Peer-reviewed clinical pathology cases with anonymized clinical information, high-resolution histology images, differential diagnosis, expert discussion and references.
Over 800 peer-reviewed clinical pathology cases spanning all major subspecialties, curated by an international editorial board and updated weekly.
Each month our editorial board selects a single case of exceptional educational value. The case is presented in full diagnostic format with expert commentary, teaching points and references for continuing professional development.
A 34-year-old female presented with a slowly enlarging, painless mass on the medial aspect of the right thigh, first noticed approximately eight months prior to presentation. The patient had no significant past medical history, no prior surgical procedures in the affected limb and no family history of soft tissue tumours or hereditary cancer syndromes. Physical examination revealed a firm, non-tender, mobile subcutaneous mass measuring approximately 5 cm in greatest dimension, with no overlying skin changes and no regional lymphadenopathy.
MRI of the right thigh demonstrated a well-circumscribed, heterogeneously enhancing soft tissue mass measuring 5.2 × 3.8 × 3.4 cm, situated within the subcutaneous fat with no involvement of the underlying skeletal muscle or neurovascular bundle. The mass showed intermediate T1 signal intensity, heterogeneous high T2 signal with focal areas of low signal, and avid post-gadolinium enhancement. No perilesional oedema or satellite nodules were identified.
The clinical differential diagnosis included benign conditions such as desmoid-type fibromatosis and nodular fasciitis, as well as low-grade sarcomas such as dermatofibrosarcoma protuberans and low-grade myofibroblastic sarcoma. The lesion was excised with a planned marginal margin after multidisciplinary team discussion.
The specimen consisted of an ellipse of skin with attached subcutaneous tissue measuring 9.0 × 6.5 × 4.2 cm. The overlying skin was unremarkable. Serial sectioning revealed a well-circumscribed, ovoid, encapsulated mass measuring 5.3 × 3.7 × 3.5 cm, situated entirely within the subcutaneous adipose tissue. The cut surface was tan-white to grey-white, firm and lobulated, with focal areas of myxoid change and a single small area of haemorrhage measuring 0.8 cm. No necrosis was identified. The mass was separated from the deep surgical margin by 0.4 cm of adipose tissue, and from the closest peripheral margin by 1.2 cm.
Representative sections were submitted in a total of 14 cassettes, including the relationship of the tumour to the closest deep margin, peripheral margins and overlying skin.
Histological examination revealed a well-circumscribed, partially encapsulated neoplasm composed predominantly of spindle-shaped cells arranged in long, sweeping fascicles with a storiform-to-herringbone growth pattern. The tumour cells possessed elongated, tapering nuclei with finely dispersed chromatin, inconspicuous nucleoli and moderate amounts of palely eosinophilic cytoplasm. Nuclear pleomorphism was mild to moderate, with occasional hyperchromatic nuclei. Mitotic activity was low, estimated at 2–3 mitoses per 10 high-power fields (HPF), with no atypical mitotic figures identified.
Approximately 20% of the tumour showed a distinctly myxoid stromal background, with the spindle cells assuming a more stellate morphology and separated by abundant myxoid matrix. Curvilinear thin-walled blood vessels were conspicuous in these myxoid areas. Scattered throughout the lesion were clusters and small sheets of epithelioid cells with round nuclei, vesicular chromatin, small distinct nucleoli and abundant eosinophilic cytoplasm, comprising approximately 15% of the tumour volume.
A prominent perivascular inflammatory infiltrate was noted, composed of lymphocytes and occasional plasma cells. Focal haemosiderin deposition was present. No coagulative necrosis was identified. The tumour appeared completely excised, with the closest margin (deep) measuring 0.3 cm.
Special stains: Masson trichrome highlighted abundant collagen deposition within the fascicular areas. PAS with diastase was negative for intracytoplasmic glycogen. Reticulin stain demonstrated a delicate pericellular reticulin network around individual tumour cells.
An extensive immunohistochemistry panel was performed to elucidate the lineage of the neoplastic cells and to narrow the differential diagnosis. The following results were obtained:
| Marker | Result | Pattern / Comment |
|---|---|---|
| Vimentin | Positive (diffuse, strong) | Cytoplasmic; confirms mesenchymal differentiation |
| SMA (smooth muscle actin) | Positive (focal, moderate) | Cytoplasmic; approximately 30% of spindle cells |
| Desmin | Negative | No staining in tumour cells |
| h-Caldesmon | Negative | Argues against smooth muscle differentiation |
| S100 protein | Positive (focal, weak) | Nuclear and cytoplasmic; limited to epithelioid areas (~10%) |
| SOX10 | Negative | Argues against nerve sheath tumour |
| CD34 | Positive (patchy) | Membranous and cytoplasmic; approximately 40% of cells |
| EMA | Positive (focal, weak) | Membranous; scattered epithelioid cells only |
| AE1/AE3 (pan-cytokeratin) | Negative | No staining in tumour cells |
| ERG | Negative | Excludes vascular differentiation |
| STAT6 | Negative (nuclear) | Excludes solitary fibrous tumour |
| Beta-catenin | Negative (nuclear) | Membranous staining only; excludes desmoid fibromatosis |
| MDM2 | Negative | Excludes well-differentiated / dedifferentiated liposarcoma |
| CDK4 | Negative | Consistent with MDM2 result above |
| MUC4 | Negative | Excludes low-grade fibromyxoid sarcoma (see discussion) |
| Ki-67 | 8–10% | Low proliferation index overall; up to 15% in epithelioid foci |
Fluorescence in situ hybridisation (FISH) for MDM2 amplification was negative, excluding well-differentiated and dedifferentiated liposarcoma. FISH for FUS rearrangement was positive, identifying a FUS gene break-apart signal. Subsequent targeted RNA sequencing confirmed the presence of a FUS::CREB3L2 fusion transcript.
The differential diagnosis for a subcutaneous spindle cell neoplasm with myxoid areas and focal epithelioid morphology in a young adult female is broad and includes several entities of varying biological behaviour:
Low-Grade Fibromyxoid Sarcoma with Focal Epithelioid Morphology (Hybrid LGFMS/SEF Features)
Right thigh, excision — FUS::CREB3L2 fusion-positive. Margins clear (closest deep margin 0.3 cm).
The combination of a predominantly low-grade spindle cell morphology with alternating fibrous and myxoid zones, a focal epithelioid component (~15% of tumour volume), characteristic FUS::CREB3L2 fusion and the immunoprofile described above is consistent with low-grade fibromyxoid sarcoma demonstrating hybrid features with sclerosing epithelioid fibrosarcoma. This entity is now well recognised in the WHO Classification of Soft Tissue and Bone Tumours (5th edition, 2020) as part of the LGFMS/SEF spectrum.
Low-grade fibromyxoid sarcoma (LGFMS) is a distinctive soft tissue sarcoma first characterised by Evans in 1987. It typically affects young to middle-aged adults with a slight male predominance and most commonly arises in the deep soft tissues of the proximal extremities and trunk. Despite its deceptively bland histological appearance, LGFMS is a fully malignant neoplasm with a propensity for late local recurrence and distant metastasis, with reported metastatic rates of 5–18% in large series with long-term follow-up.
The relationship between LGFMS and sclerosing epithelioid fibrosarcoma (SEF) has been a subject of considerable interest and debate over the past decade. SEF, originally described by Meis-Kindblom and colleagues in 1995, was initially considered a separate entity characterised by nests and cords of monotonous epithelioid cells in a densely hyalinised stroma. However, accumulating evidence has demonstrated significant morphological, immunophenotypic and molecular overlap between these two entities, with shared FUS::CREB3L2 fusions identified in both tumour types. The 2020 WHO classification now recognises that LGFMS and SEF represent a morphological spectrum, with hybrid tumours showing features of both entities being well documented.
The current case exemplifies this spectrum. The predominant spindle cell morphology with alternating fibrous and myxoid zones is classic for LGFMS, while the focal epithelioid component with eosinophilic cytoplasm and rounded nuclei in a more sclerotic background represents the SEF end of the spectrum. Importantly, MUC4 immunohistochemistry, which is considered a highly sensitive and specific marker for LGFMS, was negative in this case. MUC4 negativity is reported in up to 10–15% of molecularly confirmed LGFMS cases and is more common in tumours with hybrid LGFMS/SEF features and in cases with FUS::CREB3L1 fusions rather than FUS::CREB3L2. This underscores the importance of molecular testing in establishing the diagnosis when the immunoprofile is ambiguous.
The management of LGFMS centres on complete surgical excision with clear margins. Wide local excision is the standard of care, with re-excision recommended for positive or close margins. The role of adjuvant radiotherapy remains controversial and is generally reserved for cases with positive margins where re-excision is not feasible. Given the well-documented propensity for late recurrence (reported up to 15–20 years after initial diagnosis), long-term clinical and imaging surveillance is essential. The presence of hybrid LGFMS/SEF features has been associated with a potentially more aggressive clinical course in some studies, further emphasising the need for vigilant follow-up in this patient.
LGFMS is a deceptively bland sarcoma. The low-grade cytology, low mitotic rate and well-circumscribed gross appearance can lead to under-diagnosis. Always consider LGFMS in the differential of a deep subcutaneous or intramuscular spindle cell neoplasm in a young adult, even when the histology appears benign.
LGFMS and SEF exist on a morphological spectrum. Hybrid tumours showing features of both are well documented and share the same characteristic FUS::CREB3L2 (or less commonly FUS::CREB3L1 or EWSR1::CREB3L1) gene fusions. Recognition of this spectrum is critical for accurate classification.
MUC4 is a useful but imperfect marker. While MUC4 immunohistochemistry is highly sensitive for LGFMS, negative cases exist (10–15%), particularly in hybrid LGFMS/SEF tumours. Molecular confirmation with FISH or next-generation sequencing for FUS rearrangements should be pursued in clinically and morphologically suspicious cases with negative MUC4.
Nuclear STAT6 and nuclear beta-catenin are essential exclusionary markers. Solitary fibrous tumour (STAT6-positive) and desmoid fibromatosis (beta-catenin nuclear-positive) are critical mimics that must be excluded by immunohistochemistry in the workup of any deep soft tissue spindle cell neoplasm.
Long-term follow-up is mandatory. LGFMS has a well-documented propensity for late recurrence and metastasis, with events reported up to 20 years after primary resection. Patients require lifelong surveillance with periodic clinical assessment and cross-sectional imaging.
Explore our curated collection of clinical pathology cases spanning all major subspecialties. Each case includes high-resolution images, IHC panels, expert discussion and referenced teaching points.
Showing 12 of 847 cases
A 47-year-old female presented with a 3.2 cm palpable mass in the upper outer quadrant of the left breast. Core needle biopsy revealed a high-grade invasive carcinoma that was negative for ER, PR and HER2 by immunohistochemistry. However, comprehensive genomic profiling using a 500-gene next-generation sequencing panel identified an unexpected NTRK3 fusion and high tumour mutational burden (TMB-H), prompting reconsideration of therapeutic strategy and enrolment in a basket trial with larotrectinib.
A 31-year-old male from southern India presented with chronic diarrhoea, weight loss and megaloblastic anaemia. Duodenal biopsies demonstrated subtotal villous atrophy with crypt hyperplasia and a mixed intraepithelial lymphocyte infiltrate. The distinction between coeliac disease and tropical sprue required careful clinical-pathological correlation, serology for tissue transglutaminase antibodies, HLA-DQ2/DQ8 typing and response to empirical antibiotic therapy.
A 62-year-old male presented with unexplained pancytopenia and massive splenomegaly without lymphadenopathy. Peripheral blood showed circulating lymphoid cells with villous projections but lacking the classic cytological features of hairy cell leukaemia. Bone marrow trephine biopsy revealed an interstitial and subtle sinusoidal infiltrate of medium-sized lymphoid cells. Flow cytometry demonstrated an unusual immunophenotype: CD19+, CD20+ (bright), CD11c+, CD103−, CD25−, CD123−, annexin A1−. BRAF V600E mutation testing was negative. The case illustrates the diagnostic challenges of hairy cell leukaemia variant (HCL-v), an entity with distinct biology and therapeutic implications compared to classical HCL.
A 19-year-old female presented with a rapidly growing, 1.1 cm amelanotic nodule on the left forearm, clinically suspected to be a pyogenic granuloma. Excision biopsy revealed a dome-shaped, asymmetric melanocytic proliferation with Kamino bodies, scattered mitoses including deep dermal mitotic figures, and focal pagetoid spread. The case illustrates the diagnostic challenges at the benign-malignant interface of Spitzoid melanocytic neoplasms, including the role of FISH, CGH and the recently developed MELTUMP prognostic algorithm. Sentinel lymph node biopsy findings and their uncertain prognostic significance in Spitzoid lesions are also discussed.
A 7-year-old boy presented with a four-week history of progressive headaches, vomiting and ataxia. MRI demonstrated a heterogeneously enhancing posterior fossa mass arising from the roof of the fourth ventricle with associated obstructive hydrocephalus. Intraoperative squash preparations and subsequent histological examination revealed a highly cellular embryonal neoplasm with nodular and internodular architecture. Methylation profiling classified the tumour as medulloblastoma, SHH-activated (TP53-wildtype), with important prognostic and therapeutic implications. The case discusses the current integrated molecular classification of medulloblastoma per the WHO CNS5 framework.
A 68-year-old male with a 30-year history of occupational asbestos exposure presented with progressive dyspnoea and a large right-sided pleural effusion. Cytological examination of the pleural fluid revealed a population of atypical mesothelial-like cells forming papillary clusters and acinar structures. The differential between epithelioid malignant mesothelioma and metastatic adenocarcinoma required an extensive cell block immunohistochemistry panel (calretinin, WT1, D2-40, CK5/6, BerEP4, MOC-31, TTF-1, claudin-4, BAP1 loss) and FISH for CDKN2A (p16) homozygous deletion. The importance of BAP1 loss by immunohistochemistry as a diagnostic adjunct for distinguishing reactive from neoplastic mesothelial proliferations is emphasised.
A 55-year-old female presented with rapidly progressive renal failure (creatinine rising from 95 to 612 µmol/L over three weeks), haematuria and proteinuria. Renal biopsy demonstrated severe crescentic glomerulonephritis affecting 18 of 22 glomeruli, with both cellular and fibrocellular crescents. Immunofluorescence showed pauci-immune pattern (no significant immunoglobulin or complement deposition). Serological testing revealed MPO-ANCA positivity at high titre with negative anti-GBM antibodies. The case discusses the differential diagnosis of crescentic GN, the importance of the ANCA serotype in predicting clinical phenotype and the current evidence for plasma exchange in severe ANCA-associated vasculitis based on the PEXIVAS trial results.
A 58-year-old non-smoking female with stage IV lung adenocarcinoma harbouring an EGFR exon 19 deletion (p.E746_A750del) developed disease progression after 14 months on first-line osimertinib. Tissue re-biopsy was technically challenging due to the location of the progressing lesion. Liquid biopsy (plasma cell-free DNA analysis) using a validated 74-gene panel identified the original EGFR exon 19 deletion alongside a novel EGFR C797S mutation in the cis configuration with the T790M resistance mutation, as well as MET amplification detected by copy number analysis. The case discusses mechanisms of acquired resistance to third-generation EGFR TKIs, the role of liquid biopsy in monitoring treatment response and resistance, and emerging therapeutic strategies for C797S-mediated resistance including fourth-generation EGFR inhibitors currently in clinical trials.
A 22-year-old male professional football player collapsed during training and could not be resuscitated despite immediate on-field cardiopulmonary resuscitation and defibrillation. Autopsy revealed a grossly enlarged heart (weight 485 g) with asymmetric septal hypertrophy. Histological examination demonstrated extensive myocyte disarray exceeding 20% of the septum, with interstitial and replacement fibrosis in a patchy distribution. Genetic testing on post-mortem blood identified a pathogenic variant in the MYH7 gene (c.1208G>A, p.R403Q). The case discusses the pathological features and molecular genetics of hypertrophic cardiomyopathy, the role of the forensic pathologist in sudden cardiac death investigation, the importance of molecular autopsy and the implications for cascade genetic screening of surviving family members.
A 45-year-old female on long-term anti-TNF therapy (adalimumab) for rheumatoid arthritis presented with persistently elevated liver enzymes (ALT 156 U/L, ALP 312 U/L, GGT 245 U/L) and low-grade pyrexia. Liver biopsy revealed well-formed, non-caseating epithelioid granulomas distributed predominantly in a portal and periportal pattern, with focal fibrin-ring granulomas and mild interface hepatitis. Special stains for acid-fast bacilli (Ziehl-Neelsen) and fungi (GMS, PAS) were negative, and PCR for Mycobacterium tuberculosis was negative on tissue. The case discusses the broad differential diagnosis of granulomatous hepatitis, the specific risk of granulomatous infections in immunosuppressed patients, the morphological features that help distinguish infectious from drug-induced aetiologies and the clinical decision-making regarding medication withdrawal.
A 48-year-old perimenopausal female with BMI 38 presented with heavy irregular menstrual bleeding unresponsive to medical management. Endometrial pipelle biopsy demonstrated architecturally crowded, cytologically altered glands exceeding 50% of the sampled area with loss of PTEN expression by immunohistochemistry. This teaching case reviews the evolution from the WHO94 hyperplasia classification to the current WHO/EIN (endometrial intraepithelial neoplasia) system, the diagnostic criteria for atypical endometrial hyperplasia / EIN, the role of PTEN, PAX2 and mismatch repair immunohistochemistry, and the clinical management pathway including the indications for hysterectomy versus conservative hormonal management.
A 56-year-old female presented with persistent cough, low-grade fever and bilateral patchy consolidation on chest CT that migrated over serial imaging. Video-assisted thoracoscopic lung biopsy demonstrated the classic histological pattern of organising pneumonia with Masson bodies (intraluminal plugs of granulation tissue) within alveolar ducts and alveoli, with preservation of the underlying lung architecture. This trainee-level case provides a systematic approach to the differential diagnosis of the organising pneumonia pattern, distinguishing cryptogenic organising pneumonia (COP) from secondary causes including drug-induced lung injury, connective tissue disease, infection and the organising phase of diffuse alveolar damage.
Our clinical cases are designed as structured educational resources for pathologists at every career stage. Each case is aligned with established CPD and CME frameworks to support lifelong learning and professional accreditation.
Our trainee-level cases are mapped to the FRCPath, ABPath and RCPA curricula, covering the core diagnostic patterns and systematic approaches expected at board level. Each case includes structured learning objectives, a stepwise diagnostic algorithm and self-assessment questions with referenced model answers.
Each clinical case published by Global Pathology Publications is accredited for continuing professional development by the Royal College of Pathologists (UK) and recognised by the Accreditation Council for Continuing Medical Education (ACCME) for AMA PRA Category 1 Credits. Pathologists may claim up to 2.5 CPD credits per completed case.
Clinical cases from our library are widely used by pathology departments for multidisciplinary team meetings, slide seminars, journal clubs and quality assurance exercises. Institutional subscribers receive access to our full case archive including downloadable presentation-ready slide sets and structured discussion guides.
We welcome clinical case submissions from pathologists, trainees and researchers worldwide. Every submission undergoes rigorous peer review by subspecialty experts before publication.
Compile the clinical history, gross and microscopic descriptions, IHC/molecular results, differential diagnosis, final diagnosis and discussion. Ensure all patient information is fully anonymised. Obtain documented patient consent or institutional ethics approval for publication.
Submit high-resolution histology images (minimum 300 dpi, TIFF or PNG format) with appropriate labelling. Include all relevant special stain and IHC images. Whole slide images in SVS, NDPI or MRXS format are encouraged and will be hosted on our digital pathology viewer.
Each submission is reviewed by a minimum of two subspecialty-qualified pathologists from our international editorial board. Reviewers assess diagnostic accuracy, educational value, image quality and manuscript clarity. The average review turnaround is 3–4 weeks.
Accepted cases are published with full author attribution, institutional affiliation and DOI assignment. Authors receive a certificate of publication and CPD credit for the educational contribution. Published cases are indexed in Google Scholar.