Diagnostic utility of fine-needle aspiration cytology in syphilitic lymphadenitis: A case report.

Syphilis is a sexually transmitted infection that causes serious health problems without treatment. Detection of syphilis is necessary to stop the spread of the infection. Cytological screeners and pathologists may experience fine-needle aspiration cytology (FNAC) for syphilitic lymphadenitis; however, its characteristic cytological features are rarely reported. We present FNAC cytological features of syphilitic lymphadenitis in a case of a 21-year-old man. He presented with a sore throat and painful neck lymphadenopathy. His swollen and painful neck persisted even with antibiotic treatment. Necrotizing lymphadenitis and lymphoma were clinically suspected. FNAC was taken from the swollen lymph node. Cytologic findings of the specimen showed various inflammatory cells with small-sized vessels arranged in a branching/arborizing fashion. The vessels were surrounded by inflammatory cells, including plasma cells, neutrophils, and macrophages. Perivascular plasma cell cuffing was focally seen along with inconspicuous granulomas. Neutrophils appeared to involve the vascular wall. The cytological findings suggested syphilitic lymphadenitis, and clinical findings and serological tests confirmed primary syphilis with concomitant human immunodeficiency virus infection. Branching/arborizing vessels associated with many plasma cells, vascular involvement of neutrophils, and granulomas may suggest syphilitic infection if the specimen is obtained via FNAC. (189 words).

Cytological findings of ROS1-rearranged lung adenocarcinoma.

ROS1-rearranged lung adenocarcinoma has been recently identified. We report a case of ROS1-rearranged lung adenocarcinoma with special emphasis on cytological findings. Here, we report a case of young woman with ROS1-rearranged lung adenocarcinoma diagnosed by cytology and discuss the clinical, cytological, and molecular findings. Cytologically, the tumor consisted of small tight clusters of cells with high nuclear/cytoplasmic ratio. Nuclei were enlarged and small nucleoli were occasionally observed. Signet-ring cells were focally identified. Neoplastic cells were positive for ROS1 immunocytochemistry. Subsequently, the translocation of ROS1 gene was confirmed in a histological specimen. In conclusion, the specific histology of adenocarcinoma on cytological materials should promote testing for ROS1 immunohistochemistry. Immunocytochemical detection of ROS1 protein helps identify patients suitable for molecular targeted therapy.

Cytological features in eight patients with ALK-rearranged lung cancer.

BACKGROUND: ALK-rearranged lung cancer has been recently identified. Although signet-ring cell morphology and mucinous cribriform pattern are considered to be characteristic of ALK-rearranged lung cancer. Some studies have also suggested cytological features. METHODS: This study investigated cytological features of ALK-rearranged lung cancer in eight patients. RESULTS: Cytologically, the tumor cell group varied from isolated to large clusters. Small nucleoli, fine granular to vesicular chromatin, and nuclear groove were observed in all patients. Furthermore, extracellular and intracellular mucin and signet-ring cells were identified in five patients. CONCLUSION: This study demonstrated that the presence of extracellular and intracellular mucin, signet-ring cells, small nucleoli, fine granular to vesicular chromatin, and nuclear groove in cytological samples may be a diagnostic clue for ALK-rearranged lung cancer.

Imprint cytologic and immunocytochemical findings of sclerosing pneumocytoma.

To the best of our knowledge, there is no description on immunocytochemical study of sclerosing pneumocytoma (SP) using a cell transfer method. In this article, we report imprint cytological and immunocytochemical findings of SP. Three cases of SP possessing both imprint cytological and histological materials were examined. All tumors showed well-defined margin grossly. On microscopic examination, the tumor consisted of surface and stromal round cells. Cytologically, surface and stromal round cells showed fragments or clusters of papillary configuration with low N/C ratio and cell clusters of small to medium-sized cells with high N/C ration. Immunocytochemically, surface cells showed the positive reaction for surfactant apoprotein A (SPA), but stromal round cell exhibited the negative reaction for SPA. Cytologists and pathologists should steadily recognize cytological findings of surface and stromal round cells of SP. Immunocytochemistry of SPA may be useful in the discrimination of both cells. Diagn. Cytopathol. 2017;45:274-278. © 2016 Wiley Periodicals, Inc.

Smear cytology findings of large cell neuroendocrine carcinoma of the uterine cervix.

Large cell neuroendocrine carcinoma (LCNEC) of the uterine cervix is a rare tumor. Moreover, there are only three reports to date that have focused on the cytologic findings of cervical LCNEC. We report the case of a 59-year-old Japanese woman with cervical LCNEC combined with small cell carcinoma (SmCC). Cytologic specimens from the uterine cervix demonstrated large cells with coarse chromatin and prominent nucleoli. Frequent mitotic figures were also observed. Curettage of the uterine endometrium revealed an endometrioid adenocarcinoma with squamous differentiation; i.e., an adenoacanthoma. Histologic examination of surgically resected uterine cervical tissue revealed LCNEC with minor foci of SmCC. Neuroendocrine differentiation in LCNEC was confirmed by immunohistochemistry for synaptophysin and CD56. Cytotechnologists or pathologists need to consider a differential diagnosis of LCNEC while examining cervical cytologic specimens; therefore, it is important to correctly identify the cytologic characteristics of this tumor.

Re-evaluation of histological type by immunohistochemical and genetic study of transcription factors (TFE3 and TFEB) of VHL gene mutation-negative clear cell renal cell carcinoma and other special types of renal tumor.

Translocation-type renal carcinoma has been recently discovered, and it is possible that this tumor may have been previously diagnosed as other types of renal tumor. We have subjected 41 renal tumors, including VHL gene mutation-negative clear cell renal cell carcinoma (RCC), papillary RCC, and chromophobe RCC, to immunohistochemistry of transcription factor E3 (TFE3) and TFEB. All tumors were histologically evaluated by additional immunohistochemical study. As a result, 5 tumors showed a positive reaction for TFE3 with a range from 1+ to 2+ in intensity. No tumors were positive for TFEB. In 5 tumors immunohistochemically positive for TFE3, chimeric transcripts including ASPL-TFE3, PRCC-TFE3, CLTCTFE3, PSF-TFE3, or Nono-TFE3 were not detected. The diagnosis of 6 tumors was changed by reevaluation through retrospective histological and immunohistochemical study. In 4 of 6 tumors, the diagnosis of clear cell RCC was changed to chromophobe RCC. In 1 tumor, oncocytoma was detectable, and RCC with rhabdoid features and sarcomatoid changes was detected in 1 tumor. Finally, the cutoff value of TFE3 immunohistochemistry should be more than 2+ with a wide range. The translocation-type renal carcinoma seems to be quite rare.

Lymphoepithelioma-like carcinoma of the stomach associated with adenosquamous carcinoma.

Lymphoepithelioma-like carcinoma and adenosquamous carcinoma of the stomach are relatively rare tumors. To date, there are no reports on lymphoepithelioma-like carcinoma of the stomach associated with adenosquamous carcinoma. We report herein the first case of such a tumor. A 67-year-old Japanese man presented with dull epigastralgia. The gastric endoscopy revealed an ulcerative cancerous lesion of the upper portion. Histological examination of the gastric tumor showed the coexistence of lymphoepithelioma-like carcinoma and adenosquamous carcinoma. The former showed a positive reaction for Epstein-Barr virus-encoded RNA (EBER). Neoplastic cells of the latter were immunoreactive for p63 and keratin 903, and Alcian blue stain detected acid mucin in glandular lumens. This pattern resembled mucoepidermoid carcinoma in the salivary gland. Finally, this is the first case of gastric lymphoepithelioma-like carcinoma associated with adenosquamous carcinoma, and clinicians and pathologists should recognize the presence of such a tumor.

Immunohistochemical application of D2-40 as basal cell marker in evaluating atypical small acinar proliferation of initial routine prostatic needle biopsy materials.

D2-40 has been recently discovered as a lymphatic endothelial cell marker, and some investigators have found that D2-40 is also expressed in myoepithelial cells of salivary gland or breast. In this study, we evaluated D2-40 expression of basal cells and applied D2-40 immunohistochemistry in the combination of P504S, cytokeratin 5, and p63 for ten lesions with atypical small acinar proliferation (ASAP) in initial prostatic needle biopsy. As a result, D2-40 was expressed in basal cells, lymphatic endothelial cells, and some stromal fibroblasts of normal prostatic tissue. Among ten ASAP lesions, the final diagnosis of seven lesions was resolved by combination immunohistochemistry. D2-40 was comparable to cytokeratin 5 and p63 as a basal cell marker, and there were no lesions that failed to provide an accurate final diagnosis using only D2-40 immunohistochemistry without cytokeratin 5 or p63. However, we found some D2-40-positive stromal fibroblasts or D2-40-positive lumen-collapsed lymphatic vessels neighboring atypical glands. Pathologists should pay attention to avoid recognizing these cells as basal cells. In conclusion, the combination of immunohistochemistry of P504S, cytokeratin 5, p63, and D2-40 may contribute to the accurate diagnosis of ASAP in the initial prostatic needle biopsy.

Diagnostic pitfall on the histological spectrum of adult-onset renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion recently has been found. In this article, we demonstrate an unusual features of such a case. A 73-year-old Japanese woman presented with macroscopic hematuria. The imaging examinations disclosed the renal tumor. Histological examination showed the finding of ASPL-TFE3 RCC, which was characterized by papillary, alveolar, or solid growth of voluminous cell with clear and eosinophilic cells, and stromal psammoma body and hyaline nodules. Additionally, shrunken nuclei, thick cell border, and perinuclear clearing characteristic of chromophobe renal cell carcinoma were observed in the alveolar growth area and the transitional zone between stromal hyalinization, and osseous metaplasia was identified. Immunohistochemically, nuclei of tumorous cell were diffusely positive for TFE3. A RT-PCR study revealed the ASPL-TFE3 chimeric transcript. Finally, pathologists should recognize that the histology of RCC associated with Xp11.2 translocation/TFE3 gene fusion may focally resemble that of chromophobe RCC, but TFE3 immunohistochemistry and molecular genetic study may be helpful in the differential diagnosis. Moreover, osseous metaplasia as well as psammoma bodies should be added to the histological spectrum of the stromal change in RCC associated with Xp11.2 translocations/TFE3 gene fusions.

Solid papillary carcinoma of the breast: imprint cytological and histological findings.

Solid papillary carcinoma is a rare breast lesion, but this entity remains poorly recognized. In this article, we report a case of solid papillary carcinoma of the breast with focus on cytological and histological findings. A 66-year-old Japanese woman presented with nipple discharge. Imprint cytology obtained from the surgically resected breast specimens showed a plasmacytoid appearance and spindle cell morphology with low-grade atypia. Histologically, the tumor revealed findings of solid papillary carcinoma and predominantly showed an intraductal lesion with focal minimal invasion into the breast parenchyma. Fibrovascular cores with hyalinization were seen. Proliferation of short spindle cells was also focally observed. Pseudorosette formation or nuclear palisading at the stromal-glandular interface was seen, and intracellular or extracellular mucin deposition was occasionally identified. Nuclear atypia generally showed low grade. Finally, clinicians, cytotechnologists, and pathologists should recognize this rare tumor entity because this tumor is a malignant neoplasm showing characteristic pathological findings.

Hybrid sclerosing adenosis and basal cell hyperplasia of the prostate.

Hybrid sclerosing adenosis and basal cell hyperplasia of the prostate is a rare lesion. Here we report the seventh case of such lesions. Histological examination of the transurethral resection of the prostate of a 83-year-old Japanese man showed a small lesion consisted of sclerosing adenosis and basal cell hyperplasia, in addition to the diffuse glandular and fibromuscular hyperplasia. Immunohistochemically, many basal cells in sclerosing adenosis and basal cell hyperplasia areas showed a positive reaction for p63, cytokeratin 5, and D2-40. Additionally, many basal cells in the sclerosing adenosis area and some basal cells in the basal cell hyperplasia area were positive for S-100 protein and alpha-smooth muscle actin, which are myoepithelial cell markers. Finally, we suggest that hybrid sclerosing adenosis and basal cell hyperplasia may be actually a special form of hyperplastic lesion of all components of prostatic tissue, reflecting the unbalanced distribution of glandular, stromal (sclerosing adenosis), and basal cell hyperplasia with the differentiation toward myoepithelial cells predominantly occurring in a sclerosing adenosis area. Additionally, this case showed that D2-40 is a useful marker of basal cells.

Chronic sclerosing pyelitis with an increased number of IgG4-positive plasma cells.

IgG4-related disease has been recently described. This disease occurs in various anatomic locations including pancreas, biliary tract, liver, retroperitoneum, kidney, breast, lung, thyroid gland, prostate, salivary gland, lacrimal gland, and lymph node. In this article, we report the first case of IgG4-related disease arising in the renal pelvis. A 49-year-old Japanese woman was found to show left hydronephrosis by a medical checkup. Histological examination of the renal pelvic tumor showed IgG4-related disease. Her postoperative serum IgG4 was elevated, and this was compatible with IgG4-related disease. Systemic examination showed swelling of major and minor salivary glands and the lacrimal glands, and biopsy of the minor salivary gland revealed the finding of IgG4-related disease. Finally, pathologists and clinicians should be aware of the possibility that the renal pelvis may be involved in IgG4-related systemic disease.

Application of immunocytochemistry to the diagnosis of primary epithelioid angiosarcoma of the lung.

Pulmonary epithelioid angiosarcoma is rare, and there are no descriptions of the immunocytochemistry of such a case. We report a case with focus on immunocytochemistry of imprint cytological specimens here. A 43-year-old Japanese man presented with cough. Brushing cytology of the tumor using a bronchoscope showed a malignant neoplasm. Subsequently, left lower lobectomy was undertaken. Imprint cytological material of the neoplastic cells noted some clusters of round, or oval, to polygonal epithelioid cells. Histological examination showed the proliferation of epithelioid neoplastic cells containing erythrocytes in the cytoplasm. The immunocytochemistry in imprint cytological specimens showed a focal positive reaction for von Willebrand factor, and the immunohistochemistry of the surgically resected lung tumor showed a focal positive reaction for Fli-1, von Willebrand factor, CD31, and CD34. Finally, we suggest that the immunocytochemical study of imprint cytological materials may supply available information in diagnosing angiosarcoma with epithelioid features lacking characteristic structures.

Clear cell chondrosarcoma: an ultrastructural study.

Clear cell chondrosarcoma (CCC) is a rare neoplasm. We report here a case of CCC. A 67-year-old Japanese man presented with right arthralgia for 1 year, and histological examination of the subsequent surgical resection of the right femoral bone showed the finding of CCC. Ultrastructurally, most organelles were observed in the perinuclear area. Clear neoplastic cells contained many glycogen particles in the area of the cytoplasm lacking organelles, although glycogen particles overall seemed to be evenly distributed in the cytoplasm. Some mitochondria, Golgi complex, actin-like filaments, and rough endoplasmic reticulum were also demonstrated in the cytoplasm of clear cells. Well-developed microvilli were also seen on the surface of neoplastic cells. These structures in neoplastic cells corresponded notably to structures of normal chondrocytes. Finally, our ultrastructural findings support further evidence that clear cells in CCC may show chondrocyte differentiation and a lack of an organelles area as well as abundant glycogen particles, may contribute to the clear cell morphology in CCC.

Adult-onset renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusion with smooth muscle stroma and abnormal vessels.

Renal cell carcinoma (RCC) associated with Xp11.2 translocation/TFE3 gene fusion has been recently identified. Herein is presented a case of RCC with Xp11.2 translocations/TFE3 gene fusions with unusual histological findings. A 68-year-old Japanese woman was incidentally found to have a renal mass on CT. Histological examination showed clear cell neoplasm with alveolar and papillary growth patterns. The nuclear atypia corresponded to Fuhrman grade 3. Additionally, smooth muscle stroma was observed and abnormal vessels showing a heterogeniety in thickness were also identified. On immunohistochemistry, neoplastic cells were diffusely positive for transcription factor E3 (TFE3) and Melan A, and focally positive for CD10 and RCC marker. The smooth muscle stroma was positive for alpha-smooth muscle actin and h-caldesmon, but reverse transcription-polymerase chain reaction of the tumor using frozen material could not detect any previously reported chimeric transcripts including ASPL-TFE3, PRCC-TFE3, CLTC-TFE3, PSF-TFE3 or NoNo-TFE3. G-band karyotype was unsuccessful. Pathologists should pay attention to the afore-described unusual stromal reaction of adult-onset RCC associated with Xp11.2 translocations/TFE3 gene fusions.

The majority of triple-negative breast cancer may correspond to basal-like carcinoma, but triple-negative breast cancer is not identical to basal-like carcinoma.

Recently, the concept of basal-like carcinoma has been proposed. However, there are only a few reports about the relationship between triple-negative cancer and basal-like carcinoma. In this article, we report the study of the expression of basal cell markers in 11 triple-negative cancers. Eight tumors (4 metaplastic carcinomas, 2 invasive ductal carcinomas, 1 invasive papillary carcinoma, and 1 medullary carcinoma) were positive for more than three markers among cytokeratins 5, 14, and 17, and p63. Three tumors (2 invasive ductal carcinomas and 1 apocrine carcinoma) were completely negative for all markers. Among 8 tumors positive for basal markers, cytokeratins 5 and 17 were expressed in all 8 tumors, cytokeratin 14 in 6 tumors, and p63 in 7 tumors. Finally, we conclude that the majority of triple-negative cancer may correspond to basal-like carcinoma, but the two entities are not identical. The use of combination immunohistochemistry including cytokeratins 5, 14, and 17 and p63 may contribute to the detection of basal-like carcinoma.

Ureteral small cell carcinoma.

Ureteral small cell carcinoma is very rare; only eight cases have been reported in the literature. In this article, we report the ninth case of ureteral small cell carcinoma. A 79-year-old Japanese man presented with asymptomatic macrohematuria, and left nephroureterectomy was performed. The nonpapillary and broad-based tumor, which measured 3.7 x 3.7 x 2.0 cm, was seen in the lower portion of the left ureter just above the ureteral orifice. Microscopically, the tumor was composed of urothelial carcinoma and small cell carcinoma. Immunohistochemically, neoplastic cells of small cell carcinoma were focally positive for chromogranin A. In the normal ureteral mucosa adjacent to the tumor, some endocrine cells positive for chromogranin A and synaptophysin were identified. In conclusion, we suggest that endocrine cells in the ureteral urothelial epithelium may be precursor cells of ureteral small cell carcinoma.

Coexistent adenomyoepithelioma and invasive ductal carcinoma of the breast: presentation as separate tumors.

Adenomyoepitheliomas are rare breast tumors. We report an unusual case of adenomyoepithelioma associated with invasive ductal carcinoma here. Histologically, the lesion consisted of two separate tumors. One nodule corresponded to invasive ductal carcinoma consisting of tubular and trabecular arrangements of columnar or cuboidal neoplastic cells. The other tumor corresponded to adenomyoepithelioma consisting of an inner layer of neoplastic cells with basophilic cytoplasm and the outer layer of neoplastic cells with clear cytoplasm. Immunohistochemically, some myofibroblasts were observed in the stroma of both adenomyoepithelioma and invasive ductal carcinoma, but no CD34-positive stromal cells were seen in the stroma of either lesion. The stromal reaction of adenomyoepithelioma resembles that of intraductal papilloma in the previous study. To the best of our knowledge, this is the first case of coexistent adenomyoepithelioma and invasive ductal carcinoma of the breast that were discovered as separate nodules. Clinicians and pathologists should be aware of such an association because they need to distinguish such a case from malignant neoplasms arising in adenomyoepithelioma. Additionally, our preliminary report suggests that the stromal response of adenomyoepithelioma may resemble that of intraductal papilloma.

Elastofibroma: a histochemical, immunohistochemical, and ultrastructural study of two patients.

Elastofibroma is a rare neoplasm. In this article, we report our study of the pathogenesis of fibrosis in elastofibroma. Three tumors obtained from two patients were selected. One patient was a 57-year-old Japanese woman who had a bilateral tumor, and the other patient was a 83-year-old Japanese man. All tumors occurred in the infrascapular region. Macroscopically, the cut surface of all tumors showed a poorly defined and whitish mass with yellowish foci. Microscopically, the tumor consisted of collagen fiber bundles, abnormal elastic fibers, and spindle cells suggestive of fibroblasts. Elastica-van Gieson and Masson-trichrome stain identified abnormal elastic fibers and abundant collagen fibers, respectively, in elastofibroma. Immunohistochemically, fibroblasts were positive for CD34 but negative for alpha-smooth muscle actin and h-caldesmon. Additionally, the cytoplasm of many fibroblasts was positive for TGF-beta in all tumors. Ultrastructurally, some fibroblasts with abundant organelles in one tumor were observed in the adjacent area to amorphous elastic mass and bundles of collagen fibers. However, no myofibroblasts were ultrastructurally identified in the tumor. Finally, our study supplies further evidence that elastofibroma may show the proliferation of CD34-positive fibroblasts and contain no myofibroblasts, and that fibroblasts may produce both abnormal elastic fibers and collagen fibers through the secretion of TGF-beta.

Sarcomatoid acquired cystic disease-associated renal cell carcinoma.

In this article, we report a rare case of hitherto undescribed acquired cystic disease (ACD)-associated renal cell carcinoma (RCC) with sarcomatoid change. A 78-year-old woman had been receiving hemodialysis for fourteen years at the time when a renal tumor was encountered on the follow-up examination of the kidney. Microscopically, oncocytic cuboidal cells proliferated with tubular, cribriform or papillary growth patterns, and atypical columnar cells with abundant cytoplasm proliferated with papillary configuration. Oxalate crystal deposition was observed in the stroma and the tumor focally resembled translocation type (TFE3) RCC. Sarcomatous neoplastic cells were also seen. The cytoplasm of oncocytic and sarcomatous neoplastic cells was diffusely positive for anti-mitochondrial antibody and the ultrastructural examination detected many mitochondria in the cytoplasm of oncocytic carcinoma cells and sarcomatous neoplastic cells. The loss of chromosomes 1p, 2q11-22, 9 and 14 was observed using comparative genomic hybridization analysis. We thus report here a case of hitherto undescribed ACD-associated RCC intermingled with oncocytic cells, translocation type RCC-like area and sarcomatoid change. This is the sixth case of sarcomatoid RCC arising in end-stage kidney disease.