bluuebunny/crossref_metadata_2025 huggingface dataset:
Splenic Epidermoid Cyst arising within an Intrapancreatic Accessory Spleen Masquerading as a Pancreatic Mucinous Cystic Neoplasm-a diagnostic enigma
Authors: Kakodkar P , Diudea D , Kanthan R
Published: October 2024

Introduction/Objective

Accessory spleens are congenital embryological aberrations usually found within the splenic hilum with no clinical significance. An IntraPancreatic Accessory Spleen (IPAS) is an uncommon benign pancreatic lesion encountered clinically. A splenic epidermoid cyst arising within an IPAS is exceedingly rare and is discussed below.

Methods/Case Report

A 68-year-old male presented with intermittent post-prandial epigastric pain radiating to the left flank for >1.5 years. Radiological imaging identified a 5.2 cm calcified cyst in the pancreatic tail with a differential of mucinous pancreatic neoplasm/ pancreatic pseudocyst. Additionally, a 2.8cm lobulated solid hypoechoic mass was seen at the porta hepatis with a differential of enlarged lymph node/benign neoplasm. Laboratory biochemical tests were within normal limits except for mildly elevated ferritin. Fine needle aspiration biopsy was indeterminate. The patient elected to proceed with surgical resection. A laparoscopic distal pancreatectomy with splenectomy and excision of the hilar mass was performed. The hilar mass was analyzed by hematopathology and revealed a hyaline- vascular variant of Castleman disease. On gross examination of the distal pancreatic/splenectomy specimen, a well- demarcated cystic lesion with brownish fluid was noted within the pancreatic tail. Microscopic examination revealed a nonpathological pancreas separated by a fibrous capsule with a large cyst arising within an intrapancreatic accessory spleen. The cyst was lined with multilayered non-keratinized CK5/6, and p63 positive squamous epithelium with no lymphocytic infiltrates and absent hair/ dermal appendages confirming a splenic epidermoid cyst. Post-operative follow-up at 6 weeks was uneventful.

Results (if a Case Study enter NA)

NA

Conclusion

An epidermoid cyst arising within an intrapancreatic accessory spleen (ECIAS) is extremely rare thus precluding accurate preoperative diagnosis as this entity shares similar radiological imaging characteristics as other cystic lesions such as mucinous pancreatic cysts. It is important for anatomic pathologists to recognize and consider the intrapancreatic compartment as a possible location for accessory spleens. Accurate preoperative diagnosis can prevent unnecessary surveillance and/or extensive surgical resection.
EVERY KERATIN-POSITIVE MALIGNANT TUMOR IN THE ADRENAL GLAND IS NOT METASTATIC CARCINOMA- A CASE REPORT
Authors: Wade C , CHAUDHARY R , Maheshwari T , Manucha V
Published: October 2024

Introduction/Objective

Angiosarcoma is a rare subtype of sarcoma arising from the vascular endothelial cells. Primary adrenal angiosarcoma (PAA) is an exceedingly rare entity, with only 53 cases documented in the literature so far.

Methods/Case Report

A 78-year-old female presented with left upper quadrant abdominal pain and early satiety. A computed tomography scan of the abdomen revealed a 15 x 13 x 16 cm, heterogeneous enhancing mass with interspersed calcifications, possibly originating from the left adrenal gland. The mass was found to be displacing the spleen and the left kidney. An ultrasound-guided biopsy of the mass was inconclusive, and the patient subsequently underwent resection of the left retroperitoneal mass, left adrenalectomy, splenectomy, and left partial nephrectomy. Gross examination revealed a slightly ruptured, red-brown mass (19.5 x 12.7 x 12.6 cm, 1784g), which was serially sectioned to reveal diffusely hemorrhagic and necrotic cut surfaces. On microscopic examination, the tumor was almost entirely hemorrhagic and necrotic, with a few viable areas that were composed of solid sheets of markedly pleomorphic epithelioid cells with a high nuclear-cytoplasmic ratio, prominent nucleoli, and increased mitotic figures. There were also a few ectatic vascular spaces lined by these markedly pleomorphic epithelioid cells.

Immunohistochemical stains of the tumor cells showed positive results for cytokeratins, CD31, ERG, and friend leukemic integration 1 (FLI-1), while Inhibin and SF-1 were negative. A diagnosis of epithelioid angiosarcoma was rendered.

Results (if a Case Study enter NA)

NA

Conclusion

PAA can be difficult to diagnose since it is rare, and thus it is not typically considered in the initial differential diagnosis. Most PAA have an epithelioid morphology, and they frequently test positive for cytokeratins. Biopsy diagnosis can also be challenging, as the mass may exhibit extensive necrosis and hemorrhage. Considering its rarity, large adrenal masses with heterogeneous features on imaging PAA should be considered as a differential diagnosis.
Exploring Immunohistochemical Profiling in High-Grade Endometrial Stromal Sarcoma - A Case Study
Authors: Jain D , Ballouk C
Published: October 2024

Introduction/Objective

High grade endometrial stromal sarcoma (HGESS) is a rare and aggressive tumor of endometrial stromal origin comprising about 0.2% of all uterine malignancies. It is often misdiagnosed preoperatively as uterine leiomyoma, leiomyosarcoma or endometrial carcinoma due to lack of well defined clinical and radiological features. We present an unusual case of HGESS with fibroid uterus and abnormal vaginal bleeding.

Methods/Case Report

A 73-year-old female with a past medical history of uterine fibroids presented with abnormal vaginal bleeding for 6 months. Her MRI uterus revealed enlarged uterus measuring 6.8 X 9.9 X 9.3 cm, multiple fibroids, and endometrial thickness of 4 mm. Hysteroscopic dilation and curettage revealed endometrial polyp and submucosal fibroid. Histopathology of submucosal fibroid revealed loosely cohesive tumor cells with high nuclear/cytoplasmic ratio, scant cytoplasm, and large prominent nucleoli, arranged in solid sheets with myxoid stroma. No glandular formation was identified. Tumor cell necrosis, bizarre tumor cells, and markedly increased mitotic activity, including atypical mitotic figures were present. Immunohistochemistry (IHC) revealed tumor cells diffusely positive for smooth muscle actin, CD10, p53, negative for AE1/AE3, CK7, cam5.2, EMA, ER, PR, desmin, and caldesmon. Ki-67 labels close to 50% of the tumor cells. Combined morphologic and IHC features favored the diagnosis of high-grade sarcoma, including leiomyosarcoma and HGESS. However, the possibility of carcinosarcoma (CS) could not be ruled out. Patient underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy.

Final histopathological diagnosis revealed HGESS, pT1b. Lack of carcinomatous component and negative IHC staining for CK7, CAM 5.2, AE1/AE3 ruled out CS. IHC showed tumor cells diffusely positive for CD10, actin, desmin and CD 56, focally positive for caldesmon, cyclin D1 and CD 117 and negative for DOG 1, further supporting the diagnosis for HGESS over leiomyosarcoma.

Results (if a Case Study enter NA)

NA

Conclusion

Definitive diagnosis of HGESS is achieved through histology and IHC. An appropriate panel of IHC markers is essential to differentiate between endometrial stromal tumors from leiomyosarcoma and CS. Accurate diagnose of this rare clinical entity is critical especially in its initial stages owing to its poor prognosis and aggressive nature.
Conclusive evidence for the origin of the carcinoid component in strumal carcinoids and a new morphological pattern
Authors: Liu Y , Feroze A , Yang L , Balakrishnan R
Published: October 2024

Introduction/Objective

There has been debate whether strumal carcinoids are carcinoids with areas resembling thyroid or arise from bonafide thyroid tissue in struma. While the thyroid nature has been proven by demonstrating positive TTF-1 in the struma component, evidence for the origin of the carcinoid component is sparse. Herein, we describe a case of strumal carcinoid and use a panel of markers to show definitive morphological and immunohistochemical evidence of the evolution of the neoplasm from struma ovarii to struma carcinoid, within the same lesion. We also report a unique component of a more sinister single cell pattern of invasion apart from the usual insular, trabecular, and mucinous patterns.

Methods/Case Report

A 40-year-old woman with an adnexal mass underwent bilateral salpingo- oophorectomy/hysterectomy. Microscopic analysis identified thyroid tissue consistent with struma ovarii, juxtaposed with a neuroendocrine neoplasm. The interface between the two showed strong PAX-8 and uniform TTF-1 staining in the struma but gradual loss of TTF-1 with retained/weak PAX-8 staining, moving away from the struma component and into the carcinoid. Additionally, a pattern of single cell invasion was identified, away from the main tumor and at the ovarian surface. These cells closely resemble luteinized ovarian stromal cells but are stained like the carcinoid tumor. Two months postoperatively, the patient had no evidence of recurrence or metastasis.

Results (if a Case Study enter NA)

NA

Conclusion

We have provided conclusive morphological and immunohistochemical evidence that strumal carcinoid develops from native neuroendocrine cells of thyroid tissue in struma ovarii. Specifically, retained/weak PAX-8 with interspersed TTF-1 in an adnexal carcinoid provides valuable insight when dealing with tumors of unknown etiology, strongly favoring an ovarian primary (specifically, from struma ovarii) and not metastasis from the gastrointestinal tract or other Mullerian tissue. Lastly, the single cell pattern of invasion that we elucidate here is something to be aware of in the context of metastases or frozen sections.
PERITONEAL KERATIN GRANULOMAS MIMICKING PERITONEAL CARCINOMATOSIS: A POTENTIAL DIAGNOSTIC PITFALL
Authors: ANAND S , Muhammad A , Haeggstroem M , Fiedler P
Published: October 2024

Introduction/Objective

Keratin granulomas from a primary uterine cancer can present as peritoneal tumor nodules, mimicking peritoneal carcinomatosis. Endometrial adenocarcinomas with viable peritoneal tumor implants and/or involvement of bladder or bowel mucosa are categorized as stage IV disease. We present a rare case of endometrial adenocarcinoma of the uterus with squamous differentiation and multiple peritoneal nodules of keratin granulomas, masquerading as peritoneal carcinomatosis.

Methods/Case Report

A 68-year-old female with insignificant past medical history presented with complaints of postmenopausal bleeding for the past four months. Physical examination was unremarkable. Transvaginal ultrasound showed a 4.9 cm echogenic mass in the uterus. The endometrial biopsy showed squamous debris with atypical cells suspicious of malignancy. Endometrial curettings revealed endometrial adenocarcinoma, endometrioid type with squamous differentiation, FIGO Grade 1. Subsequently, she underwent hysterectomy with bilateral salpingo- oophorectomy. Intraoperatively, multiple suspicious nodules on the sigmoid colon and in the pelvis were identified, of which excisional biopsies and pelvic peritoneal washing were taken. Microscopic examination of the resection confirmed endometrial adenocarcinoma, FIGO Grade 1, nuclear grade 1, with extensive foreign body giant cell reaction to dead squamous cells (ghost cells). Cytologic examination of the peritoneal washing was unremarkable and excisions of the sigmoid serosal and peritoneal nodules showed pink eosinophilic laminated nodules surrounded by inflammatory cells including plasma cells, lymphocytes and multinucleated giant cells without any viable tumor cells.

Results (if a Case Study enter NA)

NA

Conclusion

Keratin granulomas are a foreign body reaction to keratin deposition from the squamous component of endometrioid adenocarcinoma. The pathogenesis of this foreign body response to keratin is considered to be a trans- tubal spread of keratin through retrograde shedding from the fallopian tubes. In the absence of viable tumor cells, it appears to have no negative prognostic significance. Careful microscopic examination of peritoneal keratin granulomas is imperative to avoid erroneous upstaging of the tumor and the subsequent advanced treatment.
A Case Series of a Rare Parotid Gland Oncocytic Mucoepidermoid Carcinoma
Authors: Gupta D , Smith W , Shaar M , Baloi D
Published: October 2024

Introduction/Objective

We analyzed two cases of oncocytic mucoepidermoid carcinoma (OMEC) of the parotid gland which highlight the diagnostic challenges of oncocytic salivary gland neoplasms. OMEC’s are a rare type of salivary gland tumor commonly arising from the parotid gland that can easily be mistaken as benign. Proper pathologic diagnosis of these masses is critical, as it guides therapeutic intervention and has prognostic significance.

Methods/Case Report

In this case series, two patients were analyzed retrospectively for unilateral parotid masses.

Results (if a Case Study enter NA)

In a 67-year-old female, an MRI and biopsy were performed. Only a differential diagnosis could be provided, which favored oncocytoma or oncocytic carcinoma. Due to this uncertainty, a complete excision of the mass was performed. Considering the cytomorphology, immunohistochemistry (CK5/6 and P63 in oncocytes), and mucicarmine special stain highlighting scattered mucocytes, the patient was diagnosed with a low- grade OMEC. In our second case, an 80-year-old female, FNA of a posterior left ear mass 1 year prior revealed a low- grade oncocytic proliferation. With the presence of a left parotid mass one year later, additional imaging was performed and showed increased T2 hyperintensity on MRI, which caused concern for the clinicians. A superficial limited parotidectomy was performed and a differential of oncocytoma versus oncocytic variant of mucoepidermoid carcinoma was rendered. Further tumor characterization with fluorescence in situ hybridization (FISH) demonstrated a MAML2 translocation which guided diagnosis of OMEC.

Conclusion

With approximately 30% of all malignant salivary gland tumors being constituted by mucoepidermoid carcinoma, the ability to accurately diagnose even this rare subtype, oncocytic mucoepidermoid carcinoma, is of significant importance and relevance to pathologists in many practice settings. Herein we demonstrate the utility of H&E morphology, immunohistochemistry, and MAML2 FISH in diagnosing OMEC in the setting of oncocytic salivary gland lesions. Future avenues, including tumor molecular profiling, will aid in elucidating clinicopathologic characteristics of this entity.
A Rare Case of Sinonasal Large Cell Neuroendocrine Carcinoma with Lymph Node Metastasis
Authors: Le P , Li S , Kovar J , Gonzalez Perez M
Published: October 2024

Introduction/Objective

Sinonasal carcinomas comprise less than 1% of cancers, and the most common types are squamous cell carcinoma at 51.6% and adenocarcinoma at 12.6%. There are only limited published reports of sinonasal large-cell neuroendocrine carcinoma (LCNEC). This entity has distinguishing immunohistochemical and histomorphologic features; it stains positively for neuroendocrine markers (i.e., synaptophysin and CD56) and histologically has abundant amphophilic cytoplasm with prominent nucleoli.

Methods/Case Report

We present a 60-year-old female patient who was evaluated for a submandibular neck lump. Computed tomography identified a 3.2 x 1.8 x 1.6 cm enhancing lesion with central necrosis in the right submandibular space, representing either an enlarged necrotic right submandibular lymph node or a neoplasm arising from the right submandibular gland. The pathology of the lymph node biopsy was consistent with metastatic high- grade neuroendocrine carcinoma. The neoplastic cells stained positively for INSM1, CK8/18, CK AE1/3 (subset), TTF- 1, and Ki-67 (50%).

Dotatate positron emission tomography showed evidence of focal activity in the right anterior nasal cavity supporting evidence with primary nasal cavity origin. Nasal endoscopy was performed, visualizing an area of necrotic friable tissue. Pathology confirmed the presence of large cell neuroendocrine carcinoma in the right nasal biopsies with metastatic LCNEC in right neck levels 1, 2A, 2B, 3, and 4. The malignant cells on hematoxylin and eosin stain had similar morphology to those in the initial lymph node biopsy, supporting a diagnosis of LCNEC.

Results (if a Case Study enter NA)

NA

Conclusion

Sinonasal large-cell neuroendocrine carcinomas are extremely rare. Upon literature search, there have been fewer than ten case reports published of this entity. Furthermore, large-cell neuroendocrine carcinoma behaves aggressively, and diagnosing this entity could result in earlier intervention and better patient outcomes. Highlighting the possibility of this diagnosis could broaden differentials in neoplasms that arise from the nose.
CRTC1::TRIM11-fusion tumor with rare sinonasal presentation and locally aggressive disease course
Authors: Bedeir A , Crymes A , Swanson M , Oberley M J , Evans M G
Published: October 2024

Introduction/Objective

Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT) is a rare dermatological neoplasm that has not yet been formally recognized by the World Health Organization. At present, our knowledge of this disease is limited to single reports and a series 41 cases with limited follow-up information. It is typically described as a skin lesion expressing melanocytic makers, often leading to its misdiagnosis as melanoma or clear cell sarcoma. CMTCT is regarded as an indolent tumor with infrequent recurrence after complete surgical excision. However, we present a case with uncommon sinonasal presentation and metastasis after multiple resections.

Methods/Case Report

A 23-year-old woman presented with a right nasal vestibule mass, requiring partial rhinectomy in a foreign country, where she subsequently received chemoradiation. Her tumor at the time was diagnosed as a mucosal melanoma. Eleven years following initial presentation, she demonstrated a recurrent right nasal tumor, as well as neck mass, cervical lymphadenopathy, and lung nodules. The patient then underwent a nasal endoscopic resection and modified neck dissection, which demonstrated a high-grade neoplasm with intersecting fascicles of medium-to-large monomorphic cells; whole exome and whole transcriptome sequencing performed on the resected neck mass identified a pathogenic TERT c.-146C>T alteration and CRTC1 exon 1::TRIM11 exon 2 fusion. The patient is currently alive and undergoing post-surgical chemoradiation.

Results (if a Case Study enter NA)

NA

Conclusion

This case expands our understanding of CMTCT and emphasizes its potentially aggressive behavior. The sinonasal presentation contrasts the tumor’s typical appearance on the skin and could mimic mucosal melanoma. Of note, our patient developed recurrent disease and distant metastases, thereby emphasizing the possible role of systemic therapy and suggesting that simple surgical excision may not be curative in all cases. Our case illustrates that CMTCT is an uncommon and potentially misidentified neoplasm, but that its proper diagnosis is essential for treatment selection and follow up.
Composite Lymphoma Comprising of BCL2 Rearrangement Negative, CD23 Positive Follicle Center Cell Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Case Report
Authors: Palathingal Bava E , liu W , Shen Y , Fang X , Carey J , Gomez-Gelvez J C , Inamdar K , Ghosh S
Published: October 2024

Introduction/Objective

BCL2 rearrangement negative, CD23-positive follicle center cell lymphoma (BCL2 neg CD23 pos FCL) is a rare, recently described provisional entity in International Consensus Classification (2022). It has a predominantly diffuse growth pattern and often involves inguinal region. The molecular profile includes a high frequency of STAT6 and CREBBP co-mutation as well as 1q gain and a recurrent 1p36 loss/TNFRS14 abnormalities. We describe a composite tumor comprising of a rare entity BCL2 neg CD23 pos FCL and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). To the best of our knowledge this is the first reported case description of this co-occurrence.

Methods/Case Report

A 59 y/o woman presented with right cervical and axillary lymphadenopathy (upto 1.6 cm). Sections showed partial effacement of nodal architecture by interfollicular and diffuse proliferation of atypical lymphoid cells. The interfollicular areas were comprised of a monotonous population of small lymphocytes.

Immunohistochemical stains performed showed that the interfollicular CD20+ PAX5+ atypical lymphoid cells coexpressed CD5, CD23, BCL2 and LEF1 and were negative for CD10, BCL6, CD3, and SOX11, with MIB1 of 5-10%. Based on these, a diagnosis of CLL/SLL was made.

Admixed with the CLL/SLL, a second neoplastic B-cell component that distorted nodal architecture was also identified. It composed of a diffuse proliferation of intermediate sized lymphoid cells with a centrocytic/centroblastic morphology. This smaller population of small to intermediate sized B cells expressed CD10, BCL6, and CD23 with a MIB1 proliferation index of ~30%. This population was CD5 and BCL2 negative. CD21 showed residual follicular dendritic cell meshworks. SOX11 and BCL1 were negative. Therefore, a diagnosis of BCL2 neg CD23 pos FCL was made.

Flow cytometry showed two distinct populations of monotypic B-cells, one CD5-positive and the other CD10-positive. FISH studies were negative for BCL2 and BCL6 rearrangements as well as del1p36. Cytogenetics was positive for trisomy 12, supporting CLL/SLL. Next Generation Sequencing showed Tier 1 / 2 mutations in STAT6, TNFRSF14, CREBBP, and FOXO1, supporting BCL2 neg CD23 pos FCL. Hence, this represents a unique case of composite CLL/SLL and BCL2 neg CD23 pos FCL. B cell gene rearrangement showed 2 distinct clones confirming 2 separate B cell lymphomas.

Results (if a Case Study enter NA)

NA

Conclusion

Here, we describe a composite CLL/SLL and BCL2 rearrangement negative, CD23 positive, FCL never previously described in literature.
Report of 3 Cases Diagnosed with Basal Cell Carcinoma and Systemic Mastocytosis with Favorable Prognosis
Authors: Zhou X , Shi C , Afolayan-Oloye O , Caponetti G
Published: October 2024

Introduction/Objective

The co-existence of basal cell carcinoma (BCC) and systemic mastocytosis is an exceptionally rare clinical occurrence, and the prognosis is not well-documented. Understanding the clinical and histopathological features of this uncommon association is relevant for accurate diagnosis, management, and prognostication.

Methods/Case Report

We conducted a retrospective analysis of three cases of BCC with concurrent systemic mastocytosis that were identified in the pathology database of the University of Pennsylvania from 2010 to 2023. Patient demographics, clinical and histopathologic characteristics, and treatment outcomes were reviewed.

Histopathologic assessment, immunohistochemistry, and C-KIT D816V mutation analysis (with an allele-specific PCR assay) were performed on biopsy material. Next-Generation Sequencing (NGS) was used to identify other hematologic neoplasm-associated mutations.

Results (if a Case Study enter NA)

All three cases were female with a median age of 55.3 years (50, 69, 47). In all three cases, atypical CD117+ tryptase+ CD25+ mast cells with mild to moderate pleomorphism were found in the dermis adjacent to the BCC cells. All three cases had bone marrow involvement. Serum tryptase levels were mildly elevated in all 3 patients (maximum 65.5 μg/L). All three cases harbor a C-KIT D816V mutation and a history of systemic glucocorticosteroids before the diagnosis of BCC. One of the cases was treated with phototherapy. NGS detected the following somatic mutations: Case #2 DNMT3A p.R882H c.2645G>A; Case #3 JAK2 V617F. Case #1 had multiple relapses of BCC, but a subsequent marrow biopsy did not identify any involvement by mastocytosis.

Case #2 had mast cell leukemia, which typically has a poor prognosis; however, this patient has survived for several years. Case #3 had essential thrombocythemia and systemic mastocytosis with an associated hematological neoplasm, and her symptoms were stable. Treatment modalities for the three patients ranged from surgical excision to anti-mastocytosis therapy, with favorable outcomes (Table 1).

Conclusion

The coexistence of BCC with mastocytosis poses diagnostic challenges due to its infrequency and varied clinical presentations. Previous literature reports on treatments of mastocytosis such as phototherapy and steroids, which have been identified as risk factors for the development of basal cell carcinoma. However, recognizing this unique combination in clinical practice may aid in providing appropriate treatment strategies, ultimately leading to favorable patient outcomes.
Isolated intracranial myeloid sarcoma as an acute myeloid leukemia relapse: A case report
Authors: Rivera D , Ibrahim N , Iashvili L , Christie-Nguyen P , mai B
Published: October 2024

Introduction/Objective

Adequate assessment during intraoperative consultation on a patient with a brain mass is imperative to provide critical information that will direct the therapeutic approach during surgery.

Methods/Case Report

The patient is a 67-year-old female with acute myeloid leukemia (AML) on maintenance therapy and in remission for the past 2 years that developed altered mental status and seizures. Imaging revealed a diffuse intra-axial mass within the corpus callosum and right hypothalamic region. A brain stereotactic biopsy was performed. Blood work showed mild leukopenia (3.63x109/L), thrombocytopenia (platelet count of 82x109/L), and an essential normal hemoglobin level of 11.9 g/dL. A frozen section assessment during intraoperative consultation revealed an infiltration of small blue cells, suggesting a hematolymphoid process. Further histological assessment showed small to intermediate-sized monomorphic cells in sheets and around the vessels with open fine chromatin, prominent nuclei, and scant cytoplasm admixed with tingible body macrophages. Differential diagnoses included high- grade B-cell lymphoma, Burkitt lymphoma, mantle cell lymphoma blastoid variant, lymphoblastic lymphoma, and myeloid sarcoma (MS). The tumor cells were positive for CD34, CD43, and MPO (subset) and negative for CD20, PAX5, TdT, CD3, and AE1/AE3 by immunohistochemical staining, consistent with MS. Concurrent bone marrow biopsy with flow cytometric evaluation showed progressive trilineage hematopoiesis without evidence of residual leukemia.

Results (if a Case Study enter NA)

NA

Conclusion

Intracranial MS is extremely rare, and literature reviews are limited to primarily case reports. MS can occur before, during, or after the initial presentation of AML. Interestingly, this patient had an isolated intracranial myeloid sarcoma as an AML relapse without bone marrow involvement. We aim to increase the awareness of isolated recurrence of AML in the form of an intracranial MS; this disease warrants consideration in patients with a history of a myeloid neoplasm who present with neurological symptoms despite the absence of peripheral disease.
A Rare Case of Diffuse Large B Cell Lymphoma Co-occurring with Small Lymphocytic Leukemia: De Novo Process or Richter’s Syndrome?
Authors: Li X , Saksena A , Devi P
Published: October 2024

Introduction/Objective

Diffuse large B-cell lymphoma (DLBCL) is the most prevalent subtype of lymphoma and can arise either de novo or through transformation from indolent lymphomas, such as Chronic Lymphocytic Leukemia (CLL), known as Richter syndrome (RS). DLBCL derived from RS tends to exhibit more aggressive behavior compared to de novo DLBCL.

Methods/Case Report

We present a case of a 57-year-old female with no significant medical history, who initially presented with antibiotic and prednisone-resistant sinusitis, progressing to bilateral neck pain and eye congestion. Computed tomography (CT) imaging revealed a 3 cm mass in the right nasal cavity extending to the right maxillary sinus and medial right orbit. Histopathological examination showed diffuse sheets of intermediate to large cells with irregular nuclear contours, dispersed chromatin, variably conspicuous nucleoli, and moderate cytoplasm. Additionally, scattered foci of monotonous, atypical lymphoid cells with lower grade morphology, including small size and condensed chromatin, were also present. Immunohistochemical analysis revealed differential staining patterns between the two cell populations. The larger atypical cells expressed CD20, PAX5, CD10, BCL-6, MUM1, BCL-2, MYC, CD19 (dim), and exhibited a high Ki-67 proliferation index (>80%). In contrast, the smaller atypical cells were positive for CD5, CD19, CD20, PAX5, BCL-2, and CD23 (subset), with a lower Ki-67 proliferation index (<5%). Flow cytometry analysis of tissue samples revealed two distinct clones: Surface Kappa-restricted CD19 dim B cells (38.9%) with CD5- CD10 dim CD20+ and surface Lambda-restricted CD19+ B cells (58.7%) with CD5+ CD10- CD20+. FISH analysis revealed no gene rearrangements. The final diagnosis was Diffuse large B-cell lymphoma, germinal center B- cell phenotype, with aggressive features and focal involvement by small lymphocytic lymphoma/chronic lymphocytic leukemia.

Results (if a Case Study enter NA)

NA

Conclusion

The relationship between the large B-cell lymphoma and SLL/CLL remains uncertain; however, given the different immunophenotype and light chain expression observed by flow cytometry, they are likely to represent separate processes.
UTILITY OF AUTOMATED HEMATOLOGY ANALYZER IN THE DETECTION OF MALIGNANT CELLS IN SEROUS EFFUSIONS
Authors: Sekaran A
Published: October 2024

Introduction/Objective

Although microscopic examination is the gold standard for body fluid malignant cytology, it has a higher turnaround time and inter observed variability. Screening of serous effusions for malignant cells using haematology methods of automated analysis provides a rapid and objective result to the clinicians for initiating necessary treatment.

Automated haematology analysers are equipped with body fluid (BF) mode that can detect high fluorescence cells body fluid (HF-BF) cells, mononuclear and polymorphonuclear (PMN) cells using flowcytometry laser scatter principles. The high fluorescence parameters useful for identifying malignant cells in the effusions

Methods/Case Report

The study was performed between February 2023to Februart 2024 at AIG Hospitals, Hyderabad after obtaining approval from the medical ethics committee of thehospital. Body fluidswere collected in K2 EDTA vaccutainer. Simultaneous preparation of smears for microscopic examination and morphometry wasdone and the smears were stained using Romanowsky stain (Leishmann & Giemsa).

Cytospin smears were prepared by cyto- centrifugation (Sakura cyto- tix). The slides were stained by Hematoxylin and eosin, May Grunwald Giemsa (MGG) and Papanicolaou (PAP) stains for morphological differentiation and detection of malignant cells. Cell blocks were prepared after through mixing of the fluid using direct sedimentation method and the slides were stained by haematoxylin and eosin stain. IHC was performed where ever necessary.

Results (if a Case Study enter NA)

A total of 258 fluid samples comprising of 223 ascitic and 35 pleural fluids. Medical statistical software version 20.2 was used for statistical analysisof the results. Considering fluid cell block analysis as the gold standard the patient population was divided into 2 groups, malignant (8 samples) and non- malignant cell group(250 samples). Cytological examination of cytospins smears has shown to have the highest specificity, PPV and NPV in the detection of malignant effusions.

Conclusion

Our study shows that cytology and histopathological examination of body fluids remains the gold standard for the detection of malignant cells. The HF-BF parameter acts as a rapid, useful tool to predict the presence of malignant cells in serous effusions and select samples for microscopic reviewing that would have otherwise gone undiagnosed. We believe that with defining cut off values for the HF-BF parameter may be used as an adjunct diagnostic tool.
Myeloid sarcoma mimicking as recurrent squamous cell carcinoma: What is the etiology?
Authors: Varghese I , Ahmed A A , mai B
Published: October 2024

Introduction/Objective

Myeloid sarcoma is an extramedullary malignancy of primitive myeloid cells and can occur during, preceding, or as a relapse of acute myeloid leukemia that occurs mostly in the soft tissue and skin.

Methods/Case Report

A 77-year-old white male with a history of oral squamous cell carcinoma status post resection (18 months ago) followed by radiation and chemotherapy (15 months prior), presented to the ear nose and throat clinic with increasing weakness and dizziness. He received two doses of Cisplatin and was currently on Pembrolizumab. On examination, there were two lesions in the oral cavity, one on the right gingivobuccal sulcus and a second on the left posterior mandibular ridge, suspicious for squamous cell carcinoma recurrence. Interestingly, the biopsy did not show evidence of recurrent squamous cell carcinoma but showed sheets of blasts that were positive for MPO, CD117, CD43, and CD68, consistent with myeloid sarcoma. Subsequent peripheral blood and bone marrow examinations showed acute myeloid leukemia.

Results (if a Case Study enter NA)

NA

Conclusion

Myeloid neoplasms post-cytotoxic therapy (MN-pCT) occur after radiation, alkylating agents, DNA topoisomerase II inhibitors, antimetabolites, and PARP1 inhibitors for a non-myeloid malignancy. Topoisomerase inhibitors are associated with MN-pCT after a latency period of 1 to 3 years; alkylating agents and radiation are associated with MN-pCT after a latency period of 5 to 7 years. Interestingly, this patient developed myeloid sarcoma in a previously irradiated area within 2 years. Cisplatin was discontinued after 2 doses due to side effect complications and is unlikely to be the culprit. Pembrolizumab is not considered to be a cytotoxic therapy and has not been reported to be associated with MN-pCT, however, the latency period for radiation-induced MN-pCT is unusually short in this patient and this raises the possibility of a Pembrolizumab-induced secondary myeloid neoplasm; additional investigation with other patients on this medication with second subsequent malignancies is required.
Nonimmune Hemolytic Anemia in Myelodysplastic Neoplasms (MDS) with U2AF1 Gene Mutation at S34 Hotspot: A Rare and Challenging Case Presentation
Authors: Li X , Krishnamurthy K , Sheikh F , Shi Y , Wang Y , Fang Y , Wang Q
Published: October 2024

Introduction/Objective

Hemolysis is recognized but not well understood in a subset of patients with myelodysplastic Neoplasms (MDS), largely through non-immune-mediated mechanisms. Lower survival rates are observed in MDS patients experiencing hemolysis. It is important to investigate the underlying mechanism including the molecular features of these cases. We hereby present a rare and challenging case of nonimmune hemolytic anemia in MDS with U2AF1 gene mutation at S34 hotspot.

Methods/Case Report

The patient is a 75-year-old male with past medical history of hypertension that presented with two weeks of 20 pounds weight loss, dyspnea on exertion and a syncopal event complicated with a parietal subarachnoid hemorrhage. Patient was found to have pancytopenia with severe anemia (hemoglobin 3.6 g/dl), reticulocytosis (reticulocyte 13.29%), decreased haptoglobin, while increased indirect bilirubin and lactate dehydrogenase. Spherocytes were detected in peripheral blood smear. With Coombs test being negative, all above are consistent with nonimmune hemolytic anemia. There is no evidence of paroxysmal nocturnal hemoglobinuria.

Bone marrow biopsy revealed trilineage hematopoiesis, many hypo-or mono-lobated dysplastic megakaryocytes and less than 5% blasts. Cytogenetics/FISH unveiled 5q deletion, 20q deletion and trisomy 8. Mutation in the U2AF1 gene at S34 hotpot is detected by next-generation sequencing. The overall findings are consistent with MDS with nonimmune mediated hemolysis.

Results (if a Case Study enter NA)

NA

Conclusion

Hemolysis, although uncommon in MDS, has a substantial impact on prognosis, treatment approaches and response. U2AF1 gene mutation is associated with poor outcomes in MDS patients. U2AF1 gene mutation at S34 hotpot is observed in 30% MDS patients with hemolysis in one recent report. Responses to erythropoiesis-stimulating agents and hypomethylating agents vary depending on different mutations, including U2AF1, SF3B1 and EZH2, with discrepancies across studies. Further investigation is warranted to elucidate the relationship between the molecular abnormalities and treatment response as well as prognosis in MDS patients with hemolysis.
Utility of Targeted Next Generation Sequencing (NGS) to Predict Hematologic Neoplasms with Germline Predisposition
Authors: Radova N , Miret E F , Gur H , Bizgarity P
Published: October 2024

Introduction/Objective

Hematologic neoplasms with germline predisposition are increasingly gaining clinical relevance as associated gene variants are emerging. These variants confer an increased risk for developing hematologic neoplasms as additional somatic aberrations accumulate. Recognition of germline predisposition is crucial to patient management as it would prompt genetic counseling and regular surveillance in affected patients and biological family members, as well as guide therapy, as many patients undergo allogeneic stem cell transplantation for which relatives are typically the preferred donors. Furthermore, these patients may respond differently to conventional therapies.

Clinical recognition of germline predisposition is challenging due to phenotypic heterogeneity and a lack of germline testing standards and resources. Next generation sequencing is routinely utilized to detect somatic variants associated with hematopoietic neoplasms. Molecular profiling may also potentially serve as a screening tool to suggest pathogenic germline variants.

Methods/Case Report

Comprehensive genomic profiling data was reviewed for 301 patients with known hematologic neoplasms. A somatic-germline-zygosity (SGZ) computational method classified variants by origin. Variants of unknown clinical significance were excluded. The final study showed 94 patients predicted to have germline variants. The variables analyzed include germline variants, concurrent mutations, diagnosis, sex, age, and ancestry.

Results (if a Case Study enter NA)

Acute myeloid leukemia was the most frequent diagnosis, followed by B-cell acute lymphoblastic leukemia, myeloproliferative neoplasms, myelodysplastic syndrome, and chronic myelomonocytic leukemia. The median patient age was 60 years, ranging from 6 months to 91 years. Male gender and European ancestry were proportionally greater. In this study, we identified 70 distinct genes with 145 germline pathogenic variants. The most common pathogenic germline variants were TET2, SRSF2, RUNX1, DNMT3A, and CHEK2.

Conclusion

In conclusion, SGZ computational methods can be used as a screening tool to predict possible germline mutations in hematologic malignancies, which will help guide treatment and improve patient and family outcomes
An unusual case of a de novo high-grade B cell neoplasm with MYC and BCL2 rearrangements, strong TdT expression, and BRAF V600E mutation
Authors: Asghar I A , Horwath M C , Zhang L , Abro B
Published: October 2024

Introduction/Objective

Aggressive de novo B cell neoplasms can rarely exhibit overlapping features of B- lymphoblastic leukemia/lymphoma (B-ALL) and high-grade B cell lymphoma (HGBL) making their definitive classification challenging. The distinction between mature and immature B cell neoplasms is critical as treatment approaches differ. We report a unique case of an aggressive B cell neoplasm that not only posed diagnostic difficulties but was also found to harbor a BRAF V600E mutation, an unusual finding in such cases.

Methods/Case Report

A 33-year-old man without any significant past medical history presented for evaluation of a large tonsil mass and diffuse lymphadenopathy. The tonsil was excised, and histologic examination showed a diffuse atypical infiltrate composed of medium to large monomorphic lymphoid cells with high-grade cytology. By immunohistochemistry, the atypical cells were positive for CD19, CD79a, CD22, PAX5, CD10 (strong), CD45 (strong), BCL2, MYC, and TdT (strong). Ki67 showed a high proliferation index (80%). The atypical cells were negative for CD20, CD34, CD1a, CD30, Cyclin D1, T cell markers, myeloid markers, HHV8, and EBER. Flow cytometry detected a CD10 positive B cell population that was negative for CD20, CD34, and surface light chain expression. Fluorescence in-situ hybridization (FISH) detected BCL2 and MYC rearrangements. Staging marrow showed diffuse involvement by a neoplastic infiltrate with similar features to those observed in the tonsil. Chromosome analysis showed a complex karyotype. The patient was treated with two cycles of da-EPOCH-R. A neck lymph node biopsy two months later showed persistent disease. Next-generation sequencing (NGS) on this sample demonstrated a BRAF V600E mutation at 31% allele frequency. A mutation-specific BRAF-VE1 immunostain was diffusely positive.

Results (if a Case Study enter NA)

NA

Conclusion

This was a diagnostically challenging case of a de novo B-cell lineage neoplasm with high-grade features, MYC and BCL2 rearrangements, and strong diffuse TdT expression. There is limited literature on mutational profiles and prognostic data for such cases, and whether they are best classified (and treated) as HGBL or B-ALL remains challenging and controversial. In our case, we also discovered an unexpected finding of a BRAF V600E mutation, which has not been reported in similar cases in the existing literature and could serve as a potential therapeutic target. Additional reporting and genetic profiling of such cases may help further elucidate their biology and guide treatment protocols.
Not All Therapy-Related Neoplasms are Myeloid: A Case Report of Rare B-ALL With t(5;14) Following Alkylating Agent Treatment
Authors: Patel R , Cortes P , Freeman J
Published: October 2024

Introduction/Objective

Most therapy-related hematologic neoplasms are myeloid (t-MN). Although not recognized as a distinct entity in the WHO classification of hematologic neoplasms, therapy-related acute lymphoblastic leukemia (t- ALL) cases have been previously reported. ALL incidence increases with any previous malignancy and is higher in those with previous treatment, supporting the concept of therapy-related ALL. B lymphoblastic leukemia/lymphoma (B- ALL) with t(5:14) is a rare subtype of the ALL (<1%) harboring a IL-3/IGH gene translocation. We present the first case of B-ALL with t(5;14) following treatment with alkylating agents for breast carcinoma.

Methods/Case Report

A 79-year-old female received docetaxel, carboplatin, trastuzumab, pertuzumab, Herceptin and radiotherapy for an invasive ductal breast carcinoma. Two years later, she developed progressive pancytopenia requiring a bone marrow biopsy.

Results (if a Case Study enter NA)

The bone marrow aspirate smears demonstrated B-ALL with 25% blasts, limited neutrophilic maturation, moderate erythroid dysplasia, and decreased megakaryocytes with occasional atypical forms. On the biopsy, atypical megakaryocytes and lymphoblasts were positive for TP53 immunohistochemical stain. On flow cytometry, blasts were positive for CD19, cCD79a, CD22, CD10, TdT, and HLA-DR and only 6% were positive for CD34. Next generation sequencing showed TP53 and NRAS mutation. Karyotyping revealed 46, XX, t (5;14) (q33; q13) and trisomy 21.

Conclusion

B-ALL with t (5;14); IGH/IL3 fusion has not been previously reported following treatment with alkylating agents. The presence of morphologic myeloid dysplasia developing after chemotherapy with alkylating agents support causality being therapy related rather than an independent process. The case expands the breadth of known therapy- related hematologic neoplasms and raises questions regarding the mechanisms of leukemogenesis.
Epstein Barr Virus Positive Mucocutaneous Ulcer versus Classic Hodgkin Lymphoma: Challenges in Diagnosis
Authors: Hamdan H , Chinchanikar S , Irfan A , Mateescu V , Lankachandra K
Published: October 2024

Introduction/Objective

Epstein- Barr virus positive mucocutaneous ulcer (EBVMCU) is a clinicopathologic entity first identified in 2010. It occurs in patients with immunosuppression and presents as a well circumscribed ulceration on the oropharyngeal mucosa, skin or gastrointestinal tract. Infiltrates of atypical lymphoid cells that may have appearances similar to Diffuse Large B-cell Lymphoma (DLBCL) or Classic Hodgkin Lymphoma (CHL) are seen.

Methods/Case Report

A 41 year old male patient with history of HIV infection presented with hematochezia and rectal pain, underwent sigmoidoscopy and a large ulcerated mass was present at the anal verge. Polymorphic infiltrates of small lymphoid cells, eosinophils, granulocytes, plasma cells, histiocytes and scattered large atypical lymphoid cells, morphologically mimicking Reed-Sternberg cells were identified. The large atypical lymphoid cells were positive for CD30, MUM-1, BCL-6, EBER (EBV) and negative for CD3, CD15, CD20, CD45, CD79a, SOX-10. Based on lack of B-symptoms, no lymphadenopathy, superficial lesions, reduced CD4/CD8 ratio and specific location, EBVMCU was favored. Eight months later, he presented with night sweats, decreased appetite and inguinal lymphadenopathy. Lymph node excision displayed infiltrates of predominantly small lymphocytes, histiocytes, plasma cells and eosinophils. Foci of scattered large atypical cells morphologically compatible with Hodgkin/Reed Sternberg cells with focal necrosis were noted. The atypical cells were positive for CD30, PAX5 (weak), CD20 (subset), CD15 (focal), MUM-1 and EBV-EBER. CHL, Mixed Cellularity Subtype was diagnosed.

Results (if a Case Study enter NA)

NA

Conclusion

As a newer entity, we don’t know if EBVMCU can co-exist with or progress to CHL/DLBCL. Therefore, EBVMCU patients should undergo vigilant screening.
Straightforward, Highly Useful, Innovative and Cost-Effective Method with Potential to Improve Personalized Diagnosis: Sectioning of Prostatectomy Specimen with a Single Blade
Authors: Gandhi S , Petersen J M , Jhala D
Published: October 2024

Introduction/Objective

There is potential for devices with an adjustable base and a single blade to precisely cut parallel slices of a prostatectomy specimen at a set preferred thickness to improve pathology practice by standardizing the tissue for histological review, allowing for precise punch biopsies of the slices for molecular diagnostics for biobanking and personalized therapy. The current standard method of sectioning the prostate involves serially sectioning the prostatectomy specimen by hand with a sharp long knife, leading to uneven sections.

Methods/Case Report

A device with an adjustable base was developed at a regional Veteran Affairs Medical Center (VAMC) that consists of two sets of multiple, vertically arranged parallel and flat bars measuring 10 cm in height, 1.5 cm in width and 0.3 cm in thickness spaced 0.4 cm from each other, resembling a comb with flat teeth. After inking, orientation, and removal of the seminal vesicles and apex and base margins, the prostatectomy specimen is immobilized between the two combs and sliced in parallel from apex to base to produce parallel consistent prostate slices. The ability to obtain punch biopsies from precise areas of the prostate was reviewed.

Results (if a Case Study enter NA)

The device results in uniform 4 mm thick oriented smooth specimen slices of good quality with minimal distortion. The device allows for the obtaining of punch biopsies taken at precise locations of the prostate corresponding to specific imaging locations (highly useful for biobanking or obtaining diagnostic tissue for molecular diagnostics for personalized therapy). The adjustable nature of the device and single blade gives the device flexibility in the specimen.

Conclusion

This device with an adjustable base and single blade allows for safe and precise parallel slicing. This is highly useful obtaining diagnostic standardized tissue, for obtaining biobank specimens and for obtaining material of precise location for molecular studies to guide the personalized therapy of tumors.