Paracicatricial melanocytes as a sign of melanoma.

Intradermal melanocytes in the setting of melanoma represent a diagnostic challenge to dermatopathologists as their presence may represent superficially invasive melanoma vs benign nevus cells or reactive dermal melanocytes. Previous dermatologic literature suggests that the absence of cytologic atypia in intradermal melanocytes and their presence in nonmelanocytic neoplasms lends to their characterization as reactive, benign, melanocytic proliferation. A 67-year-old female presented for evaluation of a 10-mm irregularly pigmented dark brown macule on the left cheek. Initial shave biopsy showed transected malignant melanoma measuring at least 0.6 mm in thickness. Multiple reexcision specimens demonstrated residual melanoma with banal appearing intradermal epithelioid melanocytes within and surrounding the scar. The melanocytes tracked into the skin graft, which had previously been free from involvement. Positron emission tomography-computed tomography (PET CT) and lymph node biopsies did not show evidence of metastatic melanoma. Ten months after her diagnosis and following five surgical excisions, the patient was diagnosed with metastatic melanoma to the brain and succumbed to intracranial hemorrhage. We present a case in which paracicatricial melanoma may simulate benign paracicatricial melanocytic hyperplasia. These findings have significant therapeutic and prognostic implications for the practicing dermatologist and dermatopathologist.

Ellipsoid Smooth Muscle Tumor of the Lower Eyelid: An Exploration of Its Possible Origin.

Ocular adnexal smooth muscle masses/neoplasms are extremely rare. Such lesions are comparatively more common in the conjunctiva than in the orbit and are most unusual in the eyelid. A 58-year-old woman slowly developed over 4 months a firm, movable sausage-shaped lesion in the deep lateral half of the right lower eyelid. The lesion ran parallel to and above the orbital rim. At surgery, the lesion was located between the orbicularis muscle and the inferior orbital septum. The term ellipsoid is used descriptively and does not imply any particular biologic behavior. Immunohistochemical evaluation revealed smooth muscle actin and desmin positivity. Due to the ubiquity of small blood vessels and the absence of smooth muscle bundles in the potential space between the orbicularis striated muscle and the inferior orbital septum, venular smooth muscle emerges as a highly likely source for the lesion.

A Lacrimal Gland Choristoma of the Lacrimal Sac.

Choristomatous lacrimal gland tissue has been detected in many different sites of the ocular adnexa, but has never before been convincingly described in the submucosa of the lacrimal sac. A 77-year-old woman with epiphora had a biopsy of the sac wall preformed during a dacryocystorhinostomy that contained such a lacrimal choristoma. Zymogen granules were found in the cytoplasm of the secretory cells with the periodic acid-Schiff reaction. No mucus-producing cells, as found in normal sac submucosal glands, were detected using the Alcian blue, mucicarmine, and Gomori methenamine silver histochemical stains. Gross cystic fluid protein-15 positivity was demonstrated immunohistochemically. The clinical implications of this choristoma are explored.

Limbal Cysts: A Subset Exhibiting Cornea-Specific Cytokeratins.

Two cases of limbal cysts lined by nonkeratinizing epithelium were studied with a panel of cytokeratins. One was a long-standing lesion in a 30-year-old man, whereas the other was excised from a 40-year-old man following pterygium surgery. Each cyst was immunostained with a panel of cytokeratins that were specific exclusively and separately for corneal and conjunctival epithelia. The epithelial lining of each cyst was CK12 positive for corneal epithelium and CK13 negative for conjunctival epithelium. It is hypothesized that a subset of corneoscleral cysts contain corneal epithelium, probably derived from a type of limbal stem cell differentiation.

Dermatofibroma of the Eyelid: Immunohistochemical Diagnosis.

A 66-year-old man developed a painless 2 mm to 3 mm recurrent nodule at the left upper eyelid margin. Excision disclosed a spindle cell lesion without frank atypia or mitotic activity growing in a twisted fascicular pattern often referred to as storiform. All the surgical margins were involved with tumor. Immunohistochemistry demonstrated that many of the constituent spindle and dendritic tumor cells were CD34, factor XIIIa, and CD 163, the latter 2 being biomarkers for monocytic lineage. The lesion was diagnosed as a dermatofibroma rather than a fibrous histiocytoma, a term that should be reserved for more aggressive lesions of deeper fascial planes. Facial dermatofibromas are rarer and more likely than those of the extremities to recur and therefore deserve wider local excision at first surgery with careful and frequent clinical follow ups. Eyelid dermatofibroma has probably often been misdiagnosed as another tumor in the past. Immunohistochemistry can supply valuable biomarker criteria for diagnosis.

Exophytic Osteochondroma of the Brow.

Most bony and cartilaginous lesions of the orbit and periorbital compartments are benign, grow endophytically, and are composed of dense lamellar bone (eburnated or ivory osteomas). An 87-year-old woman had a well-circumscribed, firm, round, and exophytic lesion of the brow region for at least 15 years. Excisional surgery disclosed an osteocartilaginous lesion with an enveloping pseudocapsule (periosteum/perichondrium) and a narrow stalk connecting it to the frontal bone. The periphery of the lesion displayed lamellar bone which appeared to be replacing a central cartilaginous zone. The adjacent deep preaponeurotic fat displayed nodules of collagen with myxoid change and occasional CD34 spindle cells suggestive of a spindle cell lipoma. Because of the osteochondroma's deep location in the preaponeurotic fat, the lesion differs from an osteoma cutis found in the dermis which fails to exhibit a cartilaginous component or a periosteum. Other clinically simulating lesions are described.

Unsuspected Conjunctival Orbital Dermoid Cyst: Aids in Diagnosis.

A 25-year-old man with Type 1 diabetes mellitus experienced rapid visual decline and was scheduled for right cataract surgery. At the time of administering an inferotemporal retrobulbar block, a white discharge appeared spontaneously on the surface of the globe. Superotemporally a cyst was found and its contents were subtotally evacuated. Microscopically, eosinophilic, acellular material with chatter artifact and small vacuoles was detected and initially thought to represent a lens choristoma. This material stained moderately with the periodic acid Schiff method and was focally Congo red positive without apple green birefringence; it also stained blue with the Masson trichrome method. Acid-fast staining disclosed the presence of rare vellous hairs. Adherent cells were not epidermal cells (CK5/6) but conjunctival epithelial cells (CK7); CD68-positive histiocytes were also identified. The lesion was diagnosed as a disrupted orbital dermoid cyst of conjunctival origin.

Eyelid Eccrine Cyst: An Exceptional Lesion Among Dominant Apocrine Cysts.

A 71-year-old woman developed a small bluish lesion beneath the cilia of the left lower eyelid. Excision and microscopic examination disclosed a cyst with an intimately associated eccrine sweat gland. Immunohistochemistry demonstrated that the cyst's epithelium was strongly CK5/6, CK14, CK7 weakly positive, and gross cystic disease fluid protein-15 and smooth muscle actin negative. This is the first immunohistochemically proven eccrine cyst of the eyelid skin. Apocrine cysts develop only at the eyelid margin where the glands of Moll are located. They immunostain positively for cytoplasmic gross cystic disease fluid protein-15 in the adlumenal cells and smooth muscle actin in an outer myoepithelial (abluminal) layer.

Dacryoadenitis as the Initial Presentation of a Natural Killer T-Cell Lymphoma.

Primary orbital natural killer T-cell lymphoma (NKTCL) is a rare condition with only a few published cases in the literature. Over 1 month, an 81-year-old man developed progressive left periocular inflammation unresponsive to treatment. Clinical examination and imaging studies demonstrated a left lacrimal gland enlargement. Bilateral anterior uveitis and erythematous nontender cutaneous lesions were also found. Biopsies of the skin and lacrimal gland on the back revealed histopathologic and immunohistochemical findings confirming Epstein-Barr virus-positive NKTCL. Metastatic work up disclosed multifocal involvement in the pancreas, stomach, and chest wall. Palliative treatment consisting of nonanthracycline-based chemotherapy and radiation was instituted, but the patient died 5 months after the onset of symptoms. This is the first example of acute dacryoadenitis, and the second of bilateral anterior uveitis, in the setting of NKTCL. Absence of naso-sinus involvement in the current case is rare in NKTCL. Despite treatment, the prognosis remains dismal. Orbital specialists should include NKTCL in the differential diagnosis of lacrimal gland/orbital masses and perform an incisional biopsy if the clinical scenario so dictates.

Conjunctival Squamous Cell Neoplasia Associated With Ocular Cicatricial Pemphigoid.

The purpose of this study was to describe a possible causal relationship between ocular cicatricial pemphigoid (OCP) and ocular surface squamous neoplasia. Two middle-aged female patients with already diagnosed OCP were studied in regard to the subsequent onset of conjunctival squamous neoplasia. Their clinical histories, ocular examinations, clinical photographs, and results of biopsies and any ancillary immunofluorescent laboratory evaluation studies were carefully reviewed. One patient had a preinvasive squamous dysplasia and the other an invasive squamous cell carcinoma, both in the unequivocal setting of OCP with bilateral conjunctivitis, symblephara, and forniceal foreshortening. The patients had been receiving intensive immunotherapy consisting of some combination of corticosteroids, rituximab, and interferon alpha. Both patients had a positive immunofluorescent study demonstrating immunoreactants at the level of the epithelial basement membrane. Each patient had 2 earlier negative immunofluorescent studies before a third was positive. While rare, there is 1 previous report of an association between OCP and conjunctival squamous neoplasia. The current report provides more data supporting the proposal that this conjunction is more than a random event. Repeat immunofluorescent studies after an initial negative result in a patient with strong clinical signs of OCP are imperative due to the frequency of false negative studies in the context of clinically persuasive disease.

Does estrogen deficiency cause lacrimal gland inflammation and aqueous-deficient dry eye in mice?

Researchers have proposed that estrogen deficiency will lead to a Sjögren's syndrome (SjS)-like lacrimal gland inflammation, aqueous tear deficiency and dry eye. The purpose of this study was to determine whether this proposal is correct. Lacrimal glands were obtained from adult, age-matched wild type (WT) and aromatase knockout (ArKO) mice, in which estrogen synthesis is completely eliminated. Tissues were also obtained from autoimmune MRL/Mp-lpr/lpr (MRL/lpr) mice as inflammation controls. Tear volumes in WT and ArKO mice were measured and glands were processed for molecular biological and histological evaluation. Our results demonstrate that estrogen absence does not lead to a SjS-like inflammation in lacrimal tissue or to an aqueous-deficient dry eye. There was no upregulation of genes associated with inflammatory pathways in lacrimal glands of male or female ArKO mice. Such inflammatory activity was prominent in autoimmune MRL/lpr tissues. We also found no evidence of inflammation in lacrimal gland tissue sections of estrogen-deficient mice, and tear volumes of ArKO males were actually increased as compared to those WT controls. Interestingly, our study did show that estrogen absence influences the expression of thousands of lacrimal gland genes, and that this impact is sex- and genotype-specific. Our findings demonstrate that estrogen absence is not a risk factor for the development of SjS-like lacrimal gland inflammation or for aqueous-deficient dry eye in mice.

Complex orbital angiomyoma with features of a lymphangiohemangioma.

A 31-year-old woman developed left frontal headache and retrobulbar pain with exotropia and mild limitation of upgaze without proptosis. Imaging studies disclosed a circumscribed mass measuring 1.5 cm in the greatest diameter. At surgery, the lesion was adherent to the surrounding normal orbital tissues, making for a difficult and dangerous resection. Histopathologically and immunohistochemically, the lesion was a mixed cavernous angiomatous (CD31-positive) and lymphangiomatous (D2-40-positive) tumor with abundant interstitial smooth muscle. Such lesions can present significant surgical challenges due to incomplete pseudoencapsulation.

Intraorbital metastasis from solitary fibrous tumor.

Solitary fibrous tumor (SFT) is a rare spindle cell tumor of mesenchymal origin that usually arises from pleura or pericardium but can also arise from many extraserosal sites. Although more than 50 cases of primary SFT of the orbit have been reported, there are no reports to date of a malignant nonophthalmic SFT metastasizing in the orbital soft tissues (although sphenoid wing bony involvement has been reported). The authors report here the first case of a patient with intraorbital metastasis of a CD34-positive malignant SFT. The patient was a 57-year-old man with a history of malignant pleural SFT and a prior kidney metastasis. He presented with the rapid appearance of proptosis and massive conjunctival chemosis preventing eyelid closure, and he was found to have a well-circumscribed metastasis to his lateral rectus muscle. Surgical excision cured his ocular symptoms, although he died 3 months later from brain and widespread metastases.

To Freeze or Not to Freeze? Recommendations for Intraoperative Examination and Gross Prosection of Thyroid Glands.

The use of intraoperative consultation for indeterminate thyroid lesions is not advocated but is still requested by some surgeons. Obscured cytomorphology and nonrepresentative sampling limit the specificity of intraoperative assessment. Formalin fixation of thyroid glands before sectioning also minimizes artifacts introduced by fresh sectioning. Inking of thyroid may vary based on institutional preferences and information desired by clinical teams. Sectioning may occur in the conventional transverse method or the modified transverse vertical method to more thoroughly evaluate the lesion's periphery. Gross examination of thyroid lesions should always consider possible high-grade features, such as necrosis or extrathyroidal extension.

Basaloid follicular hamartoma of the eyelid.

An 86-year-old woman slowly developed a solitary 0.3 3 0.2-cm papule on the left lower eyelid. Complete excision disclosed a honeycombed lesion composed of interlacing basaloid strands unattached to the epidermis but rather extending into the dermis from a dilated hair follicle. The diagnosis was a solitary basaloid follicular hamartoma that can also occur in multiple, generalized, and inherited forms, sometimes with an associated systemic disease. The lesion exhibited a distinctive CD34-positive, mildly cellular myxoid stroma with many CK20-positive Merkel cells scattered within the basaloid cellular strands, which exhibited BCL-2 positivity only within the outermost cells bordering the stroma. These immunohistochemical features are the opposite of those displayed by basal cell carcinomas, which require more aggressive surgical management. Besides basal cell carcinomas, the differential diagnosis of basaloid follicular hamartoma includes fibrofolliculoma, tumor of the follicular infundibulum, poroma, and trabecular (Merkel cell) carcinoma.

Bacterial and mucopeptide concretions of the lacrimal drainage system: an analysis of 30 cases.

PURPOSE: To demonstrate the histopathologic characteristics of different types of lacrimal drainage system concretions with clinical correlations. METHODS: Thirty lacrimal drainage system concretions submitted to the Cogan Eye Pathology Laboratory at the Massachusetts Eye and Ear Infirmary over a 2-year period were reviewed. Concretions were studied in detail using their histopathologic staining features as revealed with hematoxylin and eosin, Gomori methenamine silver, periodic acid-Schiff, iron stain, and Brown-Hopps tissue gram stain. A separate retrospective chart review was conducted for each patient to identify any clinical correlations. RESULTS: Two major forms of concretions were identified histopathologically: mucopeptide (7) and bacterial (20). Mucopeptide concretions were found exclusively within the lacrimal sac, while bacterial concretions were found chiefly in the canaliculus. A third category of "mixed" concretions with substantial mucopeptide and bacterial characteristics comprised 3 specimens. Bacterial concretions consisted of large matted masses of filamentous, presumed Actinomyces organisms that were easily identified with the Grocott's methenamine silver stain; they were frequently cocolonized at their edges with coccal bacterial forms. Mucopeptide concretions were generally devoid of cellular elements and were composed of broad bland whorls of diffusely eosinophilic, acellular, periodic acid-Schiff-positive material punctuated by lacunae. They were often cocolonized by small numbers of bacterial cocci and occasional fungi. Culture results disclosed low virulence species. All 3 types of concretions predominated in women. Patients with bacterial concretions frequently had dry eye symptoms. CONCLUSIONS: The 2 major types of lacrimal system concretions differ in their primary location and histopathologic composition. Further characterization may lead to an understanding of the mechanisms for their formation. Mucopeptide concretion is more appropriate than terms such as "dacryolith" and "mucolith," and bacterial concretion is a more appropriate term than "canaliculith," because of the absence of significant calcium or stone-like density in these masses.

Angiomyofibroma of the orbit: a hybrid of vascular leiomyoma and cavernous hemangioma.

PURPOSE: The aim of this study was to describe a novel primary orbital vascular tumor combining elements of a vascular leiomyoma (angioleiomyoma) and a cavernous hemangioma. METHODS: A critical review of clinical records, diagnostic tests, and radiographic studies combined with histopathologic evaluation with standard and special histochemical staining and immunohistochemical investigations was conducted. RESULTS: A 44-year-old man slowly developed 5 mm of well-tolerated relative right proptosis with minimal motility disturbance and no visual decline. Computed tomography and magnetic resonance imaging demonstrated a medial and intraconal rounded mass that perfused slowly and whose anterior surface was well circumscribed. At surgery, the tumor was solid and pink with intersecting white bands and densely attached to surrounding normal tissues. The most adherent apical portion of the mass was left behind after subtotal excision. Histopathologically, only a partial pseudocapsule was discovered. The tumor was composed of cavernous channels, capillary zones, compressed lumens with linear strands of endothelium, and collections of muscular veins devoid of an elastica. Striking smooth muscle actin positivity was identified in disorganized masses of smooth muscle cells in the intervascular spaces and around the cavernous vascular units; these myocytes were intermixed with bundles of interstitial keloidal collagen. The endothelium was CD31 and CD34 positive for vascular endothelium and D2-40 negative for lymphatic endothelium. CONCLUSIONS: The authors have classified this hybrid tumor an angiomyofibroma with low neoplastic potential and features of a malformation. It is a composite variant of cavernous hemangioma associated with a conspicuous proliferation of anomalous disorganized smooth muscle cells (leiomyoma). Most of the lesion lacked a pseudocapsule, which impeded surgical delivery. Incomplete excision is recommended in such cases as preferable to the complications that could ensue from overly aggressive efforts at complete removal, particularly at the orbital apex. Supporting this position is the observation that incompletely excised cavernous hemangioma generally does not recur.

Isolated unilateral linear epidermal nevus of the upper eyelid.

A 75-year-old man presented with a recurrent, unilateral, solitary, linear, corrugated lesion of the right upper eyelid of prolonged duration together with bilateral dermatochalasis. A re-excision with blepharoplasty was performed. Histopathologic analysis of the tissue revealed parallel linear arrays of papillomatosis and acanthosis with overlying basket-weave hyperkeratosis consistent with a linear epidermal nevus. Immunohistochemical studies disclosed normal numbers of intraepidermal melanocytes and Langerhans cells without Merkel cells or an increase in cycling keratinocytes. Although the term "nevus" is mostly used in conjunction with the common nevomelanocytic nevus, in fact nevi of other cutaneous cellular elements can occur on a malformational basis (such as sebaceous, eccrine, apocrine, pilar, and elastic fiber nevi). Ophthalmologists should be aware of epidermal nevi because they are rarely associated with cataracts, malignant cutaneous neoplasms, neurologic abnormalities, and musculoskeletal disorders. For focal lesions like the present one, local excision is appropriate. A select differential diagnosis of histopathologically related conditions is provided.

Orbital perineurioma in the setting of dacryocystitis.

A benign orbital perineurioma was discovered just posterior to the lacrimal sac during surgery for recurrent bacterial dacryocystitis in an 83-year-old woman. The tumor was circumscribed but nonencapsulated and located exterior to the lacrimal sac mucosa. It was composed of cytologically bland spindle cells organized in graceful, elongated, and twisted bundles reminiscent of a storiform pattern. Immunohistochemical staining displayed a diagnostic pattern of Claudin-1, GLUT-1, and epithelial membrane antigen positivity. Malignant transformation is virtually unknown, even with incomplete excision. The differential diagnosis includes neurofibroma, schwannoma, leiomyoma, solitary fibrous tumor (CD34 positive), and low-grade fibromyxoid sarcoma.

Characteristics of Pelvic Cytology in Patients with Gynecologic Malignancies: Comparison of Pre and Post-Neoadjuvant Specimens.

INTRODUCTION: The presence of tumor cells in pelvic cytology (PC) specimens can portend a worse outcome for patients undergoing gynecologic surgery. Primary debulking surgery (PDS) was a mainstay for most of these tumors; however, recent advances have triaged selected patients to neoadjuvant chemotherapy (NACT) with interval debulking surgery (IDS). Reduction in tumor cellularity and histologic alterations has been noted in these cases; however, similar cytologic characterization has not been performed. MATERIALS AND METHODS: PC was searched to find those in NACT patients. Additional PDS were included as controls. Cases were scored for cellularity of malignant cells and background components were described, and when available, pretreatment and posttreatment specimens from the same patients were compared. RESULTS: In all, 19 specimens from 16 patients were found, 6 (32%) of which were paired PTS and IDS from the same patient. Only 6/19 (32%) were from IDS, the remainder PTS. A majority (15/19; 79%) of specimens were malignant; all negative cases were PTS. Few (4/16; 24%) were endometrial primaries; the remainder were pelvic high-grade serous carcinoma. No difference in tumor cell morphology or inflammatory component was noted between the 2 groups, though in 3/3 paired specimens from PDS and IDS, the cellularity of malignant cells decreased in the IDS specimens. DISCUSSION/CONCLUSION: No identifiable trend was noted regarding cellularity of specimens in the pre compared to the post-neoadjuvant setting. A trend toward reduced cellularity was noted in individual patients, but no alteration in background cells or tumor morphology was noted.