming the final diagnosis of nodular fasciitis and ultimately expanding its molecular profile. This case highlights the diagnostic value of single, cost-effective, targeted molecular panel to arrive at an accurate diagnosis and provide helpful therapeutic information.

The clinical, radiological, and histopathological features of chondromyxoid fibroma can sometimes resemble those of other benign or malignant tumors. Recently, recurrent GRM1 rearrangements have been identified in chondromyxoid fibroma, and GRM1 positivity by immunohistochemistry has emerged as a dependable surrogate marker for this molecular alteration. Phosphaturic mesenchymal tumor is a rare tumor that often exhibits overexpression of fibroblastic growth factor 23 (FGF23) through various mechanisms. In this report, we present a case of GRM1-rearranged chondromyxoid fibroma that also exhibited FGF23 expression via in situ hybridization, posing significant diagnostic challenges during workup of the initial core biopsy. We hope that this case can serve as an educational resource, shedding light on a rare diagnostic pitfall.

Succinate dehydrogenase (SDH)-deficient renal cell carcinoma (RCC) is a rare epithelial tumor with a biallelic mutation involving any subunit of the SDH complex. Mostly, it has low-grade morphology and a favorable prognosis. We present a case of a 36-year-old woman with weight loss, night sweats, and symptomatic anemia. Her imaging showed a hypo-enhancing heterogeneous right renal mass with invasion of the renal vein and inferior vena cava. Microscopically, the tumor had focal low-grade areas (5%) and extensive areas with high-grade features, including rhabdoid (85%) and sarcomatoid (10%) dedifferentiation. Cytoplasmic inclusions, foci of extracellular mucin, coagulative necrosis, and inflammatory infiltrate were present. The tumor cells, including rhabdoid differentiated, were focally positive for AE1/AE3. Tumor cells showed loss of SDHB immunostaining, consistent with diagnosis. Genetics testing was recommended, but the patient expired due to metastatic carcinoma. Prior studies suggest that sarcomatoid transformation and coagulative necrosis increase the risk of metastasis by up to 70% in SDH-deficient RCC. Follow-up with surveillance for other SDH-deficient neoplasms is recommended in cases of germline mutation. Here, we report the first case of SDH-deficient RCC with concomitant rhabdoid and sarcomatoid features and a detailed review of diagnostic difficulties associated with high-grade tumors.

Granular cell tumor, which is thought to recapitulate a Schwann cell phenotype, is a very rare neoplasm that belongs to soft tissue tumors. It can be classified as benign, atypical or malignant, based on specific histological criteria, with the majority of cases exhibiting an indolent behavior. Its biology and clinical course are poorly understood and its optimal management is yet to be defined, given the rarity of cases. Here we describe an atypical granular cell tumor in the upper middle back skin that evolved after a thirty-year indolent period. Despite complete surgical removal, the patient experienced a recurrence, both local and in the lungs, following an aggressive clinical course. Data on management of metastatic disease are extremely scarce, comprised exclusively of case reports. Therefore, we administered to the patient systemic therapy according to soft tissue sarcoma guidelines, which led to disease progression, with fatal outcome. In conclusion, recurrent and/or metastatic granular cell tumor is a rare disease that can be life-threatening, for which response to different therapies is unknown. The biologic behavior of atypical and malignant granular cell tumor is quite different from its benign counterpart, evoking soft tissue sarcomas, and its diagnosis should alert clinicians. The role of adjuvant chemotherapy and radiation therapy in this setting should be explored, to limit disease recurrence.

“Tumor-to-tumor metastasis,” an uncommon phenomenon, refers to a primary tumor metastasis into another tumor, with the most frequent donor being lung carcinoma and common recipients being renal cell carcinoma and meningioma. Tumor-to-tumor metastasis occurring in gliomas is rare with less than 20 reports described so far, and that into a glioblastoma is even rarer. We report a 54-year man, diagnosed with glioblastoma, IDH-wildtype, with metastasis of an adenocarcinoma into it. On histomorphology, the glial component was composed of astrocytic cells and showed increased mitosis, microvascular proliferation, and focal necrosis. This was intermingled with an adenocarcinomatous tumor with pleomorphic epithelial cells in glands, nests, and sheets. On immunohistochemistry, the adenocarcinomatous areas were positive for AE1/AE3 and TTF1 but negative for glial markers, ruling out adenoid glioblastoma. Further cytogenetic analysis showed EGFR amplification in the glial component but not in the adenocarcinoma component, ruling out glioblastoma with true epithelial metaplasia, and supporting the diagnosis of adenocarcinoma metastasis into glioblastoma. Glioblastomas may be susceptible to intratumoral metastasis due to the proliferating leaky vascular channels, however, the short survival of patients with glioblastoma may be responsible for the rarity of this occurrence. The documentation of these tumors is important as they may be important for clinical diagnosis and further treatment and prognosis.

The entity commonly referred to as chondrolipoma is a rare and enigmatic breast lesion with unclear histogenesis and a complete lack of molecular characterization. It is uncertain whether it represents a hamartoma, choristoma, or a distinct neoplasm, including possibly a variant of mammary-type myofibroblastoma. We report two additional chondrolipomatous lesions of the breast. The lesions had varying histologic and immunohistochemical features similar to myofibroblastoma, including the loss of retinoblastoma (Rb) protein expression in one lesion. Molecular analysis by chromosomal microarray analysis performed on a second lesion did not demonstrate a loss of 13q14 or 16q typical of myofibroblastoma. Our findings further support the concept that at least a subset of breast lesions that historically have been classified as chondrolipoma are related to myofibroblastoma. However, the lack of myofibroblastoma-specific molecular alterations in one lesion suggests chondrolipomas may also have varying origins.

Wnt signaling pathway activation is involved in the pathogenesis of a series of malignant tumors and is characterized by the nuclear accumulation of β-catenin protein. The occurrence of two or more Wnt pathway-associated tumors in a single individual is uncommon and generally attributed to inherited cancer syndrome, especially familial adenomatous polyposis (FAP). Herein, we presented a rare case of a child who suffered from the occurrence of Wnt-activated medulloblastoma and cribriform-morular thyroid carcinoma (CMTC) within a 9-year interval. She had no history of FAP and harbored an unexpected somatic mutation of the APC gene in the CMTC tumor. The potential agents involved in the pathogenesis of the two molecular-linked tumors other than FAP were discussed in this report.

Sarcomatoid yolk sac tumor is a very rare histologic type of testicular germ cell tumor and is mainly reported in testicular germ cell tumor patients who receive chemotherapy. Herein, we report an extremely rare concurrent retroperitoneal sarcomatoid yolk sac tumor in a man with a testicular postpuberal teratoma before he received chemotherapy. A 37-year-old man initially presented with a persistent abdominal pain. Subsequent imaging studies revealed a 9.6-cm retroperitoneal mass, and 2 testicular masses (3.1 cm and 0.9 cm in greatest dimension, respectively). His serum tumor markers were within normal ranges. His radical orchiectomy demonstrated a postpubertal type teratoma with an adjacent scarring nodule. Later, his retroperitoneal tumor showed spindle tumor cells embedded in predominantly myxoid and focally fibrous stroma with diffuse and strong immunoreactivity for keratin AE1/AE3, SALL4 and glypican 3. No tumor necrosis or brisk mitotic figures were observed. A diagnosis of sarcomatoid yolk sac tumor was rendered. Fluorescence in situ hybridization analysis of his retroperitoneal sarcomatoid yolk sac tumor revealed polysomy 12 and MYC amplification, whereas no evidence of isochromosome 12p [i(12p)], and DNA sequencing showed 6 mutations per megabase (muts/Mb), and the somatic alterations included ARAF amplification and ATR I774Yfs*5. Considering its rarity, sarcomatoid yolk sac tumor may pose diagnostic challenges. Therefore, relevant clinicoradiologic information and ancillary work up, including immunohistochemistry and molecular studies, may be helpful for the accurate classification. Our tumor further raises awareness of this rare event, expands the spectrum of its clinical presentation, and explores the molecular features.

Liesegang rings are eosinophilic, concentric, lamellated structures that can assume a variety of shapes and sizes ranging from a few microns to hundreds of microns. To date, Liesegang rings have been reported in around 30 examples in the English literature, in the kidney, breast, female genital tract, and skin, and only a single report in the lung associated with allergic bronchopulmonary aspergillosis. Liesegang rings are usually incidental discoveries and have been associated with benign cystic lesions, inflammatory diseases, fibrosis, and tissue necrosis. Their typical appearance helps differentiate them from their mimics including parasites, foreign materials, corpora amylacae, and psammoma bodies. We report Liesegang rings in a 62-year-old male patient with pulmonary tuberculosis to create awareness about this rare entity among pathologists to avoid its misdiagnosis as a parasitic infection.

Canalicular-like pleomorphic adenomas are a relatively recently described entity, that possess features of both canalicular adenomas and pleomorphic adenomas. The presence of unusual HMGA2-fusion partners (most commonly HMGA2::WIF1 gene fusions) has established canalicular-like pleomorphic adenoma as a distinct entity. The use of intraoperative frozen section analysis and surrogate HMGA2 IHC are 2 tools that can provide the surgical team with valuable insight into intraoperative decision making and final classification of rare tumors of the parotid gland, respectively. We present a case of canalicular-like pleomorphic adenoma and characterize its appearance on frozen section analysis. HMGA2 IHC staining was retroactively performed, assisting in the confirmation of the tumor subtype.

Metastasis of clear cell renal cell carcinoma (clear cell RCC) to the gynecologic tract is infrequent, and involvement of the uterus is extremely rare. A review of the literature identified a total of 12 reported examples with metastasis to the uterine serosa (1), endometrium (5), cervix (5) and only one with metastasis to the myometrium. This report represents the first case of tumor-to-tumor metastasis involving a clear cell RCC with metastasis to a uterine leiomyoma. The patient was a 50-year-old woman status post-radical nephrectomy for newly diagnosed unilateral clear cell RCC (stage pT3a) with negative margins, who subsequently underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy for the incidental finding of multiple uterine masses measuring up to 14.5 cm suggestive of fibroid on pelvic ultrasound. The pathologic exam of the specimen was consistent with metastatic clear cell RCC (1.2 cm) to uterine leiomyoma, confirmed with keratin, vimentin, CD10, CA9, and PAX8 immunohistochemistry. The patient's postoperative course was uneventful, and no new lesions were identified at follow-up during the past 6 months.

A 39-year-old woman originally from Northeast Africa sought medical attention for positional dyspnea. Computed tomography of the chest revealed an 8.5 cm hypodense anterior mediastinal mass with peripheral calcifications that raised a wide differential diagnosis including infectious and neoplastic lesions. Following surgical resection, a large cavitary necrotizing and calcified granuloma involving the thymus was identified on histopathological examination. The changes were associated with parasitic eggs that based on their morphology suggested infection due to trematode species. The diagnosis was further corroborated by identification of the increased IgG titers for Schistosoma species (ELISA Kit, NovaTec). The patient's symptoms improved following surgery and praziquantel therapy. This unique presentation emphasizes an unusual manifestation of schistosomiasis that can pose a diagnostic challenge, especially in non-endemic regions. It suggests that mediastinal involvement by schistosomiasis is likely due to an ectopic deposition of the parasitic eggs within a definitive host. Suspicion for schistosomiasis should be heightened based on patient demographics and travel to endemic areas.

Hibernoma is a relatively uncommon benign neoplasm of brown adipose tissue which usually affects head and neck region, thigh and rarely breast. There are different subtypes of hibernoma with the spindle cell-type is the least common one. Herein, we are reporting a case of this rare spindle cell hibernoma in a location which has not been previously reported: perinephric adipose tissue. This tumor was presented as a renal mass on imaging.

Ovarian-type (ie, Mullerian) epithelial tumors occurring in the testicular and paratesticular regions are exceptionally rare, with only a handful reported worldwide. Serous tumors are the most frequently encountered subtype among these rare tumors. The pathogenesis of these tumors within the testicular and paratesticular regions remains a subject of intrigue and debate, with various hypotheses attempting to explain their presence in the paratestis region, where most tumors occur. However, our understanding of the pathogenesis of intratesticular tumors is limited. To date, 11 known examples of intratesticular serous Mullerian tumors have been reported globally. In this report, we present an extraordinary tumor, an intratesticular Mullerian serous borderline tumor with foci of microinvasion, in a 38-year-old male patient. This tumor exhibits histological features similar to their ovarian counterparts and is confirmed through an immunohistochemical panel. Our report underscores the extreme rarity of these tumors, emphasizes the importance of heightened awareness among clinicians and pathologists, and provides valuable insights into their complex development and histogenesis. This contribution aims to enhance diagnostic precision and optimize therapeutic strategies for similar tumors.

Well-differentiated neuroendocrine tumor rarely occurs as a testicular primary tumor, accounting for less than 1% of all testicular cancers, and is rarely reported with sufficient molecular profiles. After searching our departmental database (2003-2023), two testicular primary well-differentiated neuroendocrine tumors were identified in a 35-year-old man and a 23-year-old man, respectively, both of whom had normal serum level of tumor markers. Both tumors grossly exhibited solid, yellow-tan, and homogeneous appearance and histologically displayed a mixture of growth patterns, including organoid, tubular, cribriform, nests, cords, and single cells, were composed of eosinophilic tumor cells with salt-and-pepper chromatin and indistinct cell borders. Immunoreactivity for chromogranin and synaptophysin were detected, with Ki-67 labeling 9% and 2% of tumor cells on counting of 500 tumor cells, respectively. There was no germ cell neoplasia in situ in the background testicular parenchyma. Furthermore, fluorescence in situ hybridization failed to identify the presence of isochromosome 12p in both tumors. A panel-based next-generation sequencing was done in one of tumors and showed no reportable pathogenic variants with a mutation burden of 0.5 mutations per megabase. Although elevated mitotic figures (up to 6 per 10 high power fields), lymphovascular invasion and marked nuclear pleomorphism were present in this tumor, there was no evidence of disease detected in this patient via Dotatate positron emission tomography/computed tomography scan after the surgery. This report expands the spectrum of testicular primary well-differentiated neuroendocrine tumor. Considering its rarity, it may pose a diagnostic challenge or pitfall in certain clinical circumstances. In addition, the literature pertaining to this entity is herein reviewed.

Undifferentiated carcinomas are highly aggressive tumors with a dismal prognosis. A subset of these tumors has been associated with inactivation or mutations of the Switch/Sucrose Nonfermenting (SWI/SNF) remodeling complex. Our understanding of the relationship between the clinicopathological features and molecular profiling of SWI/SNF-deficient undifferentiated carcinoma is still evolving due to its rarity. We herein present a rare tumor of undifferentiated carcinoma with SMARCB1/INI1 deficiency arising from the colon. The histology revealed a tumor composed of sheets of discohesive, high-grade epithelioid cells with rhabdoid morphology along with anaplastic giant cells. Additionally, there was a significant infiltration of inflammatory cells in the background. Immunohistochemical (IHC) analysis supported the diagnosis of carcinoma with loss of INI1 expression, the tumor was mismatch repair protein proficient. Molecular analysis demonstrated an oncogenic KRAS mutation (p.G12D), whereas it was wild-type BRAF, and wild-type NRAS. The diagnosis of SWI/SNF-deficient undifferentiated carcinoma can be challenging. Correlation with clinical findings, in conjunction with IHC work-up and molecular analysis, is of utmost importance to arrive at the appropriate diagnosis and exclude potential mimics.

Papillary carcinoma of the breast is a rare histologic subtype of invasive breast cancer. In contrast, ductal carcinoma in situ (DCIS) is a noninvasive, nonobligate precursor to invasive mammary carcinoma, confined within the terminal duct lobular unit of the breast and surrounded by an intact myoepithelial cell layer at the stromal/epithelial interface. We present an unusual case in which a patient with only DCIS of the breast exhibited papillary carcinoma within a sentinel lymph node, leading to questions about the origin of the lymph node lesion—whether it represents a true metastasis or iatrogenic displacement during diagnostic procedures. This case underscores the diagnostic challenges and clinical implications associated with such rare presentations.

A life-threatening complication of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection is acute respiratory distress syndrome. Our understanding of the pathologic changes in coronavirus disease 2019 (COVID-19) is based almost exclusively on post-mortem analyses of adults. These studies established several hallmarks of SARS-CoV-2 lung infection, including diffuse alveolar damage, microvascular thrombi, and acute bronchopneumonia. We describe a fatal example of COVID pneumonia in a 9-year-old girl who presented with fever 10 months following the diagnosis of ALK-positive anaplastic large cell lymphoma (ALCL). A chest computed tomography scan revealed left upper lobe lung consolidation and nodular airspace disease, and an initial SARS-CoV-2 nasopharyngeal swab (RT-PCR) was negative. A subsequent lung biopsy performed due to concern for relapsed ALCL demonstrated sheets of intra-alveolar and interstitial macrophages, and macrophage-rich fibrinous exudates. Immunohistochemical and in-situ hybridization stains confirmed these macrophages as the predominant SARS-CoV-2-infected cell type. Subsequent RT-PCR testing of upper and lower respiratory tract samples was positive for SARS-CoV-2 infection. Whole genome sequencing confirmed the presence of the B.1.617.2 (Delta) variant. This biopsy illustrates the histopathologic features of early COVID pneumonia in antemortem lung tissue from a pediatric patient, and establishes macrophages as a potential source of SARS-CoV-2 amplification.

The recent influx of novel renal neoplasms, particularly molecularly-defined renal carcinomas, has introduced new challenges in the daily practice of most pathology laboratories. These tumors are uncommon, they do not always have well-established morphologic features, and the expression profile of most common biomarkers is not well understood. Moreover, the diagnosis of molecularly-defined renal carcinomas requires the documentation of the disease-defining molecular alteration, with molecular studies or surrogate immunohistochemical markers. Unfortunately, most pathology laboratories lack molecular laboratories, or it is not cost-effective to maintain assays of the specific biomarkers in these unusual tumors. Pathologists should have updated knowledge about the recent changes in renal neoplasms and be aware of these limitations.