bluuebunny/crossref_metadata_2025 huggingface dataset:
Unusual Presentation: Nephroblastoma/Wilms tumor in an Adult – A Case Report
Authors: Pokharel A , Thorburn C , Fullmer J , Macknis J K , Zhang P L
Published: October 2024

Introduction/Objective

Nephroblastoma/Wilms tumor is a common renal tumor primarily observed in children, and its occurrence in adults is exceedingly rare. This rarity contributes to the diagnostic challenges encountered in adults.

Here, we present a case of a 32-year-old male diagnosed with biphasic nephroblastoma/Wilms tumor in the kidney, with liver and lung metastases.

Methods/Case Report

A 32-year-old male, without significant past medical history, presented with the chief complaint of abdominal pain for 2-3 weeks. Imaging studies revealed a substantial 17.5 cm kidney lesion accompanied by numerous lung and liver lesions. A liver biopsy indicated a small blue cell tumor, morphologically and immunophenotypically, (positive WT1) resembling nephroblastoma, with a strong suspicion of metastasis. Subsequent kidney biopsy confirmed a small blue cell malignant tumor demonstrating biphasic features, including blastema and epithelial components forming tubular structures similar to the liver biopsy, predominantly showing the blastemal component. The renal tumor biopsy supported the diagnosis of nephroblastoma. Despite chemotherapy, the patient passed away two months after the initial liver tumor biopsy.

Results (if a Case Study enter NA)

NA

Conclusion

Diagnosing nephroblastoma in adults poses significant challenges, particularly when initial presentations involve metastases. The occurrence of pediatric tumors in adulthood, though rare, should be considered in the diagnostic process after exhausting other possibilities. It is also important to note that the clinical presentation of pediatric tumors in adults may deviate from typical patterns. While Wilm’s tumor commonly presents as a painless, palpable abdominal mass in pediatric cases, adults may exhibit abdominal pain as the predominant symptom, as present in our case.
Metastatic Germ Cell Tumors Often Represent Continuous Evolving Processes (Somatic Transformation) toward SALL4-Positive Dominant Yolk Sac Tumors and Teratomas
Authors: Pokharel A , Metcalf B D , Qu Z , Macknis J K , Pansare V , Zhang P L
Published: October 2024

Introduction/Objective

SALL4 has been used to diagnose primary and metastatic germ cell tumors (GCT). However, it is not well established if SALL4 represents an evolving biomarker for GCT during the metastatic processes.

Methods/Case Report

We studied the fetal expression of SALL4 and a small series of metastatic GCT by comparing SALL4 expression (in all levels of GCT) with OCT3/4 expression (mainly in the early chain of germ cell tumors such as seminoma and embryonal carcinoma).

Results (if a Case Study enter NA)

First, we found SALL4 expression in Wolffian ducts and their surrounding stromal cells of 4 early embryos (5-7 weeks of gestation), implying that SALL4 may be involved in the early genital structure development. Then we identified 6 cases with metastatic GCT and compared SALL4 with OCT3/4 stains. The original tumors were all positive for both OCT3/4 and SALL4, but 4 out of 6 subsequently metastatic GCT stained positive only for SALL4 but not for OCT3/4. Particularly in case 5, the first two biopsies for metastatic GCT were positive for both biomarkers, but the last metastatic GCT to the gallbladders was positive only for SALL4.

Conclusion

Our pilot study raises the possibility that metastatic GCT may represent some evolving process to epithelial differentiated neoplasms (via somatic transformation) namely yolk sac tumor and teratoma along the germ cell differentiation chain. Therefore, SALL4 staining becomes a necessary step to avoid the pitfall of misdiagnosing unusual metastatic tumors with a known and unknown history of GCT particularly in male patients.
Diffuse Large B-cell Lymphoma (DLBCL) involving the Uterine Corpus presenting with Abnormal Uterine Bleeding: A Rare Case Report
Authors: Kumar G , Amer Y , Raja F , Wang Y , Ayub S , Youssef M
Published: October 2024

Introduction/Objective

Diffuse Large B-cell Lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma. Lymphomas affecting the female genital system are extremely rare, accounting for about 1% of extra-nodal lymphomas, with DLBCL being the most common type. We present a rare case of uterine lymphoma presenting with abnormal uterine bleeding.

Methods/Case Report

A 50-year-old female presented with abnormal uterine bleeding and fatigue for the past three weeks. Laboratory work-up showed hemoglobin level of 5.5 g/dL. Pelvic ultrasound revealed thickening of the endometrium and a 1.6 cm hypoechoic uterine lesion along with multiple enlarged bilateral adnexal lymph nodes.

Histological examination of the endometrial biopsy demonstrated endometrial fragments with diffuse subepithelial proliferation of large, poorly differentiated cells with round nuclear contours, finely dispersed chromatin, relatively inconspicuous nucleoli and moderate amount of cytoplasm. Many scattered mitoses and apoptotic bodies were present. Primary set of immunohistochemical stains were performed to rule out primary uterine epithelial or mesenchymal tumors. The tumor cells were negative for pan-keratin, high and low molecular weight keratins and positive for CD45. Further work-up demonstrated CD20 positivity. It was diagnosed as DLBCL with a non-germinal center, double expressor phenotype and a high Ki-67 proliferation. Fluorescence in-situ hybridization studies were negative for MYC and BCL6 gene rearrangements and IGH-BCL2 translocation.

Further radiological workup revealed diffuse lymphadenopathy with multiple pulmonary and renal nodules consistent with Stage IV DLBCL. She was treated with six cycles of R-CHOP regimen, and complete metabolic response was achieved.

Results (if a Case Study enter NA)

NA

Conclusion

Uterine lymphomas are very rare and on small biopsies may histologically mimic poorly differentiated uterine malignancies such as dedifferentiated/undifferentiated carcinomas. Adding lymphoma lineage markers to poorly differentiated tumors is recommended to avoid missing such a rare entity.
Decidual Granulomas in Placenta: A unique finding in Preeclamptic Pregnancy
Authors: Elkabbani R , Asad M , Fiedler P , Pathan N
Published: October 2024

Introduction/Objective

Decidual granulomatous inflammation is a rare finding in the placenta, scarcely reported in the literature. We present an unusual case of a young woman with severe preeclampsia and histological presence of decidual granuloma, involving the placental membranes.

Methods/Case Report

A 34-year-old female, Gravida 2 Para 1, with prior term vaginal delivery without significant history presented at 26 weeks and 6 days of gestational age with decreased fetal movements. Her home blood pressure was 170 mm of Hg systolic and on presentation, was consistently within the range of 192-197/94-97 mm of Hg. Biophysical profile of the fetus was 2/10. Complete blood count showed leukocytosis with absolute neutrophilia and urinalysis revealed slight increase in urine protein/creatinine ratio. Clinical diagnosis of severe preeclampsia was made. After initial stabilization, the patient underwent Cesarean section resulting in a premature baby with an uneventful postoperative course. The placenta was sent for histopathological examination. Grossly, the placental disc showed unremarkable membranes with normal appearing fetal and maternal surfaces. Sectioning revealed a central 4.2 cm hemorrhagic area and six tan-white wedge-shaped nodules ranging from 0.8-1.8 cm, occupying approximately 5% and 40% of the maternal surface, respectively. Microscopic examination revealed patchy non-caseating granulomas limited to the decidua, patchy intra-placental hematomas, placental infarcts and chronic villitis. Other findings included scattered avascular villi, villous stromal vascular karyorrhexis, focally increased syncytial knots, and decidual arteriopathy. Gram stain, GMS and acid-fast stains yielded negative results, while immunohistochemical stain CD68 highlighted histiocytes in the granulomas. The final diagnosis of decidual granulomas including the aforementioned microscopic observations was made.

Results (if a Case Study enter NA)

NA

Conclusion

Though decidual granulomas are seen in association with infectious and rheumatologic disorders. They can also be observed in severe preeclampsia as in this setting; with unclear underlying pathogenesis, warranting a close follow-up of the newborn and the mother.
Does change in endometrial carcinoma FIGO staging (2018 to 2023) matters?
Authors: Jawaid T , Vidhun R
Published: October 2024

Introduction/Objective

Endometrial Carcinoma (EC) is the sixth most common diagnosed cancer in women. Cancer related to corpus uteri are often diagnosed after menopause. TNM classification and FIGO staging system is used for staging of EC. College of American Pathologists (CAP) has been using FIGO staging system 2018 until new FIGO staging 2023 was published on June 20th 2023. We aim to identify if the new 2023 FIGO staging will change the previously assigned staging as per 2018 FIGO staging system of the endometrial carcinoma and if this change will help the physician to reevaluate the patient management.

Methods/Case Report

This is a retrospective cohort study. Total 205 cases were recruited from June 2022 till October 2023 at Danbury Hospital. All the patients of 18 years and above were selected for the study and were treated with hysterectomy for endometrial carcinoma and were reported to have FIGO staging as per 2018 CAP cancer protocol. Sixty three (63) participants were selected for the study. Exclusion criteria includes the cases diagnosed as endometrial carcinoma on biopsy, curettage, and patients who did not follow up for treatment. The data search was done on variables required to evaluate the FIGO staging for 2018 and 2023.

Results (if a Case Study enter NA)

Out of 63 patients, 55 cases were reported as per FIGO stage 2018 and eight cases were evaluated on TNM classification only. The staging did not change for forty nine (49/63) cases. However, six cases (6/63) had a change in staging based on the criteria out of which four cases (4/6) had an upstage and two cases (2/6) had a downstage.

Conclusion

Staging has a critical role in management of the patient. The updated FIGO staging includes multiple variables (including molecular) to improve the patient care who are diagnosed with endometrial carcinoma. Identifying the appropriate updated staging can be beneficial for oncologist to decide the treatment recommendation in the future.
The Importance of Recognizing Vaginal Melanoma, A Unique and Aggressive Subtype of Mucosal Melanoma with Undefined Staging and Treatment Protocols: Case Report and Literature Review
Authors: Durkin V , Jassim A
Published: October 2024

Introduction/Objective

Primary vaginal melanoma is a highly aggressive subtype of mucosal melanoma, with few cases reported in the literature. Mucosal melanomas represent a very small subset of melanoma cases, with even fewer found in the vagina. There is a frequent delay in diagnosis due to absent or nonspecific symptoms.

Methods/Case Report

We report two cases of primary vaginal melanoma that were found on biopsy due to abnormal postmenopausal bleeding. Case 1 is a 62-year-old woman that was found to have a necrotic mass originating from the vaginal apex, while case 2 is a 66-year-old woman that had a vaginal polyp. Microscopic examination of both cases revealed sheets of malignant cells with prominent nucleoli, brisk mitotic activity, and patchy melanin pigment.

Immunohistochemical stains for MART-1 and SOX10 were positive in both cases, supporting the diagnosis. The patient in case 1 had an upper vaginectomy and is currently on immunotherapy as part of a clinical trial. Further treatment and status of the patient in case 2 is unknown.

Results (if a Case Study enter NA)

N/A

Conclusion

Due to the rarity of cases, little is known about the etiology and risk factors. A standardized staging system is not yet accepted, with most using a combination of the AJCC and FIGO systems, however, neither are specific for vaginal melanomas. Patients are often metastatic at the time of diagnosis due to delayed diagnosis and aggressive nature of the disease. Specific treatment protocols have not yet been defined, and it is debated whether a more conservative or aggressive approach is favored. The disease control and survival rates are dismal with a poor prognosis. The role of adjuvant and targeted molecular therapies is still being investigated. The addition of our cases to the literature will hopefully bring more awareness to vaginal melanoma as a diagnostic possibility and encourage more research to be done.
Institutional Review and Clinicopathologic Correlation of Head and Neck Sarcomas
Authors: Berger B , Rampisela D , Buras M , Clark D
Published: October 2024

Introduction/Objective

Head and neck sarcomas are challenging to diagnose and treat. Sarcomas in the head and neck region cause significant morbidity and mortality due to the vital structures affected. The rare nature of head and neck sarcomas also creates challenges in studying these entities.

Methods/Case Report

We performed a retrospective review of 40 cases of head and neck sarcomas at our institution from January 2000 to December 2023. Cases of metastatic sarcoma to the head and neck region were excluded. Skin and thyroid primary cases were also excluded.

Results (if a Case Study enter NA)

The initial age of diagnosis ranged from 2 years to 86 years with an average age of 39.2 years old. Thirteen pediatric patients were identified with the most common diagnosis being embryonal rhabdomyosarcoma and the most common location being the pharynx. The most common diagnosis among adult patients was chondrosarcoma with the most common location being the sinuses. Most patients presented at stage T2N0M0 and had an average survival of 4.4 years. Pediatric patients had a slightly greater average survival of 8.4 years. Adult patients had an average survival of 2.1 years.

Conclusion

Overall, head and neck sarcomas show poor prognosis and arise more commonly in the pharynx in pediatric patients and the sinuses in adult patients.
Features of Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic mutation syndrome associated with the c.121A>C, p.(Met41Leu) UBA1 genetic variant: A systematic review
Authors: Mumtaz M , Khan A E , Qureshi P M , Poombal F , Bauer L J , Noor R , Malik A , Khalid M , Kamran A
Published: October 2024

Introduction/Objective

Vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic mutation (VEXAS) syndrome was first described in 2020. VEXAS is driven by a mutation in the UBA1 gene on hematopoietic progenitor cells that encodes the E1 ubiquitin-activating protein. Loss of this protein leads to various inflammatory clinical presentations ranging from dermatological, pulmonary, rheumatologic and hematologic. Many UBA1 variants have been identified. We did a systematic review focusing on a particular UBA1 variant gene mutation underlying this disease process.

Methods/Case Report

Databases were searched for articles discussing VEXAS syndrome until April 2024. Only case reports and case series in the English language were included. Data on patient demographics, clinical presentation, laboratory values, bone marrow findings, dermatologic presentation and skin biopsy findings were extracted.

Results (if a Case Study enter NA)

332 articles discussing VEXAS syndrome were retrieved, of which 115 were case reports or case series. These were screened for patients carrying a p.Met41Leu UBA1 gene mutation and only the 25 patients with this genetic variant were ultimately included in our study. The average age was 68 years (59-81 years). 24/25 (96%) patients reported dermatologic symptoms ranging from erythema to urticarial eruptions to erythema multiforme. Fever was the second most common presenting complaint (76%) followed by arthritis (68%), chondritis (36%) and thromboembolic disease (28%). Macrocytic anemia was a common laboratory finding (65%). MDS was seen in 52% of the patients. All patients had hematopoietic progenitor cells with vacuoles. Sweet’s syndrome was the most common initial diagnosis (52%) as skin biopsies in most patients showed dermal edema and neutrophilic dermatoses/infiltration.

Conclusion

The c.121A>C, p.(Met41Leu) UBA1 variant is frequently related to cutaneous manifestations. In patients with clinical features of an inflammatory disorder with dermatological and hematologic abnormalities, testing for the p.Met41Leu UBA1 mutation might lead to an earlier diagnosis and prompt initiation of effective treatment.
A Diagnostic Challenge in the Biopsy of a Mammographic Abnormality
Authors: Pham T , Rao R , Vo T
Published: October 2024

Introduction/Objective

Primary breast marginal zone lymphoma (MZL) is an uncommon subtype of extranodal lymphoma, and its diagnosis presents challenges, particularly in distinguishing it from lymphoplasmacytic lymphoma (LPL). MYD88 L265P mutation has been identified in a subset of marginal zone lymphomas, comprising 6-9% of cases. This genetic alteration further complicates the differentiation between MZL and LPL in breast tumors. We present a case highlighting the diagnostic complexities associated with primary breast MZL.

Methods/Case Report

A 71-year-old female patient underwent mammographic screening, which revealed a suspicious lesion in her left breast. Subsequent PET scan showed a hypermetabolic area consistent with a primary breast lesion. Biopsy histology exhibited a diffuse atypical lymphoid infiltration with varying proportions of neoplastic lymphocytes. Immunohistochemical analysis revealed positivity for CD20, PAX5, BCL2, CD138, MUM1, and negativity for CD3, CD5, Cyclin D1, CD10, CD23, CD34, BCL6, TDT, CD30, GATA3, and CK AE1/3. Additionally, there was lambda light chain restriction, and the Ki67 proliferation rate index was approximately 50%. Fish analysis indicated abnormal BCL6 gene rearrangement. Molecular genetic testing confirmed the presence of MYD88 mutation with c.794T>C p.L265P. Notably, bone marrow biopsy showed no abnormalities, with normal hematopoiesis. Serum electrophoresis and immunofixation detected an IgM monoclonal protein with lambda light chain specificity.

Results (if a Case Study enter NA)

NA

Conclusion

The diagnosis of primary breast MZL was favored over LPL due to the absence of common LPL- associated symptoms such as bone marrow involvement. However, the distinction between these entities remains challenging, underscoring the importance of comprehensive diagnostic approaches integrating histopathology, immunohistochemistry, and molecular genetics. Further research is warranted to enhance diagnostic certainty in such cases, particularly as the management of MZL and LPL becomes increasingly specific with the advent of novel therapeutic agents and ongoing clinical trials.
CD5+ Large B cell lymphoma with IRF4 rearrangement: case report and review of the literature
Authors: Torres Y , Shen P
Published: October 2024

Introduction/Objective

Large B cell lymphoma with IRF4 rearrangement was introduced as a diagnosis by WHO in 2017. It is a rare entity that affects Waldeyer’s ring in mostly males, children and young adults. The lesional immunophenotype may be positive for CD10. FISH is positive for IRF4 rearrangement on chromosome 6p25.Among reported cases in the English literature only 6 cases have reported specifically CD5 being negative. We present review of the literature during years 2020-2024, and a case of large B cell lymphoma with IRF4 rearrangement, specifically positive for CD5.

Methods/Case Report

The patient is a 5 years old male, since 2017 suffering from recurring ear infections with approximately 4-5 episodes of otitis media during every 6 months. In 2019 the patient’s mother reported snoring, constant sore throat, bad breath for 2 years. On physical examination the left tonsil appeared enlarged; exudative tonsillitis was present. Later on, an asymmetric, firm mass in the location of the left tonsil with induration of the left palate was identified. CT scan showed mild asymmetric soft tissue thickening of the left aspect of the soft palate and left palatine tonsil. Mildly prominent left-sided levels IIa and IIb lymph nodes, measuring up to 1 cm were identified. H&E sections revealed an expansile proliferation of neoplastic cells, large with void to indented nuclei, vesicular chromatin, small nucleoli, visible cytoplasms. Frequent mitoses, apoptosis and individual cell necrosis were seen.

Immunohistochemistry revealed CD20+ B cell neoplasm with high expression for MUM1 and high proliferation rate along with strong CD5+ and CD10-. By multicolor flow cytometric studies, an abnormal B cell population was found (40%) with increased forward scatter along with expression for CD5, CD19, CD20, CD22, CD45, CD79a (cytoplasmic), FMC7, (dim) lambda-restriction. Fluorescence In Situ Hybridization Study revealed IRF4 (DUSP22) rearrangement on chromosome 6p25.

Results (if a Case Study enter NA)

NA

Conclusion

We analyzed 24 cases reported in the English literature. The mean age of the patients is 7 years old. The majority are males (14/24 = 58%).The most common location is tonsil/ neck mass (15/24 = 62%).CD5 was negative in 6/24 cases.
Hemophagocytic Lymphohistiocytosis as an Unusual Presentation in a Patient with Human Immunodeficiency Virus-associated Bone Marrow Classic Hodgkin Lymphoma: A Case Report with Literature Review
Authors: Rivera Sustache J M , Jetly R
Published: October 2024

Introduction/Objective

Compared to the general population, people living with human immunodeficiency virus (HIV) have a higher incidence of lymphoproliferative disorders including classic Hodgkin lymphoma (CHL). Hemophagocytic lymphohistiocytosis (HLH) triggers in HIV patients include HIV itself and HIV-associated malignancies or infections, all of which can have many overlapping symptoms, causing diagnostic challenges and delays in initiating treatments.

Methods/Case Report

A 56-year-old HIV-positive man presented with septic shock-like symptoms, pancytopenia, hyperferritinemia, transaminitis, elevated IL2-receptor alpha and hepatomegaly. Mild retroperitoneal lymphadenopathy found on imaging yielded non-diagnostic biopsies. A bone marrow (BM) biopsy showed no malignancy or disseminated infections and a rare hemophagocyte. Treatment for HIV-triggered HLH lead to a marked clinical improvement. Three months later he presented with worsening symptoms, negative cultures, and an EBV+ CHL on a BM biopsy. Mild increase in lymphadenopathy and multiple liver/spleen hypodensities found on imaging could not be biopsied due to rapidly deteriorating patient’s condition and death.

Results (if a Case Study enter NA)

NA

Conclusion

Per studies, HLH is more frequent in the HIV-associated lymphomas compared to the non-HIV- associated ones, usually presenting as a sepsis-like syndrome in these patients. Probability of HLH development was particularly high with BM involvement and CHL. From 2010, seven cases of HIV-associated CHL presenting with HLH were found in the literature with these findings: (n=8, including ours) sex- all males; average age- 45 years (range 28- 64); average HIV viral loads- 83,369 copies/mL (range: undetectable->300,000); average absolute CD4 count- 98 cells/microliter (range: 8-314); interval from HIV diagnosis- new to 26 years; anti-retroviral treatment- 6; symptoms- fever (all), other symptoms were variable; HLH-2004 protocol criteria- all; biopsy-proven hemophagocytes- 3; EBV+ CHL- all (6 were diagnosed on BM biopsies); outcomes- remission (2), response to treatment (4), death (2). CHL- triggered HLH in HIV patients is a complex diagnostic entity. A high index of suspicion and thorough investigations including early BM biopsies can ensure better outcomes.
A Case of Idiopathic Multicentric Castleman Disease Developing in a Patient with a History of Biopsy Proven Membranous Nephropathy
Authors: Chinchanikar S , Lankachandra K , Galbraith R
Published: October 2024

Introduction/Objective

Idiopathic multicentric Castleman disease (iMCD) is a lymphoproliferative disorder involving two or more lymph node sites. It is usually associated with systemic inflammatory symptoms and organ dysfunction related to hypercytokinemia. Renal involvement in iMCD has only been described in a limited number of studies and case reports. Of note, only one previous case report has described results from renal biopsies taken prior to the development of iMCD.

Methods/Case Report

Our patient is a 43 year old female who was first diagnosed with membranous nephropathy in early 2020. She had PLA2 R negative and Exostosin-2 positive disease. Age appropriate screening for malignancy was unremarkable. She had positive ANA titres and normal complement levels but did not meet criteria for SLE per rheumatology. Her proteinuria was improved and maintained on Lisinopril for 3 years. In October 2023, her proteinuria suddenly increased. Repeat renal biopsy was unchanged from the initial biopsy. This time, she also noticed acute swelling over her subpectoral region. PET-CT scan revealed multiple areas of avid lymphadenopathy on either sides of the diaphragm but the highest yield PET- avidity was in the subpectoral region. Biopsy of the right subpectoral lymph node was performed. According to the WHO Classification, 5th edition, diagnostic criteria for iMCD-NOS was met with the histological features displaying grade 3 plasmacytosis, grade 2 regressed germinal centers, follicular dendritic cell prominence, increased hyperplastic follicles and increased vascularity. Immunohistochemical staining for CD138 highlighted abundant plasma cells, CD21 highlighted follicular dendritic cell prominence. Vascular proliferation was seen by CD34 staining. Kappa and Lambda- ISH demonstrated polytypic staining pattern and HHV-8 was negative.

Results (if a Case Study enter NA)

NA

Conclusion

There is a significant clinical, histologic and immunologic overlap between iMCD, autoimmune or infectious disorders and malignancy. HHV-8 negative/iMCD is less well understood and has no specific biomarkers. It is important to follow the available clinicopathologic diagnostic criteria for early diagnosis, follow up and treatment.

Timely recognition can help prevent multiple organ system dysfunction, systemic inflammatory symptoms, cytopenias and polyclonal lymphoproliferation. Although the pathophysiology maybe unclear, this case may also suggest that in patients with a previously diagnosed membranous nephropathy, iMCD may play a role in recurrence and worsening of the disease.
Biological Adaptations in Rhabdomyosarcoma Tumor Cells in lymph nodes: A Case Report of RMS with FUS::TFCP2 translocation
Authors: Zhou X , Feng Y , Husson M
Published: October 2024

Introduction/Objective

The WHO classification categorizes Rhabdomyosarcoma (RMS) into four main subtypes based on clinicopathological and molecular features. However, TFCP2-rearranged RMS, a rare tumor, does not neatly fit into any of these subtypes. Literature review identified only two reported cases of RMS with FUS::TFCP2 fusion and a round cell component.

Methods/Case Report

We present a rare case of RMS in lymph nodes with FUS::TFCP2 translocation in a 29-year- old female with a history of spindle cell rhabdomyosarcoma in the bilateral maxilla. The original tumor exhibited a distinctive spindle and epithelioid phenotype, coexpressing myogenic markers, epithelial markers, and ALK. FUS::TFCP2 translocation was confirmed, representing an uncommon subset of RMS. After chemotherapy, radiation, and surgery, the patient developed multiple bilateral pathologically enlarged cervical lymph nodes. Excision revealed metastatic rhabdomyosarcoma involving lymph nodes with a predominantly round cell and epithelioid morphology, with approximately 5% spindle cell growth, resembling the pattern identified in the primary resection.

Results (if a Case Study enter NA)

NA

Conclusion

Previous reports suggest that RMS with FUS::TFCP2 fusion displays a biphasic pattern, comprising solid proliferation of round cells in superficial areas and spindle cells in deeper regions. The altered cell morphology observed in our case may be attributed to the varied distribution pattern of each component with lesion depth and the cellular stress response. Previous literature reported that radiation stress potentially leads to biological adaptations of tumor cells and tumor radioresistance. Our findings underscore the distinctive phenotype of RMS with FUS::TFCP2 fusion, characterized by the coexpression of myogenic and epithelial markers, along with ALK positivity.

Understanding the cellular adaptations of RMS cells could inform the development of novel clinical interventions aimed at enhancing radiosensitization and improving therapeutic efficacy, ultimately enhancing patient survival.
Primary Cutaneous Acral-type CD8-positive T-cell Lymphoproliferations: Widely Divergent Clinical Outcomes Despite Nearly Identical Histomorphology
Authors: George G V , Scott G , Syposs C R , Evans A G , Casulo C
Published: October 2024

Introduction/Objective

Non-epidermotropic and acral CD8(+) T-cell proliferations have recently been reclassified as lymphoproliferative disorders (LPDs) due to their indolent course clinical. Here, we describe two cases with similar histomorphology but disparate clinical outcomes, highlighting the diagnostic challenges.

Methods/Case Report

Case 1: An 89-year-old male developed a 2 cm erythematous papule on the forehead. Biopsy showed a non-epidermotropic pan-dermal lymphocytic infiltrate, a distinct grenz zone, and areas of necrosis.

Case 2: A 53-year-old male presented with a rapidly growing, ulcerating 8.9 cm scalp lesion. Biopsy showed a deep dermal lymphoid infiltrate with complete epidermal sparing. In both cases neoplastic cells were positive by immunohistochemistry for CD2, CD3, CD5, CD7 (partial), CD8, granzyme B, TIA-1, and CD68 (perinuclear dot-like pattern). The Ki-67 proliferation index varied modestly between cases (50% in case 1 and 70% in case 2, respectively). Despite treatment, within the span of a few months, case 2 developed adjacent, widely distributed scalp nodules with extensive local tissue destruction. Pathology was consistent with recurrent disease (flow cytometry demonstrating T-cells, co-expressing CD8, CD2, CD3, CD5, CD7 and monotypic TRBC1).

Results (if a Case Study enter NA)

NA

Conclusion

CD8+ T-cell lymphoproliferative disorders, specifically primary cutaneous acral CD8+ T-cell lymphoproliferative disorder, is a rare cutaneous T-cell disorder that was re-classified, owing to its indolent clinical course, low risk of systemic dissemination, and favorable prognosis. We report two cases of nearly identical isolated cutaneous lesions that demonstrated a CD8(+)-cytotoxic phenotype with CD68-dot-like positivity. Although all morphologic findings were supportive of the diagnosis, the aggressive clinical progression in case 2 highlights the potential for the disease to defy the classically described indolent behavior. Given that few cases with aggressive clinical courses have been published, we present these cases to underscore their complexity and propose that the classification incorporate clinicopathological correlation to guide management.
The Vital Role of Special Stains in Immunocompromised Cases: A Focus on Histoplasmosis Screenings for Enhanced Kaposi`s Sarcoma Diagnosis Beyond H&E Morphology
Authors: Robinson B , Habecker J , Lukande R , Cherepow L
Published: October 2024

Introduction/Objective

This case report emphasizes the critical importance of thorough pathology-based investigation before making a definitive diagnosis of Kaposi’s Sarcoma (KS). In particular, we demonstrate the importance of using special stains in addition to H&E staining to determine if the lesion is KS or a fungal infection, specifically cutaneous Histoplasmosis. This highlights the necessity of comprehensive diagnostics to ensure accurate and timely identification of underlying conditions, guiding appropriate treatment strategies.

Methods/Case Report

In Kampala Uganda, a 56-year-old male with a history of HIV/AIDS presented with skin lesions on the lower extremities. The lesions were initially suspected to be Kaposi’s Sarcoma due to their appearance and the patient’s immunocompromised status. Skin biopsy results supported the initial suspicion, showing spindle cell proliferation in the dermis, a common feature of KS. Given his compromised immune system, it was imperative to conduct a thorough investigation to rule out potential etiologies, including opportunistic infections. Additional tests, including a Grocott Methenamine-Silver Nitrate stain, revealed the presence of Histoplasmosis. The patient did not exhibit typical symptoms of Disseminated Histoplasmosis, such as respiratory distress or fever. Resource constraints hindered comprehensive follow-up, impacting long-term outcome assessment.

Results (if a Case Study enter NA)

NA

Conclusion

Histoplasmosis is widespread in Africa, accounting for 61% of global cases, with 87% concentrated in Western and Central Africa. The coexistence of KS and Histoplasmosis poses diagnostic challenges due to overlapping clinical manifestations. KS primarily affects the skin, while Histoplasmosis causes invasive vascular and pulmonary infections. However, in Africa, notably in immunocompromised individuals, histoplasmosis can cause cutaneous infections. Failure to recognize and address fungal infections may result in delayed or inappropriate treatment, exacerbating the patient’s condition. This case report underscores the importance of maintaining a high index of suspicion for opportunistic infections in this population for timely intervention.
Road to automated urinalysis analyzer: Validation of Sysmex UN-3000 to supplant manual urinalysis
Authors: Walczak M , Boisvert D , Maharjan A S
Published: October 2024

Introduction/Objective

Traditionally, urinalysis encompasses the chemical analysis of urine by dipstick and manual microscopy for formed elements. High specimen volume and varying subjectivity among individuals performing microscopic analysis make the practice both imprecise and inefficient. Implementation of Sysmex UN- Series™Automated Urinalysis (Sysmex Corporation, Kobe, Japan) fulfilled our need for automation, addressing both issues at hand. Automated urinalysis offers a solution for laboratories to meet the growing demand for faster result turn around times(TAT) with ever increasing specimen volumes. We expect greater sensitivity and reproducibility in terms of comparison to manual microscopy, as well as quicker TAT with the change in methodology.

Methods/Case Report

Using both unpreserved and preserved urine tubes, a macroscopic comparative study between Clinitek Advantus(manual) and Clinitek Novus (automated) methods was carried out on 141 urines with greater than 60 abnormal patients. Similarly, a microscopic study between the laboratory’s manual microscopy procedure and the Sysmex UF-5000 was carried out on 112 urines with greater than 60 abnormal patients. RBCs, WBCs, Epithelial cells were evaluated under high power field(40X); casts and crystals were evaluated under lower power field(10X). The Reference Range Interval for both chemical and microscopic was verified using 44 normal patient specimens. The quantified values are converted to high and low power field (hpf/lpf), analogous to the current system in the laboratory.

Results (if a Case Study enter NA)

Most parameters had >90% agreement between manual and automated method. Parameters falling below 90% were checked to see if discrepancies fell within 1 degree. Automated system is more sensitive than manual and our average TAT for urinalysis dropped 50%.

Conclusion

The automated urinalysis technology enabled us to focus only on samples requiring intervention based on pathological criteria, resulting in reduced overall TAT and workload burden, and improved consistency in reporting across specimens.
Detecting and Reporting Extended Spectrum Beta-Lactamases Producers: Evaluation of Three Approaches and the Clinical Impact
Authors: Swanson K J , Nault D , Demessie G , Mendoza S , Yee R , Nagao P
Published: October 2024

Introduction/Objective

Since the COVID-19 pandemic, bacteria producing extended spectrum beta-lactamases (ESBLs) have increased >30%. Laboratories can perform phenotypic microbroth dilution or molecular approaches to identify ESBL producers. However, the gold standard is a laborious double disc synergy test. We evaluated the concordance among the three approaches, the clinical impact, and justification of reporting ESBL producers.

Methods/Case Report

Seventy-eight ESBL producers identified by microbroth dilution (MicroScan WalkAway, Beckman Coulter, Brea, California, USA) or detection of blaCTX-M gene from blood cultures (BCID2 Panel, BioFire, Biomerieux, Salt Lake City, Utah, USA) were tested using double disc synergy test retrospectively. Concordance among the methods evaluated. Discordant cases were reviewed with subsequent patient chart review.

Results (if a Case Study enter NA)

Tested isolates included E. coli (n=44, 57%), K. pneumoniae (n=19, 24%), K. oxytoca (n=7, 9%), and P. mirabilis (n=8, 10%). Concordance between microbroth dilution and disk diffusion was 86% (67/78). For isolates with genotypic testing (n=16), concordance with microbroth dilution and disk diffusion was 93% and 88%, respectively. Overall concordance was 88%. There were 12 isolates (E. coli:8, P. mirabilis: 2, and K. pneumoniae:2) with discordant results from one method. The susceptibility profile of discordant isolates revealed resistance to ceftriaxone or ceftazidime (11/12), penicillin (11/12), and aztreonam (6/12); 10/12 isolates were resistant to at least 2 groups of these antibiotics, a phenotype of ESBL producers. Clinical teams acknowledged presence of ESBLs in 83% (10/12) of cases and 58% (7/12) warranted treatment with meropenem or combinational therapy.

Infection prevention implemented contact isolate procedures in all cases.

Conclusion

Our current in-house methods (e.g., microbroth dilution and genotypic testing) are still justified for ESBL testing to optimize patient care in a timely fashion. In the minor cases with discordant results, clinical care was unaffected. Laboratory workflow changes need to take laboratory efficiency, patient outcomes, and actionable clinical changes into consideration.
Pathogenesis of Klebsiella Pneumoniae Induced Proteinopathy is Amyloid Strain Dependent
Authors: Hanna S , Morrow A , Voth S , Morrow R , Choi C , Lin M , Stevens T , Pittet J , Wagener B
Published: October 2024

Introduction/Objective

The World Health Organization has labeled Klebsiella pneumoniae (KP), a Gram-negative bacterium, as a ‘Critical Priority’ pathogen due to its increasing prevalence in serious conditions like pneumonia and sepsis, along with its growing resistance to multiple drugs. Infections with KP have been linked to the collapse of microtubules and the release of harmful proteins called amyloid-beta (Aβ) and tau from lung endothelial cells. These infection-induced lung endothelial amyloids can spread like prions and are stable under heat.

Methods/Case Report

However, the mechanisms behind these effects and whether the infection-generated proteinopathy depends on tau and/or Aβ were not well understood. This study hypothesized that KP infection triggers tau dysfunction, breakdown of microtubules, increased lung barrier permeability, and the production and release of toxic amyloids. To test this, researchers used CRISPR/Cas9 technology to create lung endothelial cells without tau and/or amyloid precursor protein (APP). They confirmed gene deletion through various methods and exposed these cells, along with regular cells, to a highly virulent KP strain.

Results (if a Case Study enter NA)

The results showed that the KP strain (Kp 1-008) caused disruption of cellular structures, increased permeability, and bacterial spread within hours of infection. Supernatants containing proteins from infected cells, when applied to healthy cells, led to barrier disruption, permeability, and cell death. Interestingly, different pathologies were induced by supernatants from cells lacking tau or APP, indicating that either tau or Aβ alone could propagate damage in a strain- specific manner. The most severe damage required both tau and Aβ together.

Conclusion

In conclusion, KP infection disturbs cellular structures, promoting barrier breakdown and bacterial dissemination. It also generates toxic tau and Aβ proteins. Either of these proteins can spread harm from cell to cell, but together, they enhance the severity and potency of the resulting lung endothelial protein damage caused by the infection. The study sheds light on the complex mechanisms of KP-related infections and their impact on cellular structures and protein pathways.
Rare Case of Subcutaneous Phaeohyphomycosis Caused by Exophiala jeanselmei
Authors: Aravind A , Sharma P , Jhaveri T , Pridmore C , Sontakke S , Smith D
Published: October 2024

Introduction/Objective

Phaeohyphomycosis is a neglected tropical infection caused by dematiaceous fungi containing melanin in their cell wall. Currently, the prevalence of phaeohyphomycosis is very low in the United States compared to other mycotic agents. Trauma often precedes phaeohyphomycosis, and there are a limited number of cases associated with healthcare settings. This case report describes a nosocomial phaeohyphomycosis caused by Exophiala jeanselmei.

Methods/Case Report

A 60-year-old male with multiple myeloma, on immunosuppressive therapy, presented with a large fluctuant mass on the dorsum of his right hand. The mass had developed 6 months ago as a hematoma following a blown vein during a blood draw. Despite treatment with antibiotics, the mass continued to grow. The patient underwent surgical excision of the lesion, and the purulent aspirate was sent to the microbiology lab. Aerobic, anaerobic, mycobacterial, and fungal cultures, along with Gram and AFB stains, were performed. Direct microscopy of the aspirate revealed numerous leukocytes and few yeast cells. No sclerotic bodies were observed. Fungal growth with black pigmentation was observed during the second week of incubation. Colonies initially appeared smooth black and mucoid, later transforming into raised dome-shaped structures with a suede-like texture. Microscopic analysis revealed budding yeast cells and subglobose to broadly ellipsoidal germinating cells, which developed into short torulose hyphae before gradually transforming into unswollen hyphae. The isolate was further identified through D2 rDNA sequencing, revealing a 100% match for Exophiala jeanselmei. The patient was prescribed a one-month course of itraconazole treatment. The patient is progressing well during follow-up.

Results (if a Case Study enter NA)

NA

Conclusion

This case emphasizes the need for heightened clinical awareness in diagnosing phaeohyphomycosis, particularly in healthcare environments. Unique traumatic events like venepuncture should raise suspicion of phaeohyphomycosis. Culture and molecular diagnostics play a crucial role in confirming fungal causes and guiding treatment, leading to better patient outcomes.
Assessing the Feasibility of a Cancer Biomarker Testing Navigator in the Laboratory
Authors: Pineault L , Valencia K , Buhay J , Brown A , Spiczka A , Ziemnik S , Kelly M , Morgante J , Datta Mitra A , Yanamura L P , Gilliland M , Ferea A , Kim J
Published: October 2024

Introduction/Objective

Cancer biomarker testing is a crucial component of precision oncology, as it can guide medical treatment decisions with targeted therapies and immune checkpoint inhibitors. However, complex, fragmented, and inefficient operational processes involved in biomarker testing lead to delays, errors, and variability in testing. One potential solution is to introduce a novel role in the pathology laboratory: the cancer biomarker testing navigator (BTN).

Methods/Case Report

The American Society for Clinical Pathology (ASCP) conducted a mixed-methods project to assess the current state of biomarker testing operations and explore how a BTN may improve biomarker testing processes. ASCP conducted an online survey, focus groups, and worked with two hospital-based cancer centers on a feasibility pilot.

Results (if a Case Study enter NA)

Survey and focus group insights reveal several operational challenges around the biomarker testing process. 47 completed the survey and 16 participated in the focus groups. Participants report that biomarker test orders may be incorrect or incomplete. 37% of survey respondents experience delays preparing tissue samples for send-out cancer biomarker testing. 42% of survey respondents are unable to track the processing status of send-out tests. Excessive time is required to coordinate and facilitate send-out tests, especially when multiple reference laboratories are used since each has its own portal, requisition form, specimen requirements, etc. 87% agree they would benefit significantly from having a dedicated person to coordinate and manage cancer biomarker tests.

The cancer centers that piloted this role found that they could catch and correct defects such as incorrect test ordered, incorrect specimen types marked on the test order, outdated requisition used, etc. The BTN also found instances where the test report was incomplete or had not been uploaded into the EHR.

The BTN role could be justified by evaluating metrics such as task efficiency, workplace satisfaction in the lab, and levels of service satisfaction from oncologists. Patient care can be improved by reducing delays in testing and by reviewing other metrics of quality care delivery.

Conclusion

The BTN role in the laboratory is a novel solution for ensuring the proper collection and triage of pathology samples for biomarker testing. This role could serve as a liaison between the laboratory and ordering clinicians, provide collection and testing guidance, and help with benchmarking and quality measurement initiatives.