Composite FOXL2 Mutation-positive Adult Granulosa Cell Tumor and Serous Borderline Tumor of the Ovary.

We report a case of a cystic ovarian neoplasm in a 76-yr-old female composed of 2 distinct and intimately associated components: a macrocystic adult granulosa cell tumor (AGCT) and a serous borderline tumor. The granulosa cell nature of the tumor was confirmed with positive immunohistochemical staining for inhibin, calretinin, and WT1, while the neoplastic nature of the granulosa cell proliferation was supported by the presence of a point mutation of the FOXL2 gene. A review of 19 previously reported mixed AGCT and epithelial neoplasms of the ovary is included. Of the eight mixed AGCT and epithelial tumors, including our case, that were tested for FOXL2 mutation, 4 of the 5 mutation-positive cases were notable for demonstrating a macroscopically visible nodule or mass of AGCT at the time of gross examination, while 2 of the 3 mutation-negative cases lacked a mass-producing granulosa cell component. This feature by itself may be sufficient to predict the true neoplastic nature of the granulosa cell proliferation. This is the first reported case of a composite neoplastic AGCT and serous borderline tumor. We also discuss the current histogenetic models for these rare mixed AGCT and epithelial tumors.

Hepatic pseudotumor associated with Strongyloides infection: A case report.

BACKGROUND: Strongyloides sterocoralis is a parasitic infection caused by a roundworm that is transmitted through soil contaminated with larvae. It can infrequently cause hepatic abscesses in immunocompromised patients and is rarely reported to form hepatic lesions in immunocompetent hosts. CASE SUMMARY: We present a case study of a 45-year-old female who presented with right upper quadrant abdominal pain and constitutional symptoms for several weeks. Cross-sectional imaging identified several malignant-appearing liver masses. Further investigation, including serological testing and histopathologic examination, revealed the presence of serum Strongyloides antibodies and hepatic granulomas with extensive necrosis. Following treatment with ivermectin for 2 wk, there was complete resolution of the liver lesions and associated symptoms. CONCLUSION: This case highlights the importance of considering parasitic infections, such as Strongyloides, in the differential diagnosis of hepatic masses. Early recognition and appropriate treatment can lead to a favorable outcome and prevent unnecessary invasive procedures. Increased awareness among clinicians is crucial to ensure the timely diagnosis and management of such cases.

Pulmonary squamous cell carcinoma with a lepidic-pagetoid growth pattern.

We report a rare case of a peripheral squamous cell carcinoma (SCC) of the lung in which most of the tumor displayed a "lepidic" growth pattern. The tumor cells also appeared to grow along the alveolar walls between the overlying pneumocytes and underlying basement membrane, a form reminiscent of the "pagetoid" mode of spread. The neoplastic cells were positive for the squamous markers p63 and p40. TTF-1 and CK7 highlighted residual non-neoplastic pneumocytes, which either covered the lepidic tumor cells or lined pseudoglandular formations created by the filling of alveolar spaces by the tumor. CK7 also stained the tumor cells, albeit focally and weakly, a not uncommon finding in peripheral lung SCC. The tumor cells were negative for TTF-1 (clone 8G7G3/1), but did show focal weak reactivity with the less specific clone SPT24. The invasive area measured 2.5 mm while the overall size of the tumor including the lepidic-pagetoid component was 9.0 mm. Even though the invasive component was < 0.5 cm, the only option according to existing staging criteria was to stage it as pT1a. Since the current staging system does not account for the non-invasive lepidic component of pulmonary SCC, the increasing awareness of this variant may require its inclusion within the classification and pathological staging of lung carcinoma.

Pagetoid involvement of bronchioles by metastatic breast carcinoma.

We report a case of a 36-year-old female with endobronchiolar spread of breast carcinoma in the lung. The patient had recently been diagnosed with invasive ductal breast carcinoma and imaging of the lungs revealed bilateral lung nodules. She then underwent a wedge resection of a lung nodule. The biopsy revealed a subpleural metastatic nodule of invasive ductal carcinoma with an intra-alveolar pattern of spread at its advancing edge. Several smaller foci of intra-alveolar tumor were noted as well as pagetoid spread of tumor cells along a 0.9 mm wide bronchiole. The neoplastic cells were TTF-1 negative, GATA3 positive and ER positive. This is the third reported case of pagetoid spread of metastatic breast carcinoma along the bronchial tree. This case emphasizes the importance of examining not only bronchi but also bronchioles to detect this unusual pattern of spread of metastatic breast carcinoma in lung resection specimens.

Perineal Clear Cell Hidradenoma: A GATA3-positive Neoplasm With Potential for Misdiagnosis.

We report a case of clear cell hidradenoma of the perineum that was initially misinterpreted as a papillary urothelial carcinoma, either metastatic or of Bartholin gland origin, on initial excisional biopsy. The misinterpretation may have been due to the pseudopapillary architecture and GATA3-positivity of the biopsy tissue. Clear cell hidradenomas often show a range of histologic growth patterns and cellular differentiation and are one of many tumors that react immunohistochemically with GATA3. Although rare, these tumors can occur in the genital region and can mimic malignant tumors such as metastatic renal cell carcinoma and carcinomas of the genitourinary tract. This report details the morphologic and immunohistochemical pitfalls that make accurate diagnosis of clear cell hidradenoma in this unusual location challenging.

Ciliated Carcinoma of the Endometrium.

We report a case of ciliated carcinoma of the endometrium in a 55-yr-old woman with stromal hyperthecosis of the ovaries. The patient presented with postmenopausal uterine bleeding and an endometrial curetting revealed an atypical epithelial proliferation that met the criteria for endometrioid adenocarcinoma notwithstanding an abundance of ciliated cells. Cilia were present not only within typical endometrioid glands but also within microacini of quasi-solid areas as well as inside intracytoplasmic vacuoles. The subsequent hysterectomy specimen demonstrated a well-differentiated adenocarcinoma of the endometrium with a predominance of neoplastic glands lined by ciliated epithelial cells, thus confirming the initial suspicion for ciliated carcinoma. Since the first description of ciliated adenocarcinoma of the endometrium in 1983, only a handful of additional cases have been reported in the literature. We review the spectrum of histologic presentations of this endometrial neoplasm and elaborate on its distinction from cilia-bearing mimickers and its histogenesis.

Metachronous Mesorectal Recurrence after Colectomy for Ascending Colon Cancer.

BACKGROUND: An isolated metachronous recurrence in the mesorectum from a primary ascending colon cancer is a rare finding that has not been previously reported. This may represent a form of retroperitoneal spread, sometimes referred to as "drop metastasis," which is an uncommon mechanism for metachronous recurrence. CASE PRESENTATION: A 38-year-old male presented to the Emergency Department in January of 2018 with profound anemia. A colonoscopy revealed innumerable colonic polyps. He reported having multiple family members diagnosed with colon cancer and was subsequently diagnosed with familial adenomatous polyposis with rectal sparing. Total abdominal colectomy with ileorectal anastomosis was performed, revealing a T3N1a adenocarcinoma of the ascending colon. The patient subsequently underwent 12 cycles of adjuvant FOLFOX. Surveillance imaging in late 2019 revealed a suspicious mass in the superior perirectal soft tissue without any other sites of potential disease. Completion proctectomy was performed in January 2020, 2 years after the initial resection. Pathology revealed a mesorectal tumor deposit located 1.5 cm distal to the ileorectal anastomosis. No evidence of mucosal involvement or nodal metastasis was identified. CONCLUSION: Isolated mesorectal recurrence is a rare and previously unreported clinical finding following resection of an ascending colon cancer with an ileorectal anastomosis. This likely represents a form of retroperitoneal spread.

Vulvar Silicone Granuloma.

We report a case of vulvar silicone granulomas following injection of liquid silicone into the labia. The patient is a 51-yr-old female who presented with vulvar pain and enlarged, indurated labia majora. In the past, she had undergone bilateral labial cosmetic augmentation with a silicone-based filler injected directly into the labia and into the gluteal regions. This had been performed in a nonmedical setting. At surgery, oblong firm soft tissue masses were removed from both labia. Microscopically, the lesions demonstrated replacement of the subcutaneous adipose tissue by fibrous tissue containing innumerable round empty spaces of different sizes, either within or surrounded by macrophages and occasional foreign-body giant histiocytes. The clear vacuoles corresponded to silicone fluid which had been dissolved during tissue processing. There are only rare case reports of vulvar silicone granuloma in the literature, and these were due to migration of silicone to the vulva from distant sites. Our report details a case of vulvar silicone granuloma secondary to direct injection of liquid silicone material into the labia.

Tubulopapillary Carcinoma: An Aggressive Variant of Invasive Breast Carcinoma With a Micropapillary DCIS-Like Morphology.

Tubulopapillary carcinoma is a recently described variant of breast carcinoma characterized by a proliferation of elongated and anastomosing tubular glands exhibiting intraluminal micropapillary and sometimes papillary epithelial projections. We have recently encountered a patient with invasive breast carcinoma displaying a prominent tubulopapillary component. The histomorphology in our case had an uncanny resemblance to micropapillary ductal carcinoma in situ, but the invasive nature of the glands was confirmed not only by the lack of myoepithelial cells but also by the presence of identical metastatic foci within ipsilateral axillary lymph nodes. This case was made all the more intricate by the simultaneous presence of invasive micropapillary carcinoma in the opposite breast and a carcinosarcoma of the uterus with a serous papillary carcinoma component. As noted in the only prior report on tubulopapillary carcinoma of the breast, our case confirms the aggressive nature of this form of invasive carcinoma, the histological features of which appear to be easily identifiable and reproducible.

Pilomatrix carcinoma of the right postauricular region: A case report and literature review.

INTRODUCTION: Pilomatrix carcinoma is a rare aggressive tumor with a high rate of local recurrence after surgical excision. Diagnosis is made by histopathology and when discovered, wide local excision has been shown to have the best results. PRESENTATION OF CASE: We report a case of a 74-year-old male incidentally found to have a large right postauricular mass and regional lymphadenopathy. The mass was biopsied and proven to be a malignant pilomatrixoma. Wide local excision and level II and III neck dissection with reconstruction using a right supraclavicular flap was performed. DISCUSSION: Pilomatrix carcinoma is a lesion first described in 1880 by Malherbe and Chenantais. It is unknown if these tumors arise de novo or arise through malignant transformation of a benign pilomatrixoma. There are similarities between the benign lesion and its malignant counterpart in terms of activating mutations in signaling pathways. A well-defined gold standard for surgical management has not been established, but currently wide local excision with safe margins is recommended along with regional lymph node dissection when metastasis is suspected. Currently, no chemotherapy regimen has been shown to be effective in local control or in preventing metastatic spread. CONCLUSION: Pilomatrix carcinoma, given its aggressive nature, has a high propensity for recurrence after excision. It is important to perform wide local excision to avoid an incomplete resection and higher recurrence rates. Further studies will be needed to create a more defined standard of treatment and to evaluate the role of adjuvant chemotherapy and radiation therapy.

Hepatic Silicone Granulomas Secondary to Ruptured Breast Implants: A Report of Two Cases.

The differential diagnosis of hepatic granulomas is vast and includes infections, drugs, immunologic diseases, foreign material exposure, and neoplasia. Silicone, whether directly injected into tissues or used as a filler in breast implants, is known to cause localized granulomatous reactions. It can also migrate to other anatomic locations resulting in granulomatous inflammation at a distance. We report two cases of unsuspected hepatic silicone granulomas in patients undergoing liver biopsy for isolated elevated alkaline phosphatase levels, both with a history of ruptured breast implants. These cases highlight the need for awareness of hepatic silicone granulomas as an etiology of elevated liver enzymes in patients with a history of surgical interventions utilizing silica, such as cosmetic surgery.

Acute Gastrointestinal Bleeding in Olmesartan-Associated Collagenous Gastroduodenitis: A Potential Endoscopic Complication.

Collagenous gastroenteritis is a rare disease that is known to be associated with the drug olmesartan, an angiotensin II receptor antagonist used to treat hypertension. It is characterized histologically by increased subepithelial collagen deposition with associated inflammation and epithelial injury. Endoscopically, the mucosa appears inflamed and friable and may be nodular or atrophic. We report a case of acute gastric bleeding on direct mucosal contact during endoscopy in a patient with olmesartan-associated collagenous gastroduodenitis to raise awareness of this potential endoscopic complication.

Hepatocellular carcinoma with both fibrolamellar and classical components: an unusual morphological pattern.

Fibrolamellar carcinoma (FLC) is an uncommon form of primary liver malignancy with unique clinical, histological, and biological characteristics. It is usually seen in young adults without underlying liver disease. Histologically, it shows large cells with abundant eosinophilic cytoplasm, large vesicular nuclei, prominent nucleoli, and lamellar type fibrosis. In contrast, classical hepatocellular carcinoma (HCC) is typically present in elderly male patients with cirrhosis. It is the most common histological subtype, and it is characterized by its resemblance to the normal liver, both in its growth pattern and its cytology. The unusual case of a liver carcinoma that presented with histological features of both FLC and classical HCC is herein reported. This was the case of a 37-year-old female complaining of diffuse abdominal discomfort and epigastric pain for two months. She was referred to us for further management after she was diagnosed with HCC in a noncirrhotic liver. She underwent a left-sided hepatectomy. A yellow nodular mass with well-defined borders and a necrotic center was present in the resection specimen. The morphological features and immunohistochemical studies were consistent with a diagnosis of FLC mixed with classical HCC. The patient was followed up for five months, and no signs of recurrence were evident.

Immunohistochemical stains for CD3 and CD8 do not improve detection of gluten-sensitive enteropathy in duodenal biopsies.

Patients with gluten-sensitive enteropathy usually have increased numbers of duodenal intraepithelial lymphocytes even if the villous architecture is normal. Some authors advocate the use of CD8 and CD3 immunohistochemical stains to improve detection of intraepithelial lymphocytosis, yet the added value of immunohistochemistry when biopsies appear normal remains unproven. The purpose of this study was to evaluate the utility of CD3 and CD8 immunostains in detecting intraepithelial lymphocytosis among duodenal biopsies originally interpreted to be normal based on routine evaluation. We identified 200 duodenal biopsies from 172 patients, all of which were accompanied by a clinical question of gluten-sensitive enteropathy. Five well-oriented villi from each biopsy were assessed. Intraepithelial lymphocytes present in hematoxylin and eosin (H&E)-stained slides were counted and compared with the number of CD3 and CD8 immunopositive cells present in the villous epithelium. Results were expressed as the mean number of intraepithelial lymphocytes or immunopositive cells present per 20 villous tip enterocytes. Review of H&E-stained slides revealed a mean of 2.1 ± 0.1 intraepithelial lymphocytes, compared with 3.2 ± 0.1 CD3-positive and 2.1 ± 0.1 CD8-positive intraepithelial cells (P=<0.001 and 1, respectively), although none of the cases displayed sufficient numbers of intraepithelial lymphocytes to be considered abnormal (ie, ≥ 12/20 enterocytes) by any method. The number of intraepithelial lymphocytes detected by H&E evaluation or immunohistochemistry did not correlate with results of serologic studies for markers of gluten sensitivity. We conclude that immunostains for T cell markers do not improve detection of gluten-sensitive enteropathy when H&E-stained sections are normal.

ALK-negative anaplastic large cell lymphoma mimicking a soft tissue sarcoma.

Anaplastic lymphoma kinase protein (ALK)-negative anaplastic large cell lymphoma (ALCL) has a vast morphologic spectrum and may mimic many other types of malignancies both cytologically and histologically. There are only a few published case reports/series describing the cytomorphologic features of ALCL on fine-needle aspiration (FNA) biopsy specimens. We describe a case of ALK-negative ALCL mimicking a high-grade soft tissue sarcoma of the thigh in a 62-year-old man. The characteristic morphologic findings on FNA and core biopsy along with the immunophenotypic profile are described and reviewed. The diagnosis of ALCL on FNA biopsy may be difficult, but can be done successfully with the use of ancillary tests. Therefore, it must be considered in the differential diagnosis of lesions with pleomorphism, anaplasia, and wreath-like or horseshoe-shaped nuclei to ensure that adequate material is obtained for ancillary studies.

Liver biopsies in chronic viral hepatitis: beyond grading and staging.

CONTEXT: Knowledge of the etiology and pathogenesis of chronic viral hepatitis has grown immensely during the past 50 years. The terminology used to assess liver biopsies with chronic viral hepatitis and the role of the liver biopsy itself have also evolved during this time. Although the focus of much discussion regarding diagnostic assessment of liver biopsies in patients with viral hepatitis has been on grading of activity and staging of fibrosis, each biopsy is also an opportunity to assess many other important features. OBJECTIVES: To discuss opportunities provided by biopsies to assess features such as the presence of virus-associated premalignant or malignancy-related changes, and the presence of other concomitant diseases, including fatty liver disease of diverse causes, and hemochromatosis, hereditary or otherwise. DATA SOURCES: The data were obtained from published literature and professional experience. CONCLUSIONS: The evaluation of liver biopsies with chronic viral hepatitis has evolved beyond grading and staging. Pathologists need to be aware of the other features that may have important clinical implications.

A new translocation between chromosomes 6 and 9 helps to establish diagnosis of renal oncocytoma.

Renal oncocytomas are benign epithelial tumors of the kidney. Histologically, they resemble certain malignant renal tumors, such as chromophobe renal cell carcinoma and the eosinophilic or granular form of clear cell renal carcinoma. It is, therefore, important to be able to differentiate among these tumors. Cytogenetic analysis is an important adjunct to the diagnosis of renal tumors, as the various subtypes have specific acquired chromosome abnormalities. Oncocytomas present either with loss of chromosome 1 and a sex chromosome, or with recurring translocations involving chromosome 11. We describe 2 patients with renal oncocytoma and a new translocation between chromosomes 6 and 9. The tumors in both patients were histologically virtually identical. The t(6;9)(p21;p23) may be a new translocation associated with renal oncocytomas.

Clinical and biologic importance of F-actin autoantibodies in HCV monoinfected and HCV-HIV coinfected patients.

The purpose of this study was to evaluate the relationship between serum filamentous (F)-actin antibody titers and severity of hepatitis present in hepatitis C virus (HCV)-infected patients. Liver biopsy samples from 18 HCV monoinfected and 20 HCV-HIV coinfected patients were graded with respect to the degree of hepatitis activity and intensity of plasma cell infiltration using MUM-1 and CD138 immunostains. Of the 38 HCV-infected patients, 6 (16%) had F-actin antibody titers in excess of 30 enzyme-linked immunosorbent assay units. We found a positive trend between serum F-actin antibody levels and the mean number of plasma cells present in the portal tracts of patients with HCV infection (r = 0.31; P = .06) and a significant association between these factors in HCV-HIV coinfected patients (r = 0.64; P = .002). Our data suggest that elevated serum F-actin antibody titers are commonly encountered in HCV-infected patients and may reflect more active inflammation in liver biopsy samples, similar to autoimmune hepatitis.

Diabetic microangiopathy in the liver: an autopsy study of incidence and association with other diabetic complications.

Diabetic hepatosclerosis (DH) is a recently described form of diabetic microangiopathy with hepatic sinusoidal fibrosis and basement membrane deposition without cirrhosis. The objective was to investigate the frequency of DH and its correlation with other diabetic microangiopathic complications. Complete autopsies from 57 adults with diabetes were reviewed for liver pathology and other diabetic complications. Basement membrane deposition in the liver was highlighted using laminin and type IV collagen immunostains. Only 1 case of DH was identified. Other diabetic end-organ damage in this case included nodular glomerulosclerosis and hepatic hyaline arteriolosclerosis, which were the most severe in the series. DH is an uncommon pattern of liver disease in patients with diabetes and is associated with severe end-organ damage. This study supports the presumed vascular etiology of DH, confirms the rarity of the lesion, and supports the suggestion that it is usually accompanied by other end-organ damage.