Important Diagnostic Pitfall Research Articles

"Aberrant" expression of skeletal muscle markers in neuroendocrine carcinomas: a significant diagnostic pitfall.

In this study, we investigate the expression of muscle markers, including the specific skeletal muscle markers myogenin and myoD1, in neuroendocrine carcinomas (NECs). The study included 23 NECs from various sites (14 small cell NECs and 9 large cell NECs). These were stained with desmin, myogenin and myoD1. Positive staining with at least one muscle marker was observed in 14 cases (61%). 8 (35%), 8 (35%) and 11 (48%) of the cases were positive with desmin, myogenin and myoD1 respectively. In most, but not all, cases positive staining was focal generally involving < 10% of tumour cells. Expression of muscle markers is not uncommon in NECs. This represents an important diagnostic pitfall of which pathologists should be aware. In reporting this phenomenon, we speculate on the pathogenesis of this "aberrant" expression of muscle markers.

Fumarate Hydratase-Deficient Renal Cell Carcinoma with Nucleolar Pattern of GATA3 Immunoexpression: Report of 2 Cases.

Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare aggressive type of renal cell carcinoma. The significant morphologic overlap with other types of renal neoplasia and the limited availability of FH and 2-succinylcholine immunostains for diagnostic use outside large referral centers have created numerous diagnostic pitfalls. As FH-deficient RCC can be associated with hereditary leiomyomatosis and renal cell cancer syndrome, the importance of an accurate diagnosis goes beyond the prognosis and treatment of an individual patient. We present 2 patients with FH-deficient RCC showing a peculiar pattern of GATA3 immunoexpression restricted to tumor nucleoli. If confirmed in further larger studies, this could provide an additional diagnostic clue for considering the FH-deficient RCC diagnosis, and given the frequent papillary morphology and possible hilar location can lead to the misdiagnosis as high-grade urothelial carcinoma, and is an important diagnostic pitfall to be aware of.

De-differentiated liposarcomas with solitary fibrous tumour-like pattern and STAT6 nuclear expression: an important diagnostic pitfall.

De-differentiated liposarcomas with solitary fibrous tumour-like pattern and STAT6 nuclear expression: an important diagnostic pitfall.

The utility of fluorescence in situ hybridization (FISH) in determining DNA damage-inducible transcript 3 (DDIT3) amplification in dedifferentiated liposarcomas – an important diagnostic pitfall

Background and objectiveDedifferentiated liposarcoma (DDLPS) is characterized by non-lipogenic sarcoma fields coexisting with adipocyte-rich well-differentiated areas. Amplification of the 12q13–15 region includes the MDM2 and DDIT3 genes. MDM2 amplification is considered a genetic hallmark of DDLPS, while DDIT3 is typically rearranged in myxoid liposarcoma. Recent studies showed that DDIT3 amplification is associated with myxoid liposarcoma-like (LPS-like) morphology in DDLPS. Our study aimed to evaluate the status of MDM2 and DDIT3 by FISH in DDLPS and correlate it with MLPS-like features. Material and methodsSix patients with MLPS-like morphology DDLPS were investigated pathologically, immunohistochemically, and genetically. The control groups of patients with classical DDLPS morphology and well-differentiated liposarcoma (WDLPS) were established and molecularly assessed as well. Fluorescence in situ hybridization (FISH) used in routine diagnostics was performed to determine the status of MDM2 and DDIT3 genes. ResultsThe patient's mean age was 64 (range from 43 to 85 years) with a 5:4 male to female ratio. Tumors were localized retroperitoneally (15) and extra-retroperitoneally (3). All cases demonstrated amplification of the 12q15 region containing MDM2 gene and co-amplification of the 5′ DDIT3 FISH Probe representing DDIT3 telomeric tag. However, we did not find the relation of myxoid LPS-like morphology with DDIT3 amplification as previously reported. ConclusionsThe biopsy material from DDLPS with myxoid areas can be misclassified as myxoid liposarcoma. Indeed, according to the histological image, DDIT3 status may be evaluated first. In these cases, we show that the DDIT3 telomeric tag amplification assessed by FISH, is a common, nonspecific feature, which is also found in classical DDLPS and WDLPS. Therefore, we believe that co-amplification of DDIT3 and MDM2 may be considered a spectrum of the 12q13–15 region amplification due to the specification of FISH methodology.

Clinicopathologic and Genomic Characterization of Inflammatory Myofibroblastic Tumors of the Head and Neck: Highlighting a Novel Fusion and Potential Diagnostic Pitfall.

Inflammatory myofibroblastic tumor (IMT) is a distinctive fibroblastic and myofibroblastic spindle cell neoplasm with an accompanying inflammatory cell infiltrate and frequent receptor tyrosine kinase activation at the molecular level. The tumor may recur and rarely metastasizes. IMT is rare in the head and neck region, and limited information is available about its clinicopathologic and molecular characteristics in these subsites. Therefore, we analyzed a cohort of head and neck IMTs through a multi-institutional approach. Fourteen cases were included in the provisional cohort, but 1 was excluded after molecular analysis prompted reclassification. Patients in the final cohort included 7 males and 6 females, with a mean age of 26.5 years. Tumors were located in the larynx (n=7), oral cavity (n=3), pharynx (n=2), and mastoid (n=1). Histologically, all tumors showed neoplastic spindle cells in storiform to fascicular patterns with associated chronic inflammation, but the morphologic spectrum was wide, as is characteristic of IMT in other sites. An underlying fusion gene event was identified in 92% (n=11/12) of cases and an additional case was ALK-positive by IHC but could not be evaluated molecularly. ALK represented the driver in all but 1 case. Rearrangement of ALK, fused with the TIMP3 gene (n=6) was most commonly detected, followed by 1 case each of the following fusion gene partnerships: TPM3-ALK, KIF5B-ALK, CARS-ALK, THBS1-ALK, and a novel alteration, SLC12A2-ROS1. The excluded case was reclassified as spindle cell rhabdomyosarcoma after detection of a FUS-TFCP2 rearrangement and retrospective immunohistochemical confirmation of rhabdomyoblastic differentiation, illustrating an important diagnostic pitfall. Two IMT patients received targeted therapy with crizotinib, with a demonstrated radiographic response. One tumor recurred but none metastasized. These results add to the growing body of evidence that kinase fusions can be identified in the majority of IMTs and that molecular analysis can lead to increased diagnostic accuracy and broadened therapeutic options for patients.

Expression of germinal center cell markers by extranodal marginal zone lymphomas of MALT type within colonized follicles, a diagnostic pitfall with follicular lymphoma

We reviewed 341 consecutive cases of marginal zone lymphoma (MZL) (47) or follicular lymphoma (FL) (294) of which 7 were difficult to distinguish due to perceived coexpression of BCL6 and BCL2 by tumor cells in follicular foci. This stimulated us to develop dual BCL6/BCL2 immunohistochemistry, allowing us to assess coexpression among individual cells. Dual staining confirmed coexpression in 6 of 7 cases, all extranodal MZL (ENMZL) based on overall features and representing 13% of MZL in this series. These findings confirm that MZL cells have plasticity regarding protein expression within the germinal center (GC) microenvironment, an important diagnostic pitfall. Intriguingly, in all MZL expressing BCL6, non-neoplastic GC B cells within colonized follicles showed diminished or absent CD10 expression but preserved BCL6 and high ki67. This finding suggests plasticity of CD10 expression in non-neoplastic GC B cells in the context of colonization by MZL, possibly related to NF-kB dysregulation.

Biopsies of hepatocellular carcinoma with no reticulin loss: an important diagnostic pitfall

The reticulin stain is a critical diagnostic aide used to differentiate benign hepatocellular proliferations from well differentiated hepatocellular carcinoma (HCC). Rarely, however, hepatocellular carcinomas do not show definitive loss of reticulin in liver biopsy specimens. To study this group of tumors, 11 HCC with no reticulin loss in 10 patients were collected and studied. Analysis of demographics showed a typical enrichment for men with a typical age for HCC presentation of 69±7 years for adults. The background livers showed advanced fibrosis or cirrhosis in 6 of 6 cases with available information. The tumors were all well differentiated. Cytological atypia was mild and consisted of very mild nuclear atypia (8 cases), mild increase in N:C ratio (3 cases), and pseudorosette formation (4 cases). The cytological/architectural atypia was insufficient in isolation to diagnose HCC. Additional studies, however, showed an increased Ki-67 proliferative rate (N=10/10 stained cases). The Ki-67 proliferative rate was estimated to be between 5 and 10% in all tested cases and was clearly increased from adjacent liver at low power. Glypican 3 positivity (4 tumors) and alpha fetoprotein (AFP) (1/8 stained cases) positivity also helped make the diagnosis of HCC. Morphologically, the HCC had conventional morphology with five showing steatosis/steatohepatitic features and one showing intratumoral fibrosis. A control group of macroregenerative/dysplastic nodules showed no increase in Ki-67 proliferation and no staining for glypican 3. These findings highlight an important diagnostic pitfall: rare HCC show no reticulin loss on biopsy. In these challenging cases, additional findings are useful to make a diagnosis of HCC: increased Ki-67 and positive staining for aberrant expression of proteins such as glypican 3 or AFP.

Hepatocellular carcinomas can be Special AT-rich sequence-binding protein 2 positive: an important diagnostic pitfall

Special AT-rich sequence-binding protein 2 (SATB2) is a sensitive and specific marker for tumors originating with the colon and appendix. It is now commonly used in surgical pathology, while working up carcinomas of unknown primary. We had anecdotally encountered occasional hepatocellular carcinomas (HCCs) that were SATB2 positive. Immunohistochemical expression of SATB2 in HCChas not yet been examined in detail. In this study, we evaluated SATB2 expression in 46 HCCs. Nineteen (41%) of 46 HCCs were positive for SATB2. SATB2 expression in HCCs was more commonly seen in poorly differentiated tumors (11 of 13 cases, 85%) than well and moderately differentiated tumors (8 of 33 cases, 24%), p value=0.0001. No other statistically significant correlations were observed (p>0.05). There were no other statistically significant correlations between SATB2 expression and age, gender, background liver disease, and cirrhosis (p>0.05). Results of our study show that a significant subset (41%) of HCCs can be SATB2 positive. Awareness of this phenomenon is important as SATB2 expression in a liver tumor does not completely exclude a diagnosis of HCC.

Pseudocarcinomatous Squamous Hyperplasia Involving Bone: A Diagnostic Pitfall Mimicking Squamous Cell Carcinoma.

Pseudocarcinomatous squamous hyperplasia (PSH) within the bone is uncommon and closely mimics well-differentiated squamous cell carcinoma (SCC). It arises from cutaneous or mucosal surfaces and grows directly into the bone. This study analyzes a large series of PSH and discusses the clinicopathologic features that facilitate its distinction from SCC. Cases were identified from the surgical pathology files between 1985 and 2020. The 31 cases included 21 males, 9 females, 1 unknown sex; who were 20 to 87 years old (average: 59 y). Sites included mandible-17, maxilla-5, toes-4, and 1 case from finger, femur, tibia, ischium, and unknown. Fourteen patients had a history of SCC, 13 treated with resection and chemoradiation and developed infected osteoradionecrosis, 4-medication-related osteonecrosis, 3-peripheral vascular disease, and diabetes mellitus, 3-trauma, 3-osteomyelitis, 3-unknown, and 1-hematologic malignancy. All cases exhibited severe osteomyelitis and nests of reactive keratinizing squamous epithelium that matured towards the bone surface, lacked significant atypia, or mitotic activity but permeated the medullary cavity. Patients with previous SCC developed PSH after 2 months to 8 years (average: 4 y). Nineteen of 30 patients had follow-up (2 to 48 mo, average: 17 mo); 6 patients experienced repeated debridements over 2 months to 1 year; no patient developed SCC. PSH involving bone is infrequent, complicates severe osteomyelitis, and is often therapy related. The clinical findings are usually not concerning for malignancy, however, the histologic findings are an important diagnostic pitfall because they mimic SCC.

Microglandular Adenosis and Associated Invasive Carcinoma.

Microglandular adenosis is a rare borderline neoplastic lesion of the breast composed of haphazardly located small, round tubules with a single cell layer interspersed within breast stroma and/or adipose tissue. Microglandular adenosis is devoid of a myoepithelial cell layer, and has a characteristic immunophenotype, being positive for S100 and negative for estrogen receptor, progesterone receptor, and HER2/neu. When associated with cancer, microglandular adenosis and associated invasive carcinoma share the same molecular alterations, including TP53 mutation; therefore, microglandular adenosis is considered a nonobligate precursor of triple (HER2/neu, estrogen and progesterone receptors)-negative breast carcinoma. Microglandular adenosis is an important diagnostic pitfall as it can be easily mistaken for a low-grade invasive carcinoma. To provide a review of the clinicopathologic features of microglandular adenosis and associated invasive carcinoma, with emphasis on key features separating entities in the differential diagnosis. Review of current literature on microglandular adenosis and associated invasive carcinoma and personal experience of authors. Microglandular adenosis can mimic breast carcinoma; attention to key features, including morphologic-immunophenotypic correlation, is essential in establishing the diagnosis.

Sclerosing Pneumocytoma: A Ten-Year Experience at a Western Balkan University Hospital.

Background and objective: Sclerosing pneumocytoma is a rare, benign tumor of the lung that represents a diagnostic challenge due to the diversity of pathohistological findings. The aim of this study was to present a 10-year experience with sclerosing pneumocytoma of a large center for the diagnosis and treatment of pulmonary diseases, and to emphasize differential diagnostic dilemmas as a potential source of errors. Material and Methods: This represents a retrospective study of six patients diagnosed and treated with sclerosing pneumocytoma in the 10-year period. The study analyzed various parameters, which are: Sex, age, symptoms, size and localization of the tumor, and its gross and histological features. Results: Sclerosing pneumocytoma was more frequently diagnosed in females (83.34%). The patients ranged in age from 38 to 61. Most of the patients (66.66%) were asymptomatic. Two patients underwent a video-assisted thoracoscopic surgery, two patients had a video-assisted minithoracotomy, and two patients underwent a thoracotomy in order to remove the tumor. The tumor was localized in the left lower lobe, in the right upper lobe, and in the right lower lobe in 50%, 33.34%, and 16.66% of patients, respectively. The tumor size ranged from 1 to 2.5 cm. A pathohistological examination of all six cases reported that all four major histological patterns were found in tissue sections: solid, papillary, sclerosing, and hemorrhagic. In all six cases, an immunohistochemical analysis showed positive expression of TTF-1 and panCK in surface epithelial cells, and TTF-1 positivity and panCK negativity in round stromal cells. Conclusions: Sclerosing pneumocytoma is a strictly histological diagnosis supported by clinical and radiological findings and corresponding immunohistochemical methods. Lung pathologists should always keep this tumor in mind, since its spectrum of differential diagnosis is wide, and therefore it can be an important diagnostic pitfall.

Cutaneous epithelioid angiomatous nodule: a report of a series including a case with moderate cytologic atypia and immunosuppression

BackgroundCutaneous epithelioid angiomatous nodule (CEAN) is a very rare and relatively recently recognized vascular proliferation characterized usually by minimal cytological atypia and accompanying mitotic activity. As such, CEAN represents an important diagnostic pitfall, which could lead to significant misdiagnosis and unnecessary treatment.MethodsThe clinicopathologic findings of 5 cases of CEAN were reviewed including a unique case with typical findings but also moderate cytologic atypia and brisk mitotic activity in a patient on immunosuppression.ResultsThe cases were in 3 women and 2 men ranging in age from 18 to 61 years with lesions in the neck (2 cases), upper arm, back and shoulder. In 4 of the cases, the patients did not have any relevant potentially contributory clinical history, and in 1 case the patient was on immunosuppressive treatment. All 5 cases were superficially located within the dermis, well-circumscribed and similarly composed of epithelioid cells displaying minimal (in 4 cases) and moderate (1 case) atypia. The mitotic count ranged from 1 to 3 per 10 high power fields (HPF) in 4 cases and up to 9 per 10 HPF in the immunosuppressed patient. Atypical mitoses were not encountered in any of the cases. Two lesions that were incompletely excised recurred, but none of the patients showed distant metastases.ConclusionWhile cytologically alarming, CEAN has a characteristic microscopic appearance and if completely excised follows an indolent course.

Sinonasal tumors : News from the WHO with special reference to mesenchymal entities

The last two decades have seen significant advances in the pathology of sinonasal tract neoplasms. This was the consequence of the availability of several innovative diagnostic tools, which resulted in adynamic evolution of entities and splitting of newly defined or conceptualized entities and subtypes that have been included in the spectrum of old heterogeneous diseases. Most of these new tumor subtypes have distinctive demographic, clinicopathologic, and biological characteristics with prognostic and therapeutic implications for individual patients. NUT carcinoma (NUT midline carcinoma) was separated from the spectrum of sinonasal undifferentiated carcinoma (SNUC) and is defined by specific recurrent translocation. On the other hand, the recently described SMARCB1-deficient carcinoma (while probably representing adistinctive clinicopathologic entity) remained as avariant in the SNUC spectrum. Anew neoplasm in the spectrum of non-keratinizing carcinomas is the human papillomavirus(HPV)-related adenoid-cystic-like sinonasal carcinoma with its distinctive, albeit diverse, morphology. In the group of small round-cell malignancies, adamantinoma-like Ewing sarcoma has been delineated as an important diagnostic pitfall given its prominent epithelial differentiation. Inclusion of the biphenotypic (myoneural) sinonasal sarcoma (BSS) as alow-grade malignancy defined by recurrent PAX3/MAML3-translocation represents an important feature of the new WHO classification given the distinctive biological behavior of this low-grade non-metastasizing rare entity, which has been uniformly misclassified as a peripheral nerve sheath tumor or leiomyosarcoma in the past. Recognition of CTNNB1 mutations and STAT6/NAB2 gene fusions as defining genetic markers for sinonasal hemangio‑/glomangiopericytoma and solitary fibrous tumors, respectively, represents another important achievement in recent years. This review summarizes the new aspects in the WHO classification and also addresses recently described entities that have not been included in the WHO classification.

Sentinel case of Richter transformation from chronic lymphocytic leukaemia/small lymphocytic lymphoma to CD3+ diffuse large B-cell lymphoma

AimTo report the first case of a Richter syndrome where small lymphocytic lymphoma (SLL) progressed to a CD3+ diffuse large B-cell lymphoma (DLBCL).MethodsMacrodissection of small and large cell lymphomatous components...

Reed-Sternberg-Like Cells in Non-Hodgkin Lymphomas.

Large atypical cells with morphologic and immunophenotypic features resembling Reed-Sternberg cells can be seen in the background of reactive lymphadenopathies as well as non-Hodgkin lymphomas. The presence of these cells is an important diagnostic pitfall that must be recognized by pathologists who regularly interpret lymph node biopsies. A thorough evaluation of the morphologic and immunophenotypic features of these cells and the cellular milieu is crucial in achieving the correct diagnosis. In this review, examples of lymphomas presenting with Reed-Sternberg-like cells will be provided. Additionally, a detailed description of the common morphologic and immunophenotypic features of these cells, as well as strategies that can be used to distinguish them from the Reed-Sternberg cells of classical Hodgkin lymphoma, will be emphasized.

Biopsy diagnoses of clinically atypical pigmented lesions of the head and neck in adults.

A subset of facial melanoma in situ has histological features that overlap with those of "dysplastic" nevi. The authors evaluated this important diagnostic pitfall by assessing the frequency of melanoma as the final diagnosis in skin biopsies submitted over a 1-year period with a clinical impression of "atypical" or dysplastic nevus from the head or neck of adults. A total of 1998 biopsies met inclusion criteria. Final diagnoses included both melanocytic and nonmelanocytic processes. Clear trends were noted based on the age of the patient with benign nevi encompassing nearly 70% of specimens in patients aged 21-29 years and <10% in patients aged 70 years and above. The incidence of atypical nevi decreased with age (16% in 21-29 years, 3% in age 70+ years). Nineteen of the 180 (10%) atypical nevi in our series were located on the face (7, cheek; 6, forehead; 3, jawline; and 3, temple), a location not traditionally associated with atypical nevi. Facial atypical nevi were found in all age groups. Malignant melanoma accounted for 1.8% of all specimens increasing from 0% in the patients aged 21-29 years to 5% in patients aged 70 years and above. Caution is warranted when evaluating skin biopsies from sun-damaged skin of the head or neck of an older adult submitted with a clinical diagnosis of atypical nevus. However, the authors' findings suggest that atypical nevi with histological features of dysplastic nevi occur on the head and neck of adults, including elderly adults. The incidence of such lesions decreases with age as the incidence of melanoma increases, and careful clinicopathologic correlation is vital.

Diagnostic pitfalls of differentiating desmoplastic small round cell tumor (DSRCT) from Wilms tumor (WT): overlapping morphologic and immunohistochemical features.

Desmoplastic small round cell tumor (DSRCT) and blastemal-predominant Wilms tumor (WT) share overlapping histologic features, yet accurate distinction is critical because of differing prognosis and treatment. We encountered a neck mass in a young adult with a concomitant abdominal mass. The neck mass was initially concerning for DSRCT on the basis of the poorly differentiated morphology, desmoplastic stroma, and immunoreactivity for desmin and cytokeratin. However, focal triphasic elements and glomeruloid bodies were identified on deeper sections, WT1 immunoreactivity was seen with antibodies to both the amino-terminus and carboxy-terminus, and EWSR1-WT1 rearrangement studies were negative, supporting the ultimate diagnosis of WT. On the basis of the overlapping histologic features of DSRCT and blastemal-predominant WT, we undertook a comparison study of desmin and cytokeratin reactivity patterns. We found that, whereas desmin reactivity was more frequent in DSRCT (11 of 12) than in WT blastema (11 of 22, P=0.024), dot-like perinuclear reactivity was seen with equal frequency in desmin-reactive DSRCT (10 of 11) and WT blastema (10 of 11), illustrating an important diagnostic pitfall. Moreover, we demonstrate coexpression of desmin and cytokeratin in both DSRCT (9 of 12) and WT blastema (11 of 22). Importantly, although dot-like desmin reactivity and coexpression of desmin and cytokeratin are historically associated with DSRCT, we demonstrate that these features can be seen in either DSRCT or blastemal-predominant WT. In these challenging cases, detection of an EWSR1-WT1 rearrangement and selective WT1 carboxy-terminus immunoreactivity (characteristic of DSRCT) or dual immunoreactivity for the WT1 amino-terminus and carboxy-terminus (characteristic of WT) remain the most discriminating diagnostic tools.

Thymoma with loss of keratin expression (and giant cells): a potential diagnostic pitfall.

Due to its profound therapeutic consequences, the distinction between thymoma and T-lymphoblastic lymphoma in needle biopsies is one of the most challenging in mediastinal pathology. One essential diagnostic criterion favouring thymoma is the demonstration of increased numbers of keratin-positive epithelial cells by immunohistochemistry. Loss of keratin expression in neoplastic epithelial cells could lead to detrimental misdiagnoses. We here describe a series of 14 thymic epithelial tumours (11 type B2 and B3 thymomas, 3 thymic carcinomas) with loss of expression of one or more keratins. Cases were analysed for expression of various keratins and desmosomal proteins by immunohistochemistry and immunofluorescence and compared with 45 unselected type B thymomas and 24 thymic carcinomas arranged in a multitissue histological array. All 14 cases showed highly reduced expression of at least one keratin, three cases were completely negative for all keratins studied. Of the 14 cases, 13 showed strong nuclear expression of p63. Expression of desmosomal proteins was preserved, suggesting intact cell contact structures. Loss of expression of broad-spectrum-keratins and K19 was observed in 3 and 5 % of unselected thymomas and in 30 and 60 % of thymic carcinomas. A proportion of keratin-depleted thymomas contained giant cells, reminiscent of thymic nurse cells. Loss of keratin expression in type B2 and B3 thymomas is an important diagnostic pitfall in the differential diagnosis with T-lymphoblastic lymphoma and can be expected in 5 % of cases. A panel of epithelial markers including p63 is warranted to ensure correct diagnosis of keratin-negative mediastinal tumours.

Bizarre Stromal Cells in the Esophagus

Esophageal bizarre stromal cells (BSCs) represent an important diagnostic pitfall, since they can closely resemble a malignancy, thus leading to a significant overtreatment. We recently encountered a case in a healthy 38-year-old man, with a normal blood count, who underwent an upper gastrointestinal endoscopy during the follow-up of a grade I esophagitis and hiatus hernia. The endoscopy revealed an ulcerated sessile polyp that, on histology, consisted of a proliferation of round atypical discohesive cells, with a variable amount of cytoplasm, large nuclei, and prominent eosinophilic nucleoli. They were intermingled with many granulocytes and plump vessels, in a background of granulation tissue. Immunohistochemical stains with pan-cytokeratin, S100, and CD31 were negative and Ki67 stained only very few nuclei. At variance with other anatomical sites and despite the putative fibroblastic or myofibroblastic origin, BSCs in esophagus can have a striking epithelioid appearance, mimicking a carcinoma or a melanoma. Awareness of BSCs can prevent serious misdiagnoses.

Reticulin Loss in Benign Fatty Liver

Reticulin stains are commonly used in surgical pathology to assess mass lesions for the possibility of hepatocellular carcinoma. The loss of normal reticulin staining can help support a diagnosis of hepatocellular carcinoma, and this stain has proven to be particularly helpful on limited biopsies and fine-needle aspirates. However, an underappreciated diagnostic pitfall is that non-neoplastic liver tissue can also show reticulin loss when there is fatty change. To further characterize this important diagnostic pitfall, reticulin staining was studied in cases of nonalcoholic steatosis, nonalcoholic steatohepatitis, and hepatic adenomas with fatty change. A total of 112 cases with varying degrees of steatosis were collected from 4 academic centers, including 49 cases of steatosis, 49 cases of steatohepatitis, and 14 hepatic adenomas with fatty change. Steatosis was graded as mild (5% to 30% macrovesicular steatosis), moderate (31% to 60%), and marked (>60%). Reticulin stains were scored as the number of foci with diminished reticulin staining in 10 hpf. A focus of diminished reticulin was scored when the extent of reticulin loss was similar to that seen in hepatocellular carcinomas. In the total study set, 28 cases showed mild steatosis, 40 cases showed moderate steatosis, and 44 cases showed marked steatosis. Interestingly, increasing amounts of fat were associated with decreased reticulin staining. For mild steatosis, reticulin loss was rare, with the number of foci of reticulin loss per 10 hpf averaging 0.8 (range, 0 to 3); however, this increased for moderate steatosis, which showed a mean of 3.0 foci per 10 hpf (range, 0 to 5), and was most prominent with marked steatosis, which showed an average of 5.8 foci of reticulin loss per 10 hpf (range, 5 to 8). An almost identical pattern was seen in cases of nonalcoholic steatohepatitis. Overall, reticulin loss was not associated with the degree of inflammation or with the presence or absence of balloon cell change. Reticulin loss also did not correlate with fibrosis stage. In hepatic adenomas, reticulin loss was seen only in areas of fatty change, and decreased reticulin again paralleled the amount of steatosis, with more prominent reticulin loss in those cases with marked steatosis. In conclusion, reticulin loss that reaches levels seen in hepatocellular carcinoma can be seen focally in benign liver tissues with fatty change. Overall, loss of reticulin is more common and more extensive with marked fatty change and does not seem to be linked to inflammation or fibrosis stage. Loss of reticulin can also be seen in hepatic adenomas with fatty change. Increased awareness of this important diagnostic pitfall will help prevent overcalling of reticulin loss when evaluating biopsies and resections of hepatic neoplasms with fatty change.