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Basal cell carcinoma presenting as a large pore
Basal cell carcinoma presenting as a large pore Anthony V. Benedetto, DO, FACP, Ernest A. Benedetto, MD, and Thomas D. Griffin, MD Philadelphia, Pennsylvania Background: Certain facial lesions clinically appear as large pores, and when examined microscopically, they are found to be basal cell carcinomas (BCCs). Objectives: The purposes of this study were to determine the clinical and histologic characteristics of certain large-pore facial lesions, which, on microscopic examination, are found to be BCCs and to identify, if any, a clinical profile of the patients who might be prone to development of such large-pore BCCs. Methods: Microscopic examination of biopsy tissue, obtained from patients who presented clinically with characteristic large-pore lesions of the face during the years 1988 to 2000, was performed. Results: Eleven biopsy specimens from 10 patients who presented with long-standing, gaping pores in the center of the face were shown to be BCCs with features of follicular differentiation and focal keratinization. These patients also had thick, sebaceous skin, and most were users of tobacco. Conclusion: Enlarged pores or pits in the center of the face, present for a long period in patients with thick sebaceous skin, should be examined for evidence of BCC. These large-pore lesions may be BCCs with histologic features of follicular differentiation. (J Am Acad Dermatol 2002;47:727-32.)
M
ost basal cell carcinomas (BCCs) have a particular clinical appearance, which can correlate somewhat with their histologic features. For example, a BCC that clinically presents as a scaly, plaque-like lesion is usually found to be a superficial multicentric BCC on histologic examination. A BCC that clinically presents as an atrophic or scar-like lesion may appear as a morpheaform BCC under the microscope. However, nodular BCCs may manifest different histologic patterns.1-3 In this report, we present a not easily identified, unusual clinical form of BCC that appears as a slowly enlarging, dilated pore in the center of the face. On histologic examination, this lesion was found to be a nodular BCC, manifesting evidence of follicular differentiation.
METHODS This is a retrospective study of patients who presented between 1988 and 2000 at our Ambulatory From MCP Hahnemann School of Medicine. Funding sources: None. Conflict of interest: None. Presented at the annual meeting of the American Academy of Mohs Micrographic Surgery & Cutaneous Oncology, Boston, Mass, May 4-7, 1997. Accepted for publication April 24, 2001. Reprint requests: Anthony V. Benedetto, DO, FACP, 1200 Locust St, Philadelphia, PA 19107. Copyright © 2002 by the American Academy of Dermatology, Inc. 0190-9622/2002/$35.00 ⫹ 0 16/1/124075 doi:10.1067/mjd.2002.124075
SurgiCenters with large-pore lesions on the face, which were diagnosed as BCCs on microscopic examination. Each patient’s sex, age, and skin type were recorded, along with the location and time of initial appearance of the large-pore lesion. The patient’s history of previous premalignant and malignant lesions was documented, as well as whether he or she smoked tobacco. Patients were examined for the presence or absence of solar elastosis and premalignant or other malignant skin lesions on the face and body. Ten patients, 7 men and 3 women, had lesions that appeared as small, gaping pores, which for many years had been slowly enlarging in the center of their faces. One patient (patient 5) had two separate and clinically distinct large-pore lesions, one on the tip of and the other on the right side of his nose. Biopsy specimens of all 11 lesions were obtained from the 10 patients and evaluated. All biopsy specimens were fixed in buffered formalin and stained with hematoxylin and eosin. Slides were reviewed by a board-certified dermatopathologist (T. D. G.). Histopathologic features that were evaluated included the presence or absence of the following: subtype of BCC; anatomic site of origin (epidermis or follicle); pattern of invasion (nodular or infiltrative); circumscription of tumor cells; follicular plugging; follicular differentiation identified by the formation of papillary mesenchymal bodies, follicular buds, or keratin cysts; peripheral retraction spaces around tumor lobules; type of stroma around tumor lobules; squamous differentiation (keratin 727
728 Benedetto, Benedetto, and Griffin
J AM ACAD DERMATOL NOVEMBER 2002
Table I. Clinical profile of patients diagnosed with large-pore BCC Patient No.
Sex/Age (y)
Location
Fitzpatrick skin type
Length of time present before diagnosis
1 2
M/59 R nasolabial sulcus M/53 L lower m-l sulcus
III II
Many years 25⫹ y
10/88 9/93
3 4 5
II II III
6 7
M/55 R upper m-l sulcus M/45 R upper lip M/64 Nasal tip R side of nose M/76 R side of nose F/80 L lower forehead
III III
30⫹ y 10⫹ y 10⫹ y Many years Many years Many years
7/96 11/96 11/96/ 11/96 2/97 10/97
8
M/71 L lower m-l sulcus
III
Many years
10/99
F/68 Nasal bridge F/82 Nose
III I
1-2 y 1⫹ y; changed and became more nodular
8/00 10/00
9 10
Type & No. of other cancers
Hx of tobacco use
Years of follow-up without recurrence
⫹/⫹ BCC ⫻2 ⫹/⫹ BCC ⫻6 SCC ⫻1 ⫹/⫺ None ⫹/⫹ BCC ⫻15 ⫹/⫹ BCC ⫻3
Yes Yes
12.5 7.5
No Yes Yes
⫹/⫹ SCC ⫻2 ⫹/⫹ BCC ⫻2 SCC ⫻9 multiple myeloma ⫹/⫹ BCC ⫻22 SCC ⫻2 ⫹/⫹ BCC ⫻1 ⫹/⫹ None
Yes Yes
4.5 4.5 4.5 4.5 4.0 3.5
Yes
1.5
Yes Yes
1.0 0.5
Month/year SE/AK treated No.
AK, Actinic keratoses; BCC, basal cell carcinoma; Hx, history; L, left; m-l, melolabial; R, right; SCC, squamous cell carcinoma; SE, solar elastosis; ⫹, present; ⫺, absent.
pearl formation); calcification; and skeletal muscle invasion. After diagnostic confirmation, all but one (patient 10) of the BCCs were treated by means of freshtissue Mohs micrographic surgery performed by one of us (A. V. B. or E. A. B.).
RESULTS The clinical characteristics of the patients with large-pore BCCs can be found in Table I. There were 7 men and 3 women, ranging in age from 45 to 82 years, with a mean age of 65 years. All the lesions appeared in the center of the face, and most were present for many years. All patients exhibited clinical evidence of solar elastosis and most (except patient 3) had a history of actinic keratoses. All were smokers of tobacco, except one (patient 3), and all had Fitzpatrick skin type I, II, or III. All patients except two (patients 3 and 10) had a history of prior skin cancers (ie, BCC or squamous cell carcinoma), and one (patient 7) also had a history of multiple myeloma. None of the patients in the 12 years of follow-up (mean, 4.85 years) have ever had a recurrence of any of their skin cancers after fresh-tissue Mohs micrographic surgery. Biopsy specimens from the 10 patients and 11 lesions all manifested a similar histologic pattern of BCC, the results of which are listed in Table II. In the 11 lesions examined microscopically, tumor cells arose either primarily or focally from follicular epithelium or from a centrally located follicular ostium
that contained keratin (Fig 1, A). Basaloid tumor cells were also observed to arise focally from the epidermis of what appeared to be vellus hair follicles. Five of the 11 lesions were poorly circumscribed, and 4 of them were found to invade skeletal muscle. Most showed a lobular growth pattern. Tumor cells were arranged in cords and small lobules, which contained follicular buds and structures resembling papillary mesenchymal bodies (Fig 1, B). Keratin cysts, either small or large, were seen in 9 of 11 lesions. The stroma was generally cellular and closely approximated to the tumor. Retraction spaces and mucin were not prominent. Amyloid was present in the stroma of one patient (patient 7) who had had multiple myeloma for 6 years before biopsy. Squamous differentiation was seen in one case (patient 4). Overall, the features of all 11 large-pore lesions revealed a nodular BCC exhibiting a tendency toward follicular differentiation.
DISCUSSION We all have seen patients with thick sebaceous skin who have dilated, gaping pores, especially in the center of the face. Many of these enlarged, patulous pores can be identified clinically and histologically as sebaceous hyperplasia, solar comedones of Favre and Racouchot, dilated pores of Winer, pilar sheath acanthomas,4 dilated openings of follicular cysts, or old scars from acne, varicella, or trauma. However, there is a peculiar type of lesion that occurs in the center of the face and appears as a
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Table II. Histopathologic characteristics of a large pore BCC
Patient No.
1 2 3 4 5 6 7 8 9 10
Subtype
NF NF NF NF NF* NF† NF NF NF NF NF
Anatomic Pattern site of of Skeletal Squamous origin invasion muscle Follicular Circum- Follicular Keratin Cellular Retraction differen(E or F) (N or I) invasion plug scription buds cysts stroma spaces tiation Calcification
⫺⫹ ⫹⫹ ⫺⫹ ⫹⫹ ⫺⫹ ⫺⫹ ⫺⫹ ⫺⫹ ⫹⫹ ⫹⫹ ⫺⫹
N N N N N N I N N N N
⫹ ⫹ ⫺ ⫹ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺
⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹
⫺ ⫺ ⫹ ⫺ ⫺ ⫹ ⫺ ⫹ ⫹ ⫹ ⫹
⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹
⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺
⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹‡ ⫺ ⫺ ⫺
⫺ ⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺
⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺
⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺
E, Epidermal; F, follicular; I, infiltrative; N, nodular; NF, nodular with follicular differentiation; ⫹, present; ⫺, absent. *Nasal tip. † Right side of nose. ‡ Amyloid present.
slowly enlarging, gaping pore with or without central keratinaceous debris, which escapes detection as a BCC (Fig 2). Because lesions of this type do not resemble or act like any other BCC, their identification can be overlooked even by the most experienced physician. We believe that many of these lesions can begin as a cluster of small pores with central plugging (Fig 3), which in time develop into a single patulous stellate pit or pore with or without a central keratinaceous plug (Fig 2). Eventually, these lesions may develop a collarette of slightly indurated, yellow-colored and wax-like textured skin that forms the ridged shoulders of the pore ostium, which usually contains keratinaceous debris in its center (Figs 4 and 5). Patients who have had many BCCs treated over a long period may doubt that these lesions are BCCs. They may even resist biopsy and treatment, because the large-pore BCC can be present for many years, demonstrating virtually no change or growth. In our experience, 3 patients with histories of multiple skin cancers initially refused a biopsy of their large-pore BCCs. One patient (patient 2) was followed up for 6 years before consenting to a biopsy (Fig 4); another (patient 4), for 6 months (Fig 5); and the third (patient 6), for 4 months. Also, another two of the large-pore BCCs were identified only after they were excised. Before surgery, they were thought to be epidermoid cysts (Fig 3). However, after routine microscopic examination, they were found to be BCCs with follicular differentiation. Table III summarizes the 12 clinical features frequently observed in the 10 patients who had, in the center of their faces, a BCC that appeared as a large pore.
Fig 1. Biopsy specimen (from patient 10) shows a central follicle with a dilated follicular orifice from which nests and lobules of basaloid cells emanate (A). A closer view shows lobules of cytologically atypical basaloid cells forming small buds with peripheral palisading, absence of retraction spaces, and a cellular stroma (B). (A and B, Hematoxylin-eosin stain; original magnifications: A, ⫻10; B, ⫻20.)
730 Benedetto, Benedetto, and Griffin
Fig 2. Patient 5 had, for many years, a typical stellate pit that was a large-pore BCC on the dorsal tip of his nose, measuring less than 5 mm in diameter (arrow).
Fig 3. Right lateral view of patient 5, 1 month after Mohs micrographic surgery done for the large-pore BCC on the tip of his nose. A second large-pore BCC can be seen on the right side of his nose, presenting as a cluster of plugged pores measuring less than 5 mm in overall diameter (arrow). This second large-pore BCC, which was present for a shorter period, was mistaken for an epidermoid cyst. Its true identity was discovered only after surgery, when the pathology report revealed a BCC.
Even though mention of the clinical existence of large-pore BCCs can be found in the current literature,5,6 an exact reference to these lesions could not be identified (R. A. Schwartz, MD, telephone communication, February 1999). However, there ap-
J AM ACAD DERMATOL NOVEMBER 2002
pears to be a correlation between the characteristic clinical presentation of the large-pore BCC and its histopathologic structure. Carlson-Sweet et al7 recently made reference to a trichoid BCC found in a dilated pore on the nose but identified the BCC as appearing within a dilated pore of Winer. Routine microscopic examination of skin biopsy specimens from the 10 patients with 11 large-pore lesions all revealed a BCC with some degree of follicular differentiation. The criteria used to identify follicular differentiation included the presence of small and large keratin cysts lined by cornified cells, resembling follicular epithelium, and cords or buds of basaloid cells, forming structures reminiscent of follicular bulbs or papillary mesenchymal bodies. In addition, retraction spaces were absent in most cases, and the stroma was cellular. Of particular interest was the histologic presence of either a follicular plug within the BCC or tumor cells arising from follicular ostia in the superficial portion of the BCC. This correlated well with the clinical presentation of the original large-pore lesion, whether it was a lesion with one large central pore or one with a clustered group of small pores (Figs 2, 3, and 4). In some cases, only a small remnant of the follicle was seen, whereas in others, tumor cells were clearly emanating from a central follicular structure. This was interpreted as being partly due to the method by which the original diagnostic biopsy specimens were obtained. Full-thickness punch biopsy specimens encompassed the entire central core of the lesion, providing a more complete view of the overall structure of these large-pore BCCs. In shave biopsies, on the other hand, only small superficial portions of the lesion were removed, providing an incomplete view of the overall structure of the large-pore BCC. The histologic differential diagnosis of a largepore BCC includes various types of adnexal tumors showing follicular differentiation. However, most, if not all, of them usually appear clinically as nodular lesions. Most prominent among these would be trichofolliculoma, trichoepithelioma, and trichoblastoma.8 Clinically, a trichofolliculoma commonly appears as a nodular lesion. On histologic examination, well-differentiated, hair-producing secondary hair follicles are seen arising from a central follicular orifice, which contains multiple vellus hairs emanating from it. In large-pore BCC, buds of atypical basaloid cells do not form well-differentiated follicles. A trichoepithelioma usually presents clinically as a well-circumscribed nodular lesion. On histologic examination, well-circumscribed lobules of basaloid cells forming small cysts and papillary mesenchymal bodies are frequently seen in the upper dermis. The stroma is cellular, closely approximated to the tumor
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Benedetto, Benedetto, and Griffin 731
Fig 4. Patient 2 had a typical large-pore BCC of the left lower melolabial sulcus present since early adulthood. A BCC (arrow) was clinically diagnosed in September 1987 (A), but the patient refused a biopsy or treatment. Same lesion (arrow) as it appeared in 1989 (B) and then in September 1993 (C) before biopsy and Mohs micrographic surgery (arrow). Same lesion (arrow) in September 1993 (D) with the cheek retracted laterally, revealing the full extent of the patulous pore with its characteristic stellate appearance and yellow, wax-like skin surface changes.
cells, and generally lacks mucin and peripheral retraction spaces. In both large-pore BCC and trichoepithelioma, the stroma is compressed and cellular and lacks peripheral retraction spaces and mucin. Papillary mesenchymal bodies are present but are not as numerous in large-pore BCCs as they usually
are in trichoepitheliomas. Although large-pore BCCs demonstrate a tendency toward follicular differentiation, their basaloid cells show cytologic atypia and are much less well differentiated than the basaloid cells comprising trichoepitheliomas. Appearing as nodules on the skin, some forms of
732 Benedetto, Benedetto, and Griffin
Fig 5. Patient 4 had at least 15 other BCCs over his face, trunk, and extremities but refused to acknowledge that this lesion on the right side of the upper lip was a BCC. This long-standing large-pore BCC is seen as a patulous stellate pore with a collarette of wax-like skin surface changes (arrow). The pore ostium is devoid of hair and contains keratinaceous debris.
Table III. Twelve clinical features of a large-pore BCC 1. A stellate pit or a cluster of gaping pores 1-5 mm in diameter with or without central keratinaceous debris 2. Older lesions have slightly perceptible or no induration, and their ostia become more patulous with time, acquiring a yellow, wax-like texture 3. Flush with the surrounding, normal-appearing skin 4. No friable, rolled edges, but acutely angled, asymmetrically ridged shoulders surrounding the ostium of the pore 5. No gray, pearly, translucent tissue 6. No telangiectasia 7. No bleeding or crusting 8. Located in the center of the face 9. In men and women with thick sebaceous skin 10. In smokers of tobacco 11. Very slow growing with minimal to no change 12. Present for many years
trichoblastoma can be difficult to distinguish from BCC.9 On histologic examination, trichoblastomas are generally well-circumscribed nodules of basaloid cells, which, unlike trichoepithelioma, are located in the mid to lower dermis or subcutaneous tissue.10 A superficial variant of trichoblastoma has been described, mostly in association with nevus sebaceus of Jadassohn.11 In these lesions, areas of sebaceous differentiation can be found. Different forms of trichoblastoma have been described, depending on the prominence of the stroma present.8
J AM ACAD DERMATOL NOVEMBER 2002
Tumor cells in a trichoblastoma usually do not arise from preexisting follicular epithelium, as they do in large-pore BCC. Moreover, a large-pore BCC does not have the same type of prominent stroma as seen in trichoblastoma. A recent report suggests a genetic abnormality common to sporadic trichoepithelioma and BCC.12 Deletions at the chromosome locus 9q22.3, which is in the patched gene locus, were seen in 48% of sporadic trichoepitheliomas. This incidence is similar to that of BCC and suggests a common pathway for these lesions. Therefore, it is not surprising that variants of BCC exist, manifesting some form of follicular differentiation, such as those found in a large-pore BCC. In conclusion, all physicians who treat patients in whom skin cancer may develop need to be aware of BCCs presenting as a large pore in the center of the face. On histologic examination, these large-pore BCCs usually manifest some degree of follicular differentiation. We thank Kathleen Kucer, MD, for permission to include one of her patients (patient 10) in this report. REFERENCES 1. Elder D, Elenitsas R, Jaworsky C, Johnson B. Lever’s histopathology of the skin. 8th ed. Philadelphia: JB Lippincott; 1997. p. 729. 2. Sexton M, Jones DB, Maloney ME. Histologic pattern analysis of basal cell carcinoma: study of a series of 1039 consecutive neoplasms. J Am Acad Dermatol 1990;23:1118-26. 3. Emmett AJJ. Surgical analysis and biologic behavior of 2277 basal cell carcinomas. Aust N Z J Surg 1990;60:855-63. 4. Klovekorn G, Klovekorn W, Plewig G, Pinkus H. Giant pore and hair shaft acanthoma, clinical and histopathologic diagnosis. Hautarzt 1983;34:209-16. 5. Schwartz RA. Skin cancer: recognition and management. New York: Springer-Verlag; 1988. p. 57-70. 6. Andrade R, Gumport SL, Popkin GL, Rees TD. Basal cell epithelioma. In: Andrade R, editor. Cancer of the skin: biology-diagnosis-management. Vol 2. Philadelphia: WB Saunders Co; 1976. p. 821-44. 7. Carlson-Sweet KL, Weigand DA, MacFarlane DF. Trichoid basal cell carcinoma found in a dilated pore on the nose. Dermatol Surg 2000;26:874-6. 8. Headington JT. Tumors of the hair follicle: a review. Am J Pathol 1976;85:479-514. 9. Ackerman AB, DeViragh PA, Chongchitnant N. Trichoblastoma. In: Neoplasms with follicular differentiation. Philadelphia: Lee & Febiger; 1993. p. 606-59. 10. Graham BS, Barr RJ. Rippled-pattern sebaceous trichoblastoma. J Cutan Pathol 2000;27:455-9. 11. Kaddu S, Soyer HP, Kerl H. Trichoblastoma arising in nevus sebaceous [abstract]. Am J Dermatopathol 1997;19:429. 12. Matt D, Xin H, Vortmeyer A, Zhuang Z, Burg G, Boni R. Sporadic trichoepithelioma demonstrates deletions at 9q22.3. Arch Dermatol 2000;136:657-60.
M
ost basal cell carcinomas (BCCs) have a particular clinical appearance, which can correlate somewhat with their histologic features. For example, a BCC that clinically presents as a scaly, plaque-like lesion is usually found to be a superficial multicentric BCC on histologic examination. A BCC that clinically presents as an atrophic or scar-like lesion may appear as a morpheaform BCC under the microscope. However, nodular BCCs may manifest different histologic patterns.1-3 In this report, we present a not easily identified, unusual clinical form of BCC that appears as a slowly enlarging, dilated pore in the center of the face. On histologic examination, this lesion was found to be a nodular BCC, manifesting evidence of follicular differentiation.
METHODS This is a retrospective study of patients who presented between 1988 and 2000 at our Ambulatory From MCP Hahnemann School of Medicine. Funding sources: None. Conflict of interest: None. Presented at the annual meeting of the American Academy of Mohs Micrographic Surgery & Cutaneous Oncology, Boston, Mass, May 4-7, 1997. Accepted for publication April 24, 2001. Reprint requests: Anthony V. Benedetto, DO, FACP, 1200 Locust St, Philadelphia, PA 19107. Copyright © 2002 by the American Academy of Dermatology, Inc. 0190-9622/2002/$35.00 ⫹ 0 16/1/124075 doi:10.1067/mjd.2002.124075
SurgiCenters with large-pore lesions on the face, which were diagnosed as BCCs on microscopic examination. Each patient’s sex, age, and skin type were recorded, along with the location and time of initial appearance of the large-pore lesion. The patient’s history of previous premalignant and malignant lesions was documented, as well as whether he or she smoked tobacco. Patients were examined for the presence or absence of solar elastosis and premalignant or other malignant skin lesions on the face and body. Ten patients, 7 men and 3 women, had lesions that appeared as small, gaping pores, which for many years had been slowly enlarging in the center of their faces. One patient (patient 5) had two separate and clinically distinct large-pore lesions, one on the tip of and the other on the right side of his nose. Biopsy specimens of all 11 lesions were obtained from the 10 patients and evaluated. All biopsy specimens were fixed in buffered formalin and stained with hematoxylin and eosin. Slides were reviewed by a board-certified dermatopathologist (T. D. G.). Histopathologic features that were evaluated included the presence or absence of the following: subtype of BCC; anatomic site of origin (epidermis or follicle); pattern of invasion (nodular or infiltrative); circumscription of tumor cells; follicular plugging; follicular differentiation identified by the formation of papillary mesenchymal bodies, follicular buds, or keratin cysts; peripheral retraction spaces around tumor lobules; type of stroma around tumor lobules; squamous differentiation (keratin 727
728 Benedetto, Benedetto, and Griffin
J AM ACAD DERMATOL NOVEMBER 2002
Table I. Clinical profile of patients diagnosed with large-pore BCC Patient No.
Sex/Age (y)
Location
Fitzpatrick skin type
Length of time present before diagnosis
1 2
M/59 R nasolabial sulcus M/53 L lower m-l sulcus
III II
Many years 25⫹ y
10/88 9/93
3 4 5
II II III
6 7
M/55 R upper m-l sulcus M/45 R upper lip M/64 Nasal tip R side of nose M/76 R side of nose F/80 L lower forehead
III III
30⫹ y 10⫹ y 10⫹ y Many years Many years Many years
7/96 11/96 11/96/ 11/96 2/97 10/97
8
M/71 L lower m-l sulcus
III
Many years
10/99
F/68 Nasal bridge F/82 Nose
III I
1-2 y 1⫹ y; changed and became more nodular
8/00 10/00
9 10
Type & No. of other cancers
Hx of tobacco use
Years of follow-up without recurrence
⫹/⫹ BCC ⫻2 ⫹/⫹ BCC ⫻6 SCC ⫻1 ⫹/⫺ None ⫹/⫹ BCC ⫻15 ⫹/⫹ BCC ⫻3
Yes Yes
12.5 7.5
No Yes Yes
⫹/⫹ SCC ⫻2 ⫹/⫹ BCC ⫻2 SCC ⫻9 multiple myeloma ⫹/⫹ BCC ⫻22 SCC ⫻2 ⫹/⫹ BCC ⫻1 ⫹/⫹ None
Yes Yes
4.5 4.5 4.5 4.5 4.0 3.5
Yes
1.5
Yes Yes
1.0 0.5
Month/year SE/AK treated No.
AK, Actinic keratoses; BCC, basal cell carcinoma; Hx, history; L, left; m-l, melolabial; R, right; SCC, squamous cell carcinoma; SE, solar elastosis; ⫹, present; ⫺, absent.
pearl formation); calcification; and skeletal muscle invasion. After diagnostic confirmation, all but one (patient 10) of the BCCs were treated by means of freshtissue Mohs micrographic surgery performed by one of us (A. V. B. or E. A. B.).
RESULTS The clinical characteristics of the patients with large-pore BCCs can be found in Table I. There were 7 men and 3 women, ranging in age from 45 to 82 years, with a mean age of 65 years. All the lesions appeared in the center of the face, and most were present for many years. All patients exhibited clinical evidence of solar elastosis and most (except patient 3) had a history of actinic keratoses. All were smokers of tobacco, except one (patient 3), and all had Fitzpatrick skin type I, II, or III. All patients except two (patients 3 and 10) had a history of prior skin cancers (ie, BCC or squamous cell carcinoma), and one (patient 7) also had a history of multiple myeloma. None of the patients in the 12 years of follow-up (mean, 4.85 years) have ever had a recurrence of any of their skin cancers after fresh-tissue Mohs micrographic surgery. Biopsy specimens from the 10 patients and 11 lesions all manifested a similar histologic pattern of BCC, the results of which are listed in Table II. In the 11 lesions examined microscopically, tumor cells arose either primarily or focally from follicular epithelium or from a centrally located follicular ostium
that contained keratin (Fig 1, A). Basaloid tumor cells were also observed to arise focally from the epidermis of what appeared to be vellus hair follicles. Five of the 11 lesions were poorly circumscribed, and 4 of them were found to invade skeletal muscle. Most showed a lobular growth pattern. Tumor cells were arranged in cords and small lobules, which contained follicular buds and structures resembling papillary mesenchymal bodies (Fig 1, B). Keratin cysts, either small or large, were seen in 9 of 11 lesions. The stroma was generally cellular and closely approximated to the tumor. Retraction spaces and mucin were not prominent. Amyloid was present in the stroma of one patient (patient 7) who had had multiple myeloma for 6 years before biopsy. Squamous differentiation was seen in one case (patient 4). Overall, the features of all 11 large-pore lesions revealed a nodular BCC exhibiting a tendency toward follicular differentiation.
DISCUSSION We all have seen patients with thick sebaceous skin who have dilated, gaping pores, especially in the center of the face. Many of these enlarged, patulous pores can be identified clinically and histologically as sebaceous hyperplasia, solar comedones of Favre and Racouchot, dilated pores of Winer, pilar sheath acanthomas,4 dilated openings of follicular cysts, or old scars from acne, varicella, or trauma. However, there is a peculiar type of lesion that occurs in the center of the face and appears as a
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Table II. Histopathologic characteristics of a large pore BCC
Patient No.
1 2 3 4 5 6 7 8 9 10
Subtype
NF NF NF NF NF* NF† NF NF NF NF NF
Anatomic Pattern site of of Skeletal Squamous origin invasion muscle Follicular Circum- Follicular Keratin Cellular Retraction differen(E or F) (N or I) invasion plug scription buds cysts stroma spaces tiation Calcification
⫺⫹ ⫹⫹ ⫺⫹ ⫹⫹ ⫺⫹ ⫺⫹ ⫺⫹ ⫺⫹ ⫹⫹ ⫹⫹ ⫺⫹
N N N N N N I N N N N
⫹ ⫹ ⫺ ⫹ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺
⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹
⫺ ⫺ ⫹ ⫺ ⫺ ⫹ ⫺ ⫹ ⫹ ⫹ ⫹
⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹
⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫺ ⫹ ⫺
⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹ ⫹‡ ⫺ ⫺ ⫺
⫺ ⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺
⫺ ⫺ ⫺ ⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺
⫹ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺ ⫺
E, Epidermal; F, follicular; I, infiltrative; N, nodular; NF, nodular with follicular differentiation; ⫹, present; ⫺, absent. *Nasal tip. † Right side of nose. ‡ Amyloid present.
slowly enlarging, gaping pore with or without central keratinaceous debris, which escapes detection as a BCC (Fig 2). Because lesions of this type do not resemble or act like any other BCC, their identification can be overlooked even by the most experienced physician. We believe that many of these lesions can begin as a cluster of small pores with central plugging (Fig 3), which in time develop into a single patulous stellate pit or pore with or without a central keratinaceous plug (Fig 2). Eventually, these lesions may develop a collarette of slightly indurated, yellow-colored and wax-like textured skin that forms the ridged shoulders of the pore ostium, which usually contains keratinaceous debris in its center (Figs 4 and 5). Patients who have had many BCCs treated over a long period may doubt that these lesions are BCCs. They may even resist biopsy and treatment, because the large-pore BCC can be present for many years, demonstrating virtually no change or growth. In our experience, 3 patients with histories of multiple skin cancers initially refused a biopsy of their large-pore BCCs. One patient (patient 2) was followed up for 6 years before consenting to a biopsy (Fig 4); another (patient 4), for 6 months (Fig 5); and the third (patient 6), for 4 months. Also, another two of the large-pore BCCs were identified only after they were excised. Before surgery, they were thought to be epidermoid cysts (Fig 3). However, after routine microscopic examination, they were found to be BCCs with follicular differentiation. Table III summarizes the 12 clinical features frequently observed in the 10 patients who had, in the center of their faces, a BCC that appeared as a large pore.
Fig 1. Biopsy specimen (from patient 10) shows a central follicle with a dilated follicular orifice from which nests and lobules of basaloid cells emanate (A). A closer view shows lobules of cytologically atypical basaloid cells forming small buds with peripheral palisading, absence of retraction spaces, and a cellular stroma (B). (A and B, Hematoxylin-eosin stain; original magnifications: A, ⫻10; B, ⫻20.)
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Fig 2. Patient 5 had, for many years, a typical stellate pit that was a large-pore BCC on the dorsal tip of his nose, measuring less than 5 mm in diameter (arrow).
Fig 3. Right lateral view of patient 5, 1 month after Mohs micrographic surgery done for the large-pore BCC on the tip of his nose. A second large-pore BCC can be seen on the right side of his nose, presenting as a cluster of plugged pores measuring less than 5 mm in overall diameter (arrow). This second large-pore BCC, which was present for a shorter period, was mistaken for an epidermoid cyst. Its true identity was discovered only after surgery, when the pathology report revealed a BCC.
Even though mention of the clinical existence of large-pore BCCs can be found in the current literature,5,6 an exact reference to these lesions could not be identified (R. A. Schwartz, MD, telephone communication, February 1999). However, there ap-
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pears to be a correlation between the characteristic clinical presentation of the large-pore BCC and its histopathologic structure. Carlson-Sweet et al7 recently made reference to a trichoid BCC found in a dilated pore on the nose but identified the BCC as appearing within a dilated pore of Winer. Routine microscopic examination of skin biopsy specimens from the 10 patients with 11 large-pore lesions all revealed a BCC with some degree of follicular differentiation. The criteria used to identify follicular differentiation included the presence of small and large keratin cysts lined by cornified cells, resembling follicular epithelium, and cords or buds of basaloid cells, forming structures reminiscent of follicular bulbs or papillary mesenchymal bodies. In addition, retraction spaces were absent in most cases, and the stroma was cellular. Of particular interest was the histologic presence of either a follicular plug within the BCC or tumor cells arising from follicular ostia in the superficial portion of the BCC. This correlated well with the clinical presentation of the original large-pore lesion, whether it was a lesion with one large central pore or one with a clustered group of small pores (Figs 2, 3, and 4). In some cases, only a small remnant of the follicle was seen, whereas in others, tumor cells were clearly emanating from a central follicular structure. This was interpreted as being partly due to the method by which the original diagnostic biopsy specimens were obtained. Full-thickness punch biopsy specimens encompassed the entire central core of the lesion, providing a more complete view of the overall structure of these large-pore BCCs. In shave biopsies, on the other hand, only small superficial portions of the lesion were removed, providing an incomplete view of the overall structure of the large-pore BCC. The histologic differential diagnosis of a largepore BCC includes various types of adnexal tumors showing follicular differentiation. However, most, if not all, of them usually appear clinically as nodular lesions. Most prominent among these would be trichofolliculoma, trichoepithelioma, and trichoblastoma.8 Clinically, a trichofolliculoma commonly appears as a nodular lesion. On histologic examination, well-differentiated, hair-producing secondary hair follicles are seen arising from a central follicular orifice, which contains multiple vellus hairs emanating from it. In large-pore BCC, buds of atypical basaloid cells do not form well-differentiated follicles. A trichoepithelioma usually presents clinically as a well-circumscribed nodular lesion. On histologic examination, well-circumscribed lobules of basaloid cells forming small cysts and papillary mesenchymal bodies are frequently seen in the upper dermis. The stroma is cellular, closely approximated to the tumor
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Fig 4. Patient 2 had a typical large-pore BCC of the left lower melolabial sulcus present since early adulthood. A BCC (arrow) was clinically diagnosed in September 1987 (A), but the patient refused a biopsy or treatment. Same lesion (arrow) as it appeared in 1989 (B) and then in September 1993 (C) before biopsy and Mohs micrographic surgery (arrow). Same lesion (arrow) in September 1993 (D) with the cheek retracted laterally, revealing the full extent of the patulous pore with its characteristic stellate appearance and yellow, wax-like skin surface changes.
cells, and generally lacks mucin and peripheral retraction spaces. In both large-pore BCC and trichoepithelioma, the stroma is compressed and cellular and lacks peripheral retraction spaces and mucin. Papillary mesenchymal bodies are present but are not as numerous in large-pore BCCs as they usually
are in trichoepitheliomas. Although large-pore BCCs demonstrate a tendency toward follicular differentiation, their basaloid cells show cytologic atypia and are much less well differentiated than the basaloid cells comprising trichoepitheliomas. Appearing as nodules on the skin, some forms of
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Fig 5. Patient 4 had at least 15 other BCCs over his face, trunk, and extremities but refused to acknowledge that this lesion on the right side of the upper lip was a BCC. This long-standing large-pore BCC is seen as a patulous stellate pore with a collarette of wax-like skin surface changes (arrow). The pore ostium is devoid of hair and contains keratinaceous debris.
Table III. Twelve clinical features of a large-pore BCC 1. A stellate pit or a cluster of gaping pores 1-5 mm in diameter with or without central keratinaceous debris 2. Older lesions have slightly perceptible or no induration, and their ostia become more patulous with time, acquiring a yellow, wax-like texture 3. Flush with the surrounding, normal-appearing skin 4. No friable, rolled edges, but acutely angled, asymmetrically ridged shoulders surrounding the ostium of the pore 5. No gray, pearly, translucent tissue 6. No telangiectasia 7. No bleeding or crusting 8. Located in the center of the face 9. In men and women with thick sebaceous skin 10. In smokers of tobacco 11. Very slow growing with minimal to no change 12. Present for many years
trichoblastoma can be difficult to distinguish from BCC.9 On histologic examination, trichoblastomas are generally well-circumscribed nodules of basaloid cells, which, unlike trichoepithelioma, are located in the mid to lower dermis or subcutaneous tissue.10 A superficial variant of trichoblastoma has been described, mostly in association with nevus sebaceus of Jadassohn.11 In these lesions, areas of sebaceous differentiation can be found. Different forms of trichoblastoma have been described, depending on the prominence of the stroma present.8
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Tumor cells in a trichoblastoma usually do not arise from preexisting follicular epithelium, as they do in large-pore BCC. Moreover, a large-pore BCC does not have the same type of prominent stroma as seen in trichoblastoma. A recent report suggests a genetic abnormality common to sporadic trichoepithelioma and BCC.12 Deletions at the chromosome locus 9q22.3, which is in the patched gene locus, were seen in 48% of sporadic trichoepitheliomas. This incidence is similar to that of BCC and suggests a common pathway for these lesions. Therefore, it is not surprising that variants of BCC exist, manifesting some form of follicular differentiation, such as those found in a large-pore BCC. In conclusion, all physicians who treat patients in whom skin cancer may develop need to be aware of BCCs presenting as a large pore in the center of the face. On histologic examination, these large-pore BCCs usually manifest some degree of follicular differentiation. We thank Kathleen Kucer, MD, for permission to include one of her patients (patient 10) in this report. REFERENCES 1. Elder D, Elenitsas R, Jaworsky C, Johnson B. Lever’s histopathology of the skin. 8th ed. Philadelphia: JB Lippincott; 1997. p. 729. 2. Sexton M, Jones DB, Maloney ME. Histologic pattern analysis of basal cell carcinoma: study of a series of 1039 consecutive neoplasms. J Am Acad Dermatol 1990;23:1118-26. 3. Emmett AJJ. Surgical analysis and biologic behavior of 2277 basal cell carcinomas. Aust N Z J Surg 1990;60:855-63. 4. Klovekorn G, Klovekorn W, Plewig G, Pinkus H. Giant pore and hair shaft acanthoma, clinical and histopathologic diagnosis. Hautarzt 1983;34:209-16. 5. Schwartz RA. Skin cancer: recognition and management. New York: Springer-Verlag; 1988. p. 57-70. 6. Andrade R, Gumport SL, Popkin GL, Rees TD. Basal cell epithelioma. In: Andrade R, editor. Cancer of the skin: biology-diagnosis-management. Vol 2. Philadelphia: WB Saunders Co; 1976. p. 821-44. 7. Carlson-Sweet KL, Weigand DA, MacFarlane DF. Trichoid basal cell carcinoma found in a dilated pore on the nose. Dermatol Surg 2000;26:874-6. 8. Headington JT. Tumors of the hair follicle: a review. Am J Pathol 1976;85:479-514. 9. Ackerman AB, DeViragh PA, Chongchitnant N. Trichoblastoma. In: Neoplasms with follicular differentiation. Philadelphia: Lee & Febiger; 1993. p. 606-59. 10. Graham BS, Barr RJ. Rippled-pattern sebaceous trichoblastoma. J Cutan Pathol 2000;27:455-9. 11. Kaddu S, Soyer HP, Kerl H. Trichoblastoma arising in nevus sebaceous [abstract]. Am J Dermatopathol 1997;19:429. 12. Matt D, Xin H, Vortmeyer A, Zhuang Z, Burg G, Boni R. Sporadic trichoepithelioma demonstrates deletions at 9q22.3. Arch Dermatol 2000;136:657-60.