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Uterine PEComas often present a diagnostic challenge as they share morphological and immunohistochemical features with smooth muscle tumors. Herein we evaluated a series of 19 uterine PEComas to compare the degree of melanocytic marker expression with their molecular profile. Patients ranged from 32–77 (median 48) years, with six tumors classified as malignant based on the modified gynecologic-specific prognostic algorithm. All patients with malignant PEComas were alive with disease or dead of disease at last follow-up, while all those of uncertain malignant potential were alive and well (median follow-up, 47 months). Seventeen of 19 (89%) PEComas harbored either a TSC1 or TSC2 alteration. One of the two remaining tumors showed a TFE3 rearrangement, but the other lacked alterations in all genes evaluated. All showed at least focal (usually strong) positivity for HMB-45, with 15/19 (79%) having >50% expression, while the tumor lacking TSC or TFE3 alterations was strongly positive in 10% of cells. Melan-A and MiTF were each positive in 15/19 (79%) tumors, but staining extent and intensity were much more variable than HMB-45. Five of six (83%) malignant PEComas also harbored alterations in TP53, ATRX, or RB1, findings not identified in any tumors of uncertain malignant potential. One malignant PEComa was microsatellite-unstable/mismatch repair protein-deficient. In summary, TSC alterations/TFE3 fusions and diffuse (>50%) HMB-45 expression are characteristic of uterine PEComas. In morphologically ambiguous mesenchymal neoplasms with myomelanocytic differentiation, especially those with metastatic or recurrent disease, next-generation sequencing is recommended to evaluate for TSC alterations; as such, patients can be eligible for targeted therapy.

Herein we evaluated a series of 21 embryonal rhabdomyosarcomas of the uterine corpus (ucERMS), a rare neoplasm, to characterize their morphology, genomics, and behavior. Patients ranged from 27 to 73 (median 52) years and tumors from 4 to 15 (median 9) cm, with extrauterine disease noted in two. Follow-up (median 16 months) was available for 14/21 patients; nine were alive and well, four died of disease, and one died from other causes. Most tumors (16/21) showed predominantly classic morphology, comprised of alternating hyper- and hypocellular areas of primitive small cells and differentiating rhabdomyoblasts in a loose myxoid/edematous stroma. A cambium layer was noted in all; seven had heterologous elements (six with fetal-type cartilage) and eight displayed focal anaplasia. The remaining five neoplasms showed only a minor component (

Teratomas are tumors of germ cell origin, and in the female genital tract are subclassified as immature or mature based on the presence or absence, respectively, of immature elements. Somatic tumors may also develop in association with teratomas, and most commonly include thyroid tumors, carcinoids and carcinomas. We report herein 2 rare forms of gynecologic teratomas: 1 case of immature teratoma of the uterus and 1 case of a benign follicular hamartoma arising in association with mature cystic teratoma of the ovary.

Verruciform proliferations of the vulva unrelated to HPV infection are rare. The term differentiated exophytic vulvar intraepithelial lesion (DEVIL) was recently proposed for these lesions, which harbor recurrent PIK3CA mutations. It is still unclear whether DEVIL is related to verrucous carcinoma, a neoplasm characterized by persistence and local recurrence but nil risk of distant spread. Specimens identified using the words “verruciform” and “verrucous” were reviewed. Diagnosis of DEVIL required verruciform acanthosis, hyper and/or parakeratosis, hypogranulosis, cytoplasmic pallor, and bland nuclei. Verrucous carcinoma required, in addition, discontinuous, bulbous, puzzle-like nests in the stroma. A targeted next-generation sequencing using a custom 11-gene panel was performed. Eighteen specimens corresponding to ten patients with DEVIL and/or verrucous carcinoma were included. Median age at presentation was 66 years for DEVIL and 70 years for verrucous carcinoma. A similar spectrum of prevalent mutations was found in both lesions involving HRAS, PIK3CA, and BRAF. DEVIL preceded verrucous carcinoma and/or was diagnosed concurrently or in subsequent follow-up in five patients. In four of these, the same mutation was identified in DEVIL and synchronous or metachronous carcinoma. All cases showed wild-type 53 staining and lacked pathogenic TP53 mutations. DEVIL is a rare form of squamous proliferation characterized by prevalent PIK3CA and HRAS mutations. Its temporal relationship with verrucous carcinoma and their shared mutational profile in some patients suggest that DEVIL is a precursor of verrucous carcinoma. Moreover, given their morphologic and molecular overlap and the nil risk of verrucous carcinoma for distant spread, it is conceivable that DEVIL and verrucous carcinoma represent a spectrum of the same entity.

SMAD4 is a tumor suppressor gene that plays a role in cancer initiation and progression. A few studies have explored the value of immunohistochemistry for SMAD4 in gynecologic neoplasms, mainly in the ovary. However, literature is sparse when it comes to other sites such as endometrium and cervix, as well as in benign and borderline ovarian mucinous neoplasms. The aim of this study was to assess the expression of SMAD4 in various gynecologic tumors. We selected primary gynecologic tumors comprising a spectrum of neoplasms showing mucinous differentiation. Few cases of metastatic tumors were also included. A total of 103 cases were retrieved, including tumors of ovarian origin (13 mucinous adenocarcinomas, 9 mucinous borderline tumors, 19 mucinous cystadenomas, and 3 mucinous tumors arising from teratomas), 36 of endometrial origin (23 endometrioid adenocarcinomas with mucinous differentiation and 13 mucinous adenocarcinomas), 17 cases of cervical carcinoma (16 of usual type and 1 of gastric type), and 6 metastatic adenocarcinomas to ovary. SMAD4 immunohistochemistry was retained in most primary tumors, except in 3 endocervical adenocarcinomas (2 usual-type, 1 gastric-type) and in one mucinous carcinoma arising from an ovarian teratoma. Of the 6 metastatic cases, 4 showed SMAD4 loss. In summary, retained expression of SMAD4 was seen in 95.8% of primary gynecologic neoplasms. These results can be of utility when dealing with mucinous lesions for which metastatic origin is suspected. Loss of SMAD4 expression virtually excludes primary tumors of endometrial or ovarian origin, but is of less utility when evaluating carcinomas involving the cervix.

The entity "pericytoma with t(7;12)" was described as a rare, distinct perivascular myoid neoplasm provisionally classified within the family of myopericytic tumors that demonstrates t(7;12)(p22;q13) translocation with resultant ACTB-GLI1 fusion and biologically was felt to behave in an indolent fashion. However, a recent study showed that tumors with this and similar translocations may have variable morphology and immunohistochemical phenotype with inconsistent myopericytic characteristics and a propensity for metastasis, raising questions regarding the most appropriate classification of these neoplasms. Herein, we report 3 additional patients with tumors harboring t(7;12) and ACTB-GLI1 fusion. The tumors arose in adults and involved the proximal tibia and adjacent soft tissues, scapula and adjacent soft tissues, and ovary. All tumors were composed of round-to-ovoid cells with a richly vascularized stroma with many small, delicate, branching blood vessels, where the neoplastic cells were frequently arranged in a perivascular distribution. Both tumors involving bone showed histologic features of malignancy. By immunohistochemistry, all tested tumors were at least focally positive for smooth muscle actin (3/3) and CD99 (patchy) (2/2), with variable staining for muscle-specific actin (2/3), S100 protein (1/3), epithelial membrane antigen (2/3), and pan-keratin (1/3); all were negative for desmin and WT1 (0/3). The 2 patients with bone tumors developed metastases (27 and 84 mo after diagnosis). Whether these tumors are best classified as malignant myopericytoma variants or an emerging translocation-associated sarcoma of uncertain differentiation remains to be fully clarified; however, our study further documents the potential for these tumors to behave in an aggressive fashion, sometimes over a prolonged clinical course.

Wilms tumor (WT) is an uncommon malignant neoplasm that occurs predominantly in the kidney of pediatric patients; its extrarenal counterpart is exceedingly rare. We present the case of an adult female diagnosed with uterine WT. Following hysterectomy due to a uterine mass, histopathologic examination demonstrated a triphasic malignancy composed of epithelial, stromal, and blastemal elements. The characteristic morphologic features, which were supported by immunohistochemical analysis, were diagnostic of WT of the uterus. A summary of the main clinicopathologic parameters, along with a review of all previously reported cases, are described.

Recognising metastatic gastrointestinal and pancreatobiliary tumours to gynaecological sites may be challenging, as primary Mullerian tumours can demonstrate similar histological features. Endocervical adenocarcinomas can be of gastric and intestinal types, endometrial lesions may show gastrointestinal phenotype, and finally, mucinous tumours with secondary involvement of the ovaries may mimic primary neoplasms. The aim of this review is to address selected neoplastic entities of the gynaecological tract with gastric and intestinal differentiation and provide helpful clinical and pathological parameters for the diagnosis. A brief overview of metastatic tumours originating from the gastrointestinal and pancreaticobiliary tracts is also provided, including the most common pathological features.

Papillary squamous cell carcinoma is a rare variant of squamous cell carcinoma, histologically characterized by thin or broad papillae lined by epithelium showing the features of high-grade squamous intraepithelial lesion. Given the exophytic nature of these neoplasms, the diagnosis, assessment and quantification of invasion may be difficult in small biopsies. The goal of this study was to determine the presence and extent of cervical stromal invasion by comparing biopsy samples with excisional specimens in a cohort of patients diagnosed with papillary squamous cell carcinoma. Cases were identified from the surgical pathology files between the years 2003 and 2018 and only cases in which the patients underwent an excisional procedure following the diagnostic biopsy were included. Eighteen cases were identified. Patients age ranged 21 to 72 yr (mean: 46.2 yr). Review of the initial, presurgical biopsies showed that 17/18 (94%) patients had no evidence of stromal invasion. In the surgical excision specimens (2 cone biopsies, 1 loop electrosurgical excision procedure, and 15 hysterectomies), 13 cases (76.5%) showed invasive squamous cell carcinoma. Tumor sizes ranged 1.0 to 6.1 cm; stromal invasion ranged in depth 0.2 to 2.2 cm (median: 1.2), and in horizontal length 0.3 to 4.0 cm (median: 2.01). Papillary squamous cell carcinoma is a rare variant of squamous cell carcinoma of the cervix that may impose some diagnostic difficulties in small biopsies. Our findings demonstrated that the significant majority of cases might only show the presence of invasive cancer in excisional samples. Awareness of this data is important to guide proper management and avoid under-treatment.

Background Heart transplant is the gold standard therapy for patients with advanced heart failure. Over 5,500 heart transplants are performed every year worldwide. Cardiac allograft vasculopathy (CAV) is a common complication post-heart transplant which reduces survival and often necessitates heart retransplantation. Post-transplant follow-up requires serial coronary angiography and endomyocardial biopsy (EMB) for CAV and allograft rejection screening, respectively; both of which are invasive procedures. This study aims to determine whether osteopontin (OPN) protein, a fibrosis marker often present in chronic heart disease, represents a novel biomarker for CAV. Methods Expression of OPN was analyzed in cardiac tissue obtained from patients undergoing heart retransplantation using immunofluorescence imaging (n = 20). Tissues from native explanted hearts and three serial follow-up EMB samples of transplanted hearts were also analyzed in five of these patients. Results Fifteen out of 20 patients undergoing retransplantation had CAV. 13/15 patients with CAV expressed nuclear OPN. 5/5 patients with multiple tissue samples expressed nuclear OPN in both 1 st and 2 nd explanted hearts, while 0/5 expressed nuclear OPN in any of the follow-up EMBs. 4/5 of these patients had an initial diagnosis of dilated cardiomyopathy (DCM). Conclusion Nuclear localization of OPN in cardiomyocytes of patients with CAV was evident at the time of cardiac retransplant as well as in patients with DCM at the time of the 1 st transplant. The results implicate nuclear OPN as a novel biomarker for severe CAV and DCM.

Epithelial ovarian cancer represents a group of heterogeneous diseases with high grade serous cancer (HGSC) representing the most common histotype. Molecular profiles of precancerous lesions found in the fallopian tube have implicated this tissue as the presumptive site of origin of HGSC. Precancerous lesions are primarily found in the distal fallopian tube (fimbria), near the ovary relative to the proximal tissue (ampulla), nearer to the uterus. The proximity of the fimbria to the ovary and the link between ovulation, through follicular fluid release, and ovarian cancer risk led us to examine transcriptional responses of fallopian tube epithelia (FTE) at the different anatomical sites of the human fallopian tube. Gene expression profiles of matched FTE from the fimbria and from premenopausal women resulted in differentially expressed genes (DEGs): CYYR1, SALL1, FOXP2, TAAR1, AKR1C2/C3/C4, NMBR, ME1 and GSTA2. These genes are part of the antioxidant, stem and inflammation pathways. Comparisons between the luteal phase (post-ovulation) to the follicular phase (pre-ovulation) demonstrated greater differences in DEGs than a comparison between fimbria and fallopian tube anatomical differences alone. This data suggests that cyclical transcriptional changes experienced in pre-menopause are inherent physiological triggers that expose the FTE in the fimbria to cytotoxic stressors. These cyclical exposures induce transcriptional changes reflective of genotoxic and cytotoxic damage to the FTE in the fimbria which are closely related to transcriptional and genomic alterations observed in ovarian cancer.

Objectives Lymphoepithelioma-like carcinoma (LELC) of the uterine cervix is a rare tumor. The goal of this study was to evaluate a series of cases of cervical LELC and to investigate possible association with human papillomavirus (HPV) and/or Epstein-Barr virus (EBV). Methods Immunohistochemistry for p63, p16, human leukocyte antigen-D related (HLA-DR), and B-cell lymphoma 2 (BCL-2); in situ hybridization (ISH) for EBV and HPV; and polymerase chain reaction (PCR) genotyping were performed. Mismatch repair (MMR) studies and PD-L1 status were obtained. Results We found eight cases of LELC. Tumors demonstrated sheets of cells containing vesicular nuclei, amphiphilic cytoplasm, and dense peri- and intratumoral lymphocytic infiltrates. All tumors stained for p63, p16, and HLA-DR; two also stained for BCL-2. When combining ISH and PCR results, seven tumors were HPV positive; they were all Epstein-Barr encoding region negative. All cases were MMR intact, and most overexpressed PD-L1. Conclusions This study shows that cervical LELCs are associated with HPV and not EBV.

Serous borderline tumors are rare, benign ovarian neoplasms that may recur and undergo malignant transformation to low-grade serous carcinomas (LGSCs). In this report, a 50-year-old female with a remote history of a serous borderline ovarian tumor experienced a recurrence of LGSC, presenting as a large solitary subcutaneous mass anterior to the sternum after a 33-year disease-free interval. The described case highlights the unpredictable nature of this disease and the importance of implementing lifelong surveillance strategies.

Renal tumors are predominantly of epithelial, mesenchymal, or mixed-cell origin. Each category can be subclassified as benign or malignant. Renal cell carcinomas (RCCs; malignant epithelial tumors) encompass a large heterogeneous group of cancers derived mostly from renal cortical cells, accounting for more than 90% of malignancies detected in the kidney. Thus far, more than ten molecular and histopathological distinct subtypes have been described in the literature, and the classification system periodically undergoes revision. The most common RCCs are clear cell renal cell carcinoma and papillary renal cell carcinoma. Non-epithelial tumors include angiomyolipoma and neoplasms of smooth muscle origin (i.e., leiomyoma and leiomyosarcoma). Lastly, mixed epithelial and stromal tumor (MEST) is the hallmark of a biphasic tumor originating in the kidney. Percutaneous renal core biopsies and fine needle aspiration have evolved in regard to technical procedures and diagnostic accuracy, demonstrating excellent rates of sensitivity and specificity. This chapter will describe the most common renal neoplasms, highlighting their main morphologic features and diagnostic immunohistochemical properties.

Perivascular epithelioid cell tumors (PEComa) are rare neoplasms characterized by co-expression of melanocytic and muscle markers. HMB45 and Melan-A are used to confirm a PEComa diagnosis; however, both are often focally expressed and sensitivity for Melan-A is low. PNL2 is a reliable biomarker for epithelioid melanoma and renal angiomyolipoma/PEComa. The objective of this study was to determine PNL2 utility in diagnosing uterine PEComas as well as distinguishing PEComas from uterine smooth muscle tumors (SMTs). Twenty-one uterine PEComas and 45 SMTs were analyzed for PNL2; a subset was also stained for HMB45, Melan-A, Cathepsin-K, Desmin, and h-Caldesmon. Cases were scored as negative (0), focal (10% of tumor cells), or patchy to diffusely positive (10% of tumor cells). PEComas were positive for PNL2, HMB45, and Melan-A in 86%, 100%, and 57% of cases, respectively. In PEComas, PNL2 was patchy to diffusely positive more frequently (10/18, 56%) than Melan-A (4/12, 33%). In contrast, 2 of 45 (4%) SMTs were focally PNL2 positive; HMB45 was focally positive in 4 SMTs (11%) and all were negative for Melan-A. Desmin and h-Caldesmon were positive in 90% and 57% of PEComas, and 91% and 82% of SMTs. Cathepsin-K was positive in 100% of PEComas and 93% of SMTs. PNL2 is a useful biomarker for the diagnosis of uterine PEComa, with comparable sensitivity and specificity to HMB45. In contrast, PNL2 stains more PEComas when compared with Melan-A. Cathepsin-K, Desmin, and h-Caldesmon are of little utility for distinguishing PEComas and SMTs; however, lack of Cathepsin-K argues against PEComa. These results suggest that PNL2 should be used in conjunction with HMB45 in the diagnosis of PEComa of the uterine corpus.

Objectives Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are rare mesenchymal neoplasms of uncertain histogenesis that are challenging to diagnose due to their morphological and immunohistochemical overlap with more conventional entities. While DNA sequencing has failed to identify recurring mutations in these tumors, RNA sequencing recently detected NCOA2/3 fusions in two small series. The objective of this study was to further describe the characteristics of two UTROSCTs. Methods We retrospectively evaluated the clinicopathological and immunohistochemical features of two UTROSCTs, and performed RNA sequencing to detect gene fusions. Results The patients were 52 and 57 years old, tumors measured 5 and 12 cm, and were confined to the myometrium. Both showed multiple histologic patterns including diffuse, cord-like, and trabecular, with rhabdoid cells focally present. One UTROSCT had significant cytologic atypia and brisk mitotic activity, but both lacked necrosis and lymphovascular invasion. Variable immunohistochemical expression for calretinin, inhibin, WT-1, ER, CD10, and pankeratin was noted. RNA sequencing detected an ESR1-NCOA3 fusion in one tumor, whereas the other had a GREB1-NCOA2 rearrangement. The former patient is alive and well five months after diagnosis, while the latter recurred two years later, and is currently alive with disease (six years after original diagnosis). Conclusions The detection of NCOA2/3 fusions in two additional UTROSCTs further supports this rearrangement as a characteristic finding in these rare tumors. Additional studies are warranted to determine its sensitivity and specificity in UTROSCTs compared to other gynecologic neoplasms.

Neuroendocrine (NE) tumours are uncommon in the gynecological tract. In addition to their histological features, what defines NE carcinoma is the expression of markers such as chromogranin, synaptophysin and neural cell adhesion molecule (CD56) by immunohistochemistry (IHC). Although limited data have demonstrated that some high-grade uterine tumours may focally express these markers, the incidence of such labelling in endometrial carcinomas in general is not well known. The goal of this study was to characterise the expression of NE markers in a cohort of endometrial carcinomas. We searched our institutional surgical pathology database for hysterectomy specimens containing endometrial carcinomas. Cases demonstrating classic morphological features of NE carcinomas were excluded. IHC for synaptophysin, chromogranin and CD56 was performed in whole-tissue sections of formalin-fixed, paraffin-embedded (FFPE) tumours. Thyroid transcription factor 1 (TTF-1) was also included, given its positivity in a subset of small cell carcinomas. Marker expression was graded based on percentage of positive tumour cells (0, not detected; 1, 1-25%; 2, 25-50%; 3, >50%). Chi-square was used for statistical analysis and significance was set at p

Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms that may show overlapping morphology and immunohistochemistry with uterine smooth muscle tumors. In this study, we evaluated the morphologic, immunohistochemical, and molecular features of 32 PEComas, including 11 with aggressive behavior. Two distinct morphologies were observed: classic (n=30) and those with a lymphangioleiomyomatosis appearance (n=2). In the former, patients ranged from 32 to 77 (mean: 51) years and 13% had tuberous sclerosis. Tumors ranged from 0.2 to 17 (mean: 5.5) cm with 77% arising in the corpus. Epithelioid cells were present in 100% and a spindled component was seen in 37%. Nuclear atypia was low (53%), intermediate (17%), or high (30%). Mitoses ranged from 0 to 36 (mean: 6) and 0 to 133 (mean: 19) per 10 and 50 high-power fields, with atypical mitoses present in 30%. Thin and delicate vessels were noted in 100%, clear/eosinophilic and granular cytoplasm in 93%, stromal hyalinization in 73%, necrosis in 30%, and lymphovascular invasion in 10%. All tumors were positive for HMB-45, cathepsin K, and at least one muscle marker, with most expressing melan-A (77%) and/or MiTF (79%). A PSF-TFE3 fusion was identified in one while another showed a RAD51B-OPHN1 fusion. Follow-up ranged from 2 to 175 (mean: 41) months, with 63% of patients alive and well, 20% dead of disease, 13% alive with disease, and 3% dead from other causes. In the latter group (n=2), patients were 39 and 49 years old, one had tuberous sclerosis, while the other had pulmonary lymphangioleiomyomatosis. Both tumors expressed HMB-45, cathepsin K, and muscle markers, but lacked TFE3 and RAD51B rearrangements. The 2 patients are currently alive and well. Application of gynecologic-specific criteria (≥4 features required for malignancy: size ≥5 cm, high-grade atypia, mitoses1/50 high-power fields, necrosis, and lymphovascular invasion) for predicting outcome misclassified 36% (4/11) of aggressive tumors; thus, a modified algorithm with a threshold of 3 of these features is recommended to classify a PEComa as malignant.

Although most adrenal tumors are not diagnostic dilemmas, there are cases that are challenging. This may be due to the tissue provided, for example fragmented tissue received in the setting of morcellation, or it may be due to inherently challenging histology, such as in cases with equivocal features of malignancy. Additionally, much has been learned about the molecular alterations of adrenal tumors, especially pheochromocytomas. Many of these alterations represent germline mutations with significant clinical implications for patients and their families. The aim of this review is to provide an overview of the most common adrenal tumors in adults so that pathologists can tackle these interesting tumors.

Infantile fibrosarcoma and congenital mesoblastic nephroma are tumors of infancy traditionally associated with the ETV6-NTRK3 gene fusion. However, a number of case reports have identified variant fusions in these tumors. In order to assess the frequency of variant NTRK3 fusions, and in particular whether the recently identified EML4-NTRK3 fusion is recurrent, 63 archival cases of infantile fibrosarcoma, congenital mesoblastic nephroma, mammary analog secretory carcinoma and secretory breast carcinoma (tumor types that are known to carry recurrent ETV6-NTRK3 fusions) were tested with NTRK3 break-apart FISH, EML4-NTRK3 dual fusion FISH, and targeted RNA sequencing. The EML4-NTRK3 fusion was identified in two cases of infantile fibrosarcoma (one of which was previously described), and in one case of congenital mesoblastic nephroma, demonstrating that the EML4-NTRK3 fusion is a recurrent genetic event in these related tumors. The growing spectrum of gene fusions associated with infantile fibrosarcoma and congenital mesoblastic nephroma along with the recent availability of targeted therapies directed toward inhibition of NTRK signaling argue for alternate testing strategies beyond ETV6 break-apart FISH. The use of either NTRK3 FISH or next-generation sequencing will expand the number of cases in which an oncogenic fusion is identified and facilitate optimal diagnosis and treatment for patients.

Mammary analog secretory carcinoma of salivary gland is a recently described entity with unique morphologic, clinical, and genetic characteristics, including the characteristic t(12;15)(p13;q25) with ETV6-NTRK3 translocation found in secretory carcinomas of the breast. Before their initial description, these salivary gland tumors were generally diagnosed as acinic cell carcinoma or adenocarcinoma. For the purpose of this study, all cases of salivary gland acinic cell carcinoma, cribriform cystadenocarcinoma, and adenocarcinoma, not otherwise specified (NOS), diagnosed over a 10-year period were retrieved from our surgical pathology files. There were a total of 11 cases diagnosed as acinic cell carcinoma, 10 cases of adenocarcinoma, NOS, and 6 cases of cribriform cystadenocarcinoma. All slides were reviewed by two pathologists (AP, CGF) and tumors that show morphologic features of mammary analog secretory carcinoma according to the recent literature were selected. This process narrowed down the initial number to six cases originally diagnosed as acinic cell carcinoma, three cases originally diagnosed as adenocarcinoma, NOS, and one case originally diagnosed as cribriform cystadenocarcinoma. The 10 cases were subjected to immunohistochemistry for S-100, mammaglobin, and ANO1, as well as fluorescence in situ hybridization analysis for t(12;15)(p13;q25) with ETV6-NTRK3 fusion rearrangement. The ETV6-NTRK3 gene rearrangement was detected in three tumors. These three tumors, initially diagnosed as acinic cell carcinomas, stained positive for S-100 and mammaglobin, and negative for ANO1 by immunohistochemistry. Two of the three patients were male (2/3). In summary, mammary analog secretory carcinoma is a newly described diagnostic entity that should be in the differential diagnosis of salivary gland tumors that morphologically mimic other neoplasms, mainly acinic cell carcinomas. They differ from conventional acinic cell tumors immunohistochemically and molecularly. Positivity for mammaglobin and S-100, and negativity for ANO1 are useful screening tools before confirmatory molecular studies.

Genital melanocytic nevus represents a distinct form of melanocytic proliferation, which can exhibit significant atypia, both clinically and histologically. In a background of lichen sclerosus (LS), the histologic changes could be misconstrued as indicative of malignant melanoma. We present herein a case of the atypical genital nevus of childhood complicated by LS, and a review of the literature is performed. Tissue was available for routine light microscopy and immunohistochemical evaluation to assess the expression of soluble adenylyl cyclase. Fluorescent in situ hybridization studies were conducted to assess for abnormalities in Myb1, CCND1, RREB1 and CEP6. The specimen showed an atypical compound melanocytic proliferation arising in a background of LS. The lesion exhibited significant architectural atypia based on the high-density confluent nature of the junctional melanocytic proliferation with epidermal effacement, rare areas of pagetoid ascent, and the heavily pigmented epithelioid quality of the melanocytes. Fluorescent in situ hybridization studies were normal. The soluble adenylyl cyclase antibody preparation demonstrated a benign nevus-like pattern. The lesion was felt to represent an atypical genital melanocytic nevus, which can resemble a partially regressed melanoma in a background of LS. It is very important for the pathologist to be aware of this entity to avoid misdiagnosis.

A 55-year-old HIV-negative white male presented with right ear deafness, right axillary lymphadenopathy, and weight loss. Laboratory findings included anemia, marked leukocytosis, and thrombocytopenia. Examination of the peripheral smear demonstrated the presence of increased circulating blast-like cells of intermediate size, with basophilic cytoplasm and nuclei with open chromatin. MRI of the brain was compatible with hemorrhagic labyrinthitis. Excisional biopsy of the axillary mass revealed an enlarged lymph node with effaced architecture and “starry sky” appearance. The cells expressed CD20, CD10, BCL6, and surface kappa immunoglobulin light chain, with a high proliferative index by immunohistochemistry and flow cytometry. Subsequent bone marrow biopsy was hypercellular (approximately 95%), with blast-like cells virtually replacing all hematopoietic elements. Routine karyotype as well as FISH analysis of bone marrow cells demonstrated rearrangement of the MYC gene at chromosome 8q24 region, IGH/MYC fusion, and additional signal for IGH gene. We present herein a case of sporadic Burkitt lymphoma occurring in a previously healthy HIV-negative male. The unusual clinical findings in this case include the relatively older age at presentation (55 years), an immunocompetent patient who had nodal involvement and leukemic phase of Burkitt, coupled with partial deafness. A brief educational review of this neoplasm is made.

A 59-year-old man with non-ischemic cardiomyopathy underwent orthotopic heart transplantation. The donor, a 31-year-old male declared brain dead after a gunshot wound to the head, was considered high risk due to history of incarceration, illicit drug use, and sex with a HIV-positive partner. At organ procurement, the heart, kidneys, pancreas, and liver looked grossly normal. A small right lower lobe nodule was noticed, and lung biopsy was performed. Bronchoscopy showed purulent secretions in the right lower lobe. Images from pathology are presented. Lung biopsy confirmed the presence of hyalinized cyst wall containing organism-like structures. A combination of culture, microscopic morphology, and gene sequencing was used to identify the causative organism. The patient and all other organ recipients received appropriate antifungal prophylaxis and remain asymptomatic 6 months post-transplant.

Columnar cell variant is a recognized rare variant of papillary thyroid carcinoma (PTC) that has an uncertain clinical course. This variant has two subvariants, and one is regarded as a more aggressive form in comparison to the more common classical and follicular variants. These tumors have morphological resemblance with endometrial or colonic adenocarcinoma. CDX2, a transcription factor of the caudal homeobox family, plays a key role in intestinal development and differentiation, and it is widely used as a marker to detect adenocarcinomas of intestinal and colonic origin. CDX2 has been rarely reported in PTC.We studied 10 cases of columnar cell variant of PTC (CCV-PTC). The histological, architectural, and cytological features fulfilled the diagnostic criteria of the CCV-PTC, as defined by the current World Health Organization classification. Ten patients (six men and four women) ranging in age from 32 to 90 years (mean, 58.3 years) presented with tumors classified as indolent (four cases) or aggressive (six cases); three harbored a BRAF(V600E) mutation. All cases were β-catenin negative. The Ki-67 proliferative index was up to 50%. All cases were thyroid transcription factor-1-positive. Using paraffin-embedded blocks, immunohistochemistry for CDX2 was performed to evaluate the reactivity of this antibody to this variant of PTC.Nuclear positivity for CDX2 was detected in one out of the 10 cases studied (10%); the other nine cases did not express CDX2.Only one of our cases showed nuclear positivity for CDX2. Therefore, our study failed to confirm it as a marker for CCV-PTC. The absence of CDX2 in the majority of the cases does not support the theory of CDX2 playing a role in the intestinal phenotype of these tumors.

When present in thyroid, amyloid is an attribute almost always restricted to medullary thyroid carcinoma. Scant studies in the literature have demonstrated this finding in other thyroid pathologies as papillary thyroid carcinoma, amyloid goiter, and other benign entities. From our experience in thyroid pathology, we analyzed cases on which the stroma contained deposits of amorphous, acellular, and eosinophilic material characteristic of amyloid. Congo red stain on suspicious cases was performed; clinicopathologic investigation was done when results were positive. Seven patients with amyloid infiltration in the thyroid, in association with papillary thyroid carcinoma, and in 4 cases of benign pathologies were found in our own review. The association of amyloid and thyroid is discussed herein, including cases of systemic amyloidosis, malignancies, benign diseases, and thyroid goiter, from our practice and from the available literature.

Correction to: Modern Pathology (2014) 27, 30–37; doi:10.1038/modpathol.2013.84; published online 28 June 2013 In the title of this article, the word ‘analog’ should be ‘analogue.’